the italian pharmaceutical industry

Paolo Barbanti The Italian pharmaceutical industry: trends and business opportunities © 1

Via Placido Riccardi 19 20132 Milano Italy Tel. ++39-02-45409122 / 27203492 Fax ++39-02-27203492

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The Italian Pharmaceutical Industry

Table of Contents

1. OVERVIEW 3

1.1 Bulk Drugs and Pharmaceuticals Products 3

1.2 Production 3

1.3 Italian Imports 3

1.4 Italian Exports 5

1.5 Types of Packages Prevailing in Italy 5

1.6 Pharmaceuticals in Liquid Form 6

1.7 Pharmaceuticals in Solid Form 6

1.8 Various Pharmaceutical Products 7

1.9 Trends and Demographics 7


1.10 Medicines in demand 8

1.11 Dealing with Demographics 9

1.12 Implications for Research 9

1.13 Distribution 11

1.14 Market Structure 11

1.15 New price-setting Models 13

1.16 Changes in Distribution Margins 14

1.17 The Introduction of Generics 14

1.18 Attempts to influence General Practitioner Prescribing 15

2. A SELECTED TARGET OF ITALIAN COMPANIES 17

2.1 Alfa Wassermann 17

2.2 Bouty 25

2.3 Chiesi Farmaceitci 36

2.4 Dompé 41

2.5 Menarini 53

2.6 Recordati 58

2.7 Sigma Tau 68


Overview

Bulk Drugs and Pharmaceutical Products

Production

Italian pharmaceutical sector produces pharmaceutical products and medicine worth 17.6 billion

Euros, and is an important segment in the Italian economy. In recent years, Italian pharmaceuticals

industry has shown a positive trend in development. The average annual growth has been around 5-

6%.

Consumption: Italian consumption of pharmaceutical products is estimated to be about 6.5 billion

Euros (2003).

Most major international pharmaceutical companies have a hold in Italy. These include Roche,

GSK, Pfizer, Novartis, Bayer, Sanofi-Aventis, Lilly etc. They also dominate the Italian

pharmaceutical industry and control about 60 to 65% of the total pharmaceutical trade. While there

are a large number of Italian companies in the pharmaceutical sector, they are relatively small

compared to these multinationals. Italy does not have any homebred large multinational

pharmaceutical company, which could be matched up to the multinationals of USA, Germany,

Switzerland or UK.

Italian Imports

Italian imports include products such as: Acyclic alcohols, Cyclic alcohols, Ethers-peroxide,

Ketone, Quinine, Carboxylic acids, Amino-alcohols, Carboxyamide, Nitrile, Heterocyclic

compounds, Pro-vitamin, Vegetable alkaloids, Antibiotics, Glands, Antis era, Vaccines,

Medicaments, Penicillin and Streptomycin etc.

Details regarding the figures of the Italian import of the last three years are given below:

YEAR Value in Euro (million)

2002 10279.6 2003 10768.8 2004 11349.0


Analyzing the aforementioned figures, it is noticeable, that there has been an increasing trend in

Italian import concerning the said period of time. While in the year of 2002, the Italian import was

worth 10,279.6 million Euros, it increased to 1,349.0 million Euros in 2004. Italian import in 2003

exceeded the import of 2002 by 4.76%, and the import of 2004 exceeded that of 2003 by 5.39%.

About 62% of the total products are imported into Italy are from Switzerland, Germany, U.K,

France and Belgium

Details regarding the import of pharmaceutical products coming from key countries are given

below:

Key Countries Exporting to Italy (2004)

Country 2003 Value in Euro (million)

2004 Value in Euro

(million)

Total Imports 10768.8 11349.0 Switzerland 1727 2079 Germany 1278 1383

United Kingdom 1515 1110 France 1220 1302 U.S.A. 1098 1180

Belgium 821 875

Ireland 1036 988 Netherlands 690 884

Sweden 247 256 Spain 188 265 China 116 114

Denmark 134 145 Austria 38 39

Israel 135 206 Australia 16 13

India 18 14

Market Share in Italian Imports: (Year 2004)

Country Market share in Italian Imports

Switzerland 18.3 Germany 12.9

United Kingdom 9.7 France 11.4 U.S.A. 10.4

Belgium 7.7 Ireland 8.7


Netherlands 7.7

Sweden 2.2 Spain 2.3 China 1.0

Denmark 1.2 Austria 0.3 Israel 1.8

Australia 0.1 India 0.1

Italian Export

Details of Italian Export of Drugs and Pharmaceuticals are given below:

YEAR Value in Euro (million)

2002 10139.6 2003 9740.9 2004 9525.3

During 2003, Italian export decreased by 3.9% comparing to that of 2002. In the year 2004, it was

registered that a decrease of 2.2% in Italian export comparing to that of 2003, took place.

Italian pharmaceutical products are mainly exported to Belgium, Germany, U.K. Switzerland and

USA. They constitute about 60% of the total Italian export of these products.

Types of packages prevailing in Italy

For the pharmaceutical industry, the primary function of packaging remains mainly that of

protecting the product and making it easy and functional to use. To give a clearer picture of the

trends regarding the various types of packaging, some forms are provided below to give the general

idea.


Pharmaceuticals in liquid form

The area of medicines in liquid form includes those taken orally, by injection, as well as ophthalmic

and otological products. The packaging used, therefore, comprises vials and bottles of various sizes.

Of oral liquid products, 30.7% are packed in small or large plastic bottles; 27.4% are packed in

glass objects either glassware containers or glass tubes, and 41.9% are in glass bottles.

Current trends are towards a growth in the use of plastics bottles for syrups, whereas when small

glass bottles are concerned, more container glass is being used, to the detriment of glass tubes.

Where injectable medicines are concerned, the packaging still consists of vials in glass tubes or

small bottles in glass tubes or glass containers. There is a trend in the market towards the use of

freeze-dried products with a consequent increase in the number of small bottles, which obviously

creates a need for vials for sterile water. About 47% of the market is made up of packaging using

vials only, while, approximately 53% of the packaging consists of both vials and small bottles. The

vials are made of glass tube, while the small bottles are both packed in glass containers and glass

tubes.

Regarding liquid pharmaceuticals not taken orally (ophthalmic and ontological products, etc.) there

is a marked trend towards using plastic bottles which account for 94.4% of the entire market, and

small glass bottles account for 5.6% only.

Pharmaceuticals in Solid Form

Approximately 93% of the packaging for solid medicines to be taken orally (tablets, capsules and

soluble powder) is in the form of blister packs. Other important types of packaging are: small

bottles, plastic tubes and bags in bonded materials (paper-aluminum-PE), which have a 4% share of

the entire market. The remaining 3% is made up of rigid aluminium tubes, small glass bottles and

strips of bonded material (card-aluminium-PE).

With regard to powder products for external use, 56.2% of the packaging used is rigid aluminium

tubes, and the remaining 43.8% packages are available in rigid plastic tubes (this field is currently

on the increase).

Products for rectal or vaginal use, depending on their pharmaceutical specialty, are usually in cell-

packs or push-through packs. Plastic materials and thin aluminium foil are also found in this type of

packaging.


Various Pharmaceutical Products

As for creams, gels, etc., about 92.5% of the products are packed in flexible tubes (specifically,

68.5% in aluminium and 24% in bonded material, namely, plastic-aluminium. There seems to be a

slight trend towards the plastic-aluminium option. The remaining 7.5% of this type of

pharmaceutical product is packed in sachets of bonded material (card-aluminium-PE).

The packaging used for spray products is plastic bottles fitted with mechanical dispensers (21.7%)

or the classic metal aerosol (78.3%). The trend towards aerosols, in aluminium or tinned strip, is on

the increase.

Comments and Market Situation:

• Italian pharmaceutical sector manufactures products that worth 17.6 billion Euros and the

average annual growth rate is around 5-6%.

• Most major international pharmaceutical companies like Roche, GSK, Pfizer, Novartis,

Bayer, Sanofi-Aventis, Lilly etc. have a hold in Italy and they control about 65% of the total

pharmaceutical trade in Italy.

• Italy imports bulk drugs and pharmaceutical products that worth 10.2 billion Euros. Around

62% of the total import which enters Italy comes from Germany, Switzerland, France, U.K.

and Belgium (2003).

• Italy exports bulk drugs and Pharmaceutical products the worth of which is 10.1 billion

Euros. About 60% of the total Italian export is mainly sent to Belgium, Germany, U.K.

Switzerland and USA (2003).

• The Italian market of pharmaceuticals is determined by products supplied by large Italian

and foreign multinationals. The foreign multinationals have their own distribution networks

with specialised sale outlets for marketing products at the level of pharmacies, hospitals,

health insurance companies etc. The Italian pharmaceutical industries have similar

distribution networks for the purpose of expanding their sales.


Trends and demographics

In terms of value, Italy’s pharmaceutical market is the fourth largest in Europe and represents

around 13% of the regional total. The continuing demand for pharmaceuticals has put pressure on

the government’s overall funding of healthcare, which stands at around 9% of Gross Domestic

Product (GDP). As has been observed in many other countries, the growth in pharmaceutical

spending has begun to outstrip the growth in total healthcare spending.

Medicines in demand

As a percentage of the total healthcare spending, the current expenditure on pharmaceuticals in Italy

stands at around 22%, which is higher than that of France and Germany – and even the USA.

However, such figures must be examined carefully because although new medicines contribute to

healthcare spending increases in the short term, they can result in net healthcare savings on the long

run because of reduced hospitalization rates, as well as reduced mortality and morbidity.

Globally speaking, Italy is ranked sixth with respect to annual pharmaceutical spending per person

in terms of purchasing power parity (PPP).

Given below are the top six rankings:

Country Pharma-products spending/Person

(EURO per annum)

1. USA 1302 2. JAPAN 568

3. FRANCE 456 4. GERMANY 409

5. UK 365 6. ITALY 304

Pharma-products spending / Person

Products that are in the cardiovascular, alimentary/metabolism, central nervous system, respiratory

and anti-infective therapeutic classes, represent the majority of sales in the Italian pharmaceutical


market. During 2005, these categories represented around 70% of the total pharmaceutical sales in

Italy, which was interestingly paralleled to the distribution pattern in the USA, the leading global

market. There is also a recent rise in sales of dermatology, analgesic, ophthalmology, as well as

cough and anti-influenza products.

Dealing with Demographics

Demographic factors will have a major impact on the make-up of the Italian pharmaceutical market

in the future. Although ageing of the population is affecting healthcare policy in most countries, it is

particularly relevant to Italy since the country may have one of the ‘oldest populations’ in the world

by 2050. This is a result of the fact that the country might have the highest percentage in the world

of population aged 65 and over (18.1%), and the lowest percentage of population aged 15 and

below (14.1%).

This scenario presents the pharmaceutical industry with both opportunities and challenges. On one

hand there will be increased demand for medicines aimed to tackle conditions that predominantly

affect the elderly and this will benefit companies carrying out R&D in these fields. However, in

view of several economic studies that have analyzed the effect of population ageing on healthcare

spending, the government is likely to expand its cost containment approach to healthcare.

It is the changing nature of the demand for healthcare that has prompted the Italian authorities to

develop a more proactive approach to its policies. The recent Italian Sanitary Program (Piano

Sanitario Nazionale) has placed a greater emphasis on preventative measures in healthcare. This

involves preparing a plan for educating people in order to make them understand that changes in

their lifestyle may help them avoid serious medical conditions in the future.

However, the success of such initiatives depends on the government’s ability to have a good

communication with the public together with involving those who provide their healthcare.


Implications for Research

The leading pharmaceutical markets are also major fields for R&D, and Italy is no exception in this

matter. The country is ranked fourth in the world in terms of life sciences R&D spending, and has a

well-organized network of academic and private institutions which are engaged in research projects.

As a result of Italy’s National Health Plan, which focuses on certain priority disease fields, over 250

research projects have been approved so far and these are valued at over 60 million Euros.

Selected Priority Research Areas

� Cardiovascular diseases

� Oncology

� Infectious diseases

� Neurodegenerative conditions

� Immune system disorders

� Molecular medicine and genetic diseases

Italy’s emphasis on an industrial application of this medical research provides an incentive for the

involvement of a large range of pharmaceutical and biotech companies. Italy is already an important

location for clinical trials, with about 600 studies being carried out each year in a variety of

therapeutic areas, and its popularity is likely to increase. In particular, as the target population for

new medicines in future therapeutic areas will often be the elderly, clinical trials will need to reflect

this important part of the population. At present, there are a number of reports that highlight how

the elderly remain under-represented in clinical trials. Thus, the profile of Italy’s population makes

the country an ideal location for clinical trials as for improving this situation. However, much will

depend on the industry’s abilities to communicate with the local medical community and patients to

encourage their involvement in these types of clinical trials. Italy represents an attractive market for


the pharmaceutical industry, because despite the government’s efforts to slow healthcare spending

by targeting pharmaceuticals, there will inevitably be an increase in the demand for new medicines.

The pharmaceutical industry’s challenge is how best to show that use of their products will help

Italy meet its healthcare targets in the long term. The country also represents a vibrant environment

for industry research but this will require companies to demonstrate to the medical community and

patients that their projects have relevance to the healthcare needs of the population.

Distribution

Market Structure

Italy’s NHS allows both private and public pharmacies to coexist. Private pharmacies are owned by

pharmacists who function as independent contractors under the NHS. Public ones, mainly

municipal, are managed by pharmacists employed by the municipality in which the pharmacy is

located. Despite this administrative division, both types of pharmacies are licensed to sell

commercial products and, on behalf of the local health unit, pharmaceuticals. Commercial goods

mainly include bandages, contraceptives, items for personal hygiene, baby products (such as diapers

and infant formula) and cosmetics (some pharmacies also sell homeopathic products).

Pharmaceuticals include drugs and dietary goods and can only be sold if a consumer has a

prescription from a general practitioner.

All the revenue goes directly to the owner of the pharmacy: to the pharmacist if the pharmacy is

private, and to the municipality if the pharmacy is municipal, which then pays a salary to the

pharmacist running the pharmacy.

Pharmacies’ revenue is a percentage, set by law (usually the Finance Act) of the overall price before

VAT: the most recent rate, set in 1996, is 26.7%. This rate does not take into account special


discounts that pharmacies might be able to negotiate with manufacturers. Conversely, local health

units are responsible for reimbursement.

• Pharmacies cater to 86.4% of the total Italian demand; there are 16,642 pharmacies in Italy

and 252 wholesalers.

• Hospitals cater to the balance 13.6 % of the total Italian demand.

The turning-point for Italy’s pharmaceutical sector was 1, January 1994, when Law 537/1993 came

into force. The pressure to contain expenditure and an impressive series of scandals favoured the

most radical change ever in Italy’s pharmaceutical policy. Since 1994, regulatory policies have:

• redefined the positive list;

• implemented a nationwide drug expenditure budget;

• created new price-setting models;

• changed distribution margins;

• introduced generics; and

• attempted to influence the prescribing of general

practitioners.

In 1994, the National Committee for Pharmaceuticals was established. The 1978 positive list was

abolished, and drugs were reclassified into four groups:

• group A: drugs for severe and chronic illness

• group B: drugs of therapeutic importance not included in

group A

• group C: drugs not included in groups A and B

• group H: drugs provided only by hospitals.


Cost-sharing rules were also modified in 1994: for pharmaceuticals in group A, patients pay 1.55

Euro if the prescription includes only one item or 3.10 Euros for more than one item; and for

pharmaceuticals in group B, patients pay only 50% of the price. Consumers pay the whole cost for

pharmaceuticals in group C, which are not covered by the NHS.

The new list was established according to four criteria: 1) clinical efficacy, documented by

evidence-based criteria; 2) risk-benefit balance of the therapy; 3) acceptability of the therapy to

patients; and 4) cost of the therapy.

The National Committee for Pharmaceuticals also introduced caveats for some drugs; these can be

considered guidelines for the use of pharmaceuticals.

New price-setting Models

Pharmacists freely determine the prices of commercial goods; prices for each pharmaceutical

product are fixed centrally through a negotiation process involving the National Committee for

Pharmaceuticals and the representatives of the major pharmaceutical companies. In 1994, the price-

setting system for drugs was modified. The Committee on Pharmaceuticals (CIP Farmaci), the body

charged with regulating drug prices, was abolished, and a year later the Interdepartmental

Committee on Economic Planning (CIPE) announced a new method for determining drug prices

based on cost estimates derived mainly from information from private companies that effectively

replaced the previous one. According to the new system, prices can be freely set without exceeding

the average European price. The average European price was based on the five most sold drugs,

including generics. Only France, Germany, Spain and the United Kingdom were taken into

consideration in deriving the average European price. Foreign prices were converted into Italian

currency based on purchasing power parity (PPP), a price index used for international comparative

studies.

The principle of similarity was adopted to identify the European equivalents of Italian products: the

same active ingredient, the same route of administration, the same or therapeutically comparable

pharmaceutical form and a similar dosage.


The pharmaceutical industry criticized the new model: in particular, restricting the comparison to

only four countries, including generics in calculating the average European price and using PPP. As

a result of the industry’s dissatisfaction, the Interdepartmental Committee on Economic Planning

(CIPE) introduced a sort of reference price in 1996, based on the principle of the same prices for the

same drugs. The basic idea is that products in group A and group B that use the same active

ingredient, have the same method of administration and have the same or a comparable

pharmaceutical form should have the same prices per unit of compound. This pricing mechanism

exists only for products in groups A and B, since the prices for group C pharmaceuticals are freely

established by the private sector.

Further, in 1997, the Interdepartmental Committee on Economic Planning defined a new price

system for innovative drugs authorized by the European Agency for the Evaluation of Medicinal

Products. Prices are set by negotiation between the National Committee for Pharmaceuticals and

private companies, using the following criteria: a) cost–effectiveness; b) foreign prices; c) internal

market forecasts; and d) investment made by the company related to the introduction of a new drug.

Since July 1998, the average European price method (used for non-innovative drugs) has been

modified to include all European countries and current exchange rates.

Changes in Distribution Margins

Controlling public pharmaceutical expenditure also required focusing on pharmacies. Wholesale

and pharmacy margins were traditionally set as a fixed markup on ex-factory prices and have not

varied much during the last 15 years. From 1981 to 1997 the wholesale margin has changed from

8.0% to 6.65% and the pharmacy margin of drug prices excluding VAT from 25.0% to 26.7%

In 1992, a fixed compulsory rebate on pharmacy margins was introduced for products covered by

the NHS. The rebate was initially set as a fixed proportion of the price (2.5% of the price excluding

VAT, and 3% since 1995).

From 1997, pharmacists were forced to apply a discount to products covered by the NHS. Different

discount rates apply to different price ranges to make the pharmacy’s margin regressive (decreasing

with the price). The discount was 3.75% for prices less than 25.8 Euros; 6% for those between 25.8


Euro and 51.6 Euros; 9% for those between 51.6 Euros and 103.3 Euros; and 12.5% for prices equal

to 103.3 Euros or bigger than that.

The Introduction of Generics

Despite all the interest in cost containment, Italy’s authorities have not given generic drugs much

attention. As a consequence, their use is very limited. The 1995 Finance Act introduced the term

generic into legislation. The law provides pricing incentives to promote generics, stating that, if the

product is marketed at a price at least 20% lower than the equivalent speciality, it is automatically

listed in the same co-payment group. Other incentives come from the financial accountability of

regions over health care and the consequent process of management improvement and cost

containment in the local health authorities of the NHS.

Because wholesale and pharmacy margins were traditionally set as fixed mark-ups, this has made

the distribution of expensive drugs more profitable. Since 1997, the pharmacy margin on NHS-

covered products, became inversely related to the product’s price.

However, the regressive effect is still very slight and does not favour the use of generics. As a

matter of fact, the generics market in Italy is still negligible. The latest data show that generics

account for only 3% of all prescribed medicine units which are sold. However, recently as regional

acts passed (Tuscany being one of the most active regions), the aim is now to promote the

prescription of generics by distributing lists of generics among general practitioners and to

encourage them to prescribe generics. These reforms are nevertheless still in their early stages, and

nationwide implementation is far from being accomplished.

Attempts to influence General Practitioner Prescribing

The prescriptions of general practitioners have never been strictly controlled. Only after the series

of scandals affecting the whole pharmaceutical system, the 1992 reform of the NHS created greater

incentives and opportunities for making general practitioners accountable for their prescribing

activities, such as an expenditure budget for each general practitioner and incentives for general

practitioners to achieve this target. The specific impact of each new regulatory measure is difficult

to assess, even though the reclassification of drugs by the National Committee for Pharmaceuticals

substantially affected NHS drug expenditure. In particular, since 1993, the measures described


above have had two main effects. Firstly, they dramatically reduced NHS pharmaceutical

expenditure from 1993 to 1995. The introduction of guidelines from the National Committee for

Pharmaceuticals and the introduction of a nationwide drug expenditure budget largely achieved this

aim. Secondly, much of the reduction in NHS pharmaceutical expenditure resulted by shifting costs

from the public sector to the patients. The demand for drugs is steep: despite an increase in the

prices of drugs in group C, consumption has increased.

Nevertheless, these cost-containment strategies were not long-run manoeuvres but just emergency

measures to stop the never-ending increase of drug expenditure. This could explain why

expenditure increased again rapidly from 1996 to 1999.


A selected target of Italian Companies

ALFA WASSERMANN

A concrete and successful strategy based on commitment to research and development, production

using the modern technologies and an industrial mentality oriented towards internationalization - all

this has enabled Alfa Wassermann to occupy an important place in the international pharmaceutical

business. This is the strategy at the heart of the company's continued development and the success

of its products in various areas. In the prescription pharmaceuticals, Normix® is without doubt the

product which has given the greatest satisfaction. This antibiotic, indicated for the treatment of a

wide range of gastroenteric disorders, is not just a market leader in Italy, but has also been

recognised by the FDA and approved for sale in the USA under the brand name Xifaxan ™.

For the non prescription specialities, Alfa Wassermann can boast Neoborocillina ®, a historic brand

known to all Italian families.

Alfa Wassermann, Inc. is the worldwide leader in the technology of ultra – centrifugation. Its

equipment is used by all the major vaccine manufacturers.

Research has become a keystone in Alfa Wassermann's corporate strategy, responding to the

constant demand for innovation. The result has been pharmaceutical products of great importance

for the growth of the group.

Particularly significant is the success of Sulodexide (Vessel®), a heparinoid with an anti-thrombotic

and profibrinolytic action, and Parnaparin (Fluxum®), a low molecular weight heparin for

prophylaxis and treatment of venous thromboembolism But the most prestigious result of Alfa

Wassermann's research is Rifaximin (Normix®), a topical intestinal antibiotic.

Leader on the Italian market and registered in a number of countries throughout the world,


Rifaximin has also been launched on the USA market after having obtained FDA approval, the

maximum recognition for a drug developed through Italian research.

Salix Pharmaceuticals Inc., the US company responsible for selling Rifaximin under the name

Xifaxan™, is quoted on the American Nasdaq. The Manufacturing Division of Alfa Wassermann is

based in Alanno (Pescara). The modern production and packing plant is equipped with the most

avant-garde technology to guarantee production processes at the highest possible levels covering the

needs of the company and its licensees, the Alanno plant also has a long tradition of contract

manufacturing for third parties.

The Alanno factory is authorised for production by the Italian Ministry of Health and monitored by

regular inspections certifying total compliance with cGMP standards.

In the spirit of and in compliance with this certification, the Quality Control laboratories carry out

regular validation of all the analytical methods used to analyse primary materials and intermediate

and finished products. The Alfa Wassermann production unit at Alanno covers a surface area of

100,000 m² with a covered area of 17,000 m² divided into 11 departments in seven blocks of

buildings. It produces 30 million items per year for Alfa Wassermann and other Italian and

international pharmaceutical companies.

Alfa Wassermann S.p.A. was founded in 1948 and is a consolidated presence on the Italian

pharmaceuticals market, researching, producing and selling both prescription and self-medication

specialities. The headquarters and research laboratories are located at the original premises in

Bologna, while there is a modern production unit at Alanno (Pescara). The International and

Diagnostic Divisions are based in Milan.

Alfa Wassermann SpA promotes its products by means of a network of representatives who visit

general practitioners, specialists and pharmacists as well as public and private laboratories. With a

workforce of over 650 people, the company also acts as a holding company for the group.

One of the strong points of Alfa Wassermann SpA is that more than 60% of turnover is generated

by its own products, developed by in-house research. These include market leaders such as

Normix®, an innovative antibiotic with a topical intestinal activity, discovered and patented by Alfa

Wassermann. Other important specialities are Alfaferone® (Alfa natural interferon) and Fluxum®


(Parnaparin - patented low molecular weight heparin). Alfa Wassermann has also a Division

marketing and selling non prescription specialities with an extensive network of direct promoters to

pharmacies.

The Division owns a wide range of products acknowledged as efficacious and is a market leader in

the oral disinfectant segment with the widely known and appreciated Neoborocillina®. Alfa

Wassermann is also present in the human in vitro diagnostic sector. The Diagnostics Division sells

a wide range of systems and reagents and also distributes the products of leading Japanese and

American manufacturers in Italy.

In 1989, Alfa Wassermann set its own International Division with two main aims - to increase

exports of its speciality drugs by exploring new territories and to promote the international

development of its original products with a network of strategic alliances. Today Alfa Wassermann

operates with a portfolio of 11 products in more than 60 countries throughout the world and an

efficient network of distributors, efficiently backed by an in-house organisation able to provide all

the assistance required. Normix® (Rifaximin) is one of the main products abroad and has

significant growth prospects.

The product internationalization plan is starting to give results. At present, Rifaximin is registered

in 12 countries and in October 2004 the product, under the name Spiraxin®, was introduced into the

market in Spain by Bama-Geve S.L. and another Alfa Wassermann licensee company. But the most

important goal was, without doubt, the launch of the drug on the USA market under the name

Xifaxan™. The results obtained by the International Division include the setting up of Euro

Alliance, a cooperation agreement with other European pharmaceutical companies for research and

development of new drugs.

For more than thirty years, Alfa Wassermann, Inc. instruments and products have been used in

analysis laboratories all over the world for a wide range of diagnostic applications.

These instruments are designed and produced with the aid of the most advanced technology,

guaranteeing the accuracy of the laboratories' analyses.

Currently Alfa Wassermann, Inc. supplies hospital and private analysis laboratories and veterinary

clinics with a line of clinical chemical analysers (ACE Alera) offering a high degree of automation

and reliability.


Alfa Wassermann, Inc. is also leader in separation technology with a line of ultra-centrifuge

equipment used by leading producers of influenza vaccine throughout the world and in other

industrial and research applications. On the basis of its know-how in ultra-centrifuge technology,

Alfa Wassermann, Inc. is designing an innovative instrument which will enable research

laboratories to take great strides forward in the study of proteins and their interaction at a cellular

level.

The production facility is located at West Caldwell (New Jersey-USA) and international sales are

coordinated by the associate company Alfa Wassermann B.V. based in the Netherlands, with a vast

network of distributors.

The globalization of the markets is also affecting strongly the pharmaceutical business. Since the

beginning of the new millennium, Alfa Wassermann reacted to this trend by supplementing its

traditional export activities with a drive to establish its own organization in a number of markets.

This goal has been pursued by the acquisition of local companies or by setting up new subsidiaries.

The new subsidiaries include Alfa Wassermann Polska sp.z o.o., Alfa Wassermann Tunisie s.a.r.l

and Alfa Wassermann (Beijing)Market Research & Management Company Ltd. These are not, of

course, random decisions, but selecting countries whose markets have interesting growth

opportunities.

Acquisitions include the Spanish company Bama-Geve S.L. and the Portuguese BioSaùde- Produtos

Farmacêuticos, Lda., both operating on the Iberian peninsula. BioSaùde is a relatively young

company standing out for its rapid growth, while Bama-Geve is a company with a long tradition on

the Spanish market. Founded in 1909, it has specialized in three areas, dermatology, cardiology and

the hospitals market, with established products such as the historic Linitul® (medicated gauze) and

the more recent Mepentol®, an innovative product for the prevention and treatment of bed sores.

Bama-Geve also sells Alfa Wassermann products such as Tonocaltin®, indicated for the treatment

of osteoporosis and the well-known Rifaximin, which is also becoming established on the Spanish

market under the name Spiraxin®.


At the beginning of 2004, Alfa Wasserman acquired a 35% stake in this company. Farmigea,

founded in 1946, is a pharmaceutical company based in Pisa and specialized in Ophthalmology and

Gynecology. The company manages and oversees all the various steps involved in the manufacture

of its products: from research to production, from providing scientific information to physicians to

marketing and distribution. The manufacturing process now is carried out in a new and state-of-the-

art plant. Farmigea and Alfa Wassermann made the same choice to put Research & Development at

the top of their business strategies and therefore innovative products are being developed

continuously.


Offices and Plants

Alfa Wassermann S.p.A. - Bologna

The "historic" headquarters of Alfa Wassermann are situated in Bologna. Where the Head

Offices, the Research Laboratories and two Divisions:

- the Pharma Division

- the OTC Division

are located too.

Alfa Wassermann S.p.A. Milano

Two Divisions:

- the International Division

- the Diagnostics Division.

Alfa Wassermann S.p.A. - Alanno

The Alanno plant, recently expanded and renovated according to the latest standards, has a

constructed area of over 16,000 sqm divided into 11 sections distributed over 7 blocks.

The warehouse can store up to 3,000 pallets and is equipped with an air-conditioning system

capable of ensuring an even temperature.


BOUTY

Bouty has a strong hold in the Self Care (OTC) with different product dosage forms such as

sedatives, eye drops, analgesics and others; Wound Care - a complete range which differs from the

competitors for the presence of the most innovative haemostatic range on the market; Oral Care –

denture cleaners and adhesives and range of mouthwashes and toothpastes; Home Diagnostics –

early pregnancy and ovulation tests, and Cosmeceutical – products classified as cosmetic and at the

same time considered to have important attention to the curative functions.

Bouty as a reliable distributor, can provide manufacturers without an adequate Italian sales network,

or one of sufficient size, complete Italian market coverage. Bouty boasts of having a professional,

effective sales force in the pharmacy and mass market channels that can function as the

manufacturer's sales and marketing organization.

Products

ALLERGAN – dermatological cream

ASATEX HAIR CARE -anti-hair loss treatment

ASPARTINA – table sweetener

BABY ZANZARA - biological anti mosquitos

products

CALMINE – analgesic

CEROXMED - medication and bandage range


CERULISINA - otological solution

CERULISINA FAST- otological spray

CONFIDELLE PROGRESS – pregnancy and

ovulation test

DAIGO- mineral supplement

DAIGO ENERGY - energy bar

DAIGO MAG- magnesium supplement

DAIGO PROTEIN - proteic bar

DAIGO SPORT - energetic supplement with

mineral and antioxidant vitamins C and E

DEOPED – foot care products

GRAN VISTA – reading glasses

NEO-EMOCICATROL – oinment

NOCTIS - supplement

OCTILIA – eyewash

ODONTOVAX – dental prevention and treatment

ORASIV – denture care products


PEARL DROPS – Whitening toothpastes

PEARL DROPS SMOKERS - 3 in 1 mouthwash

PERILLACTIVE - cream dry and atopic skin

PROPOCAINA - propocitral products

RELAXAR – oinment

SINEGAS – a natural remedy for intestinal gas

VAXITIOL 2 – biological lactobacillus

supplement

VAXITIOL COMB - probiotic + prebiotic

supplement

VERELAIT - laxative

Mass Market

CARE FOR YOU - daily hygiene products for all the family

CEROX EMOSTATICO - medication and bandage range


CEROX ATHLETIC - products for prevention and treatment of home and

sports small accidents

CEROX AROMATHERAPIA - essential oils plasters

CEROX BALSAMICO - essential oils plaster

CEROX PROTECTION- essential oil patch

FIRST RESPONSE - pregnancy and ovulation test

MUDD – clay cleansing masks

PEARL DROPS – Whitening toothpastes

PEARL DROPS OZONE - self cleaning toothbrushes

RIGIDENT - complete range for denture

THERMAE - thermal products range

Drug Delivery of Advanced Technologies

The Drug Delivery System division, through the adoption of modern technologies, develops and

produces different kinds of products:

Trandsermal patches: Transdermal patch technology us away a way in which drugs are released

constantly. Transdermal patches help reducing collateral effects and increase patients’ tolerability of

drugs. The active principle is absorbed gradually, as it acts locally (in the case of topical patches) or

enters body circulation directly (in the case of Transdermal patches with systemic action).


Transdermal Drug Delivery System technology has a wide range of applications: it can be used, for

example, to produce drugs for the treatment of cardio-circulatory diseases, anti-inflammatory, anti

rheumatic, substitutive hormonal therapy and as pain therapy.

Essential oils Patches: the technology adopted for essential oils patches allows patients to inhale

decongestants or natural fragrances without using ointments or sprays. The active principle

evaporates gradually and is inhaled easily by the application of the patch on clothes at the chest

level. It doesn’t stain, doesn’t dirty and has a day-long action.

Oral fast delivery: this kind of technology enables to produce highly bioavailability microfilms,

and allows to immediate release a definite quantity of active principle orally. Oral fast delivery has

a wide range of applications among drugs and medical devices.

Diagnostics

Since 1975, Bouty has developed and manufactured diagnostic products for home and professional

use. Currently, the company is the major player in the domestic diagnostics market for autoimmuno

disease test reagents. In addition, Bouty is considered to be among the leading companies in the

following IVD market sectors:

� ToRCH (Toxoplasma, Rubella, Cytomegalovirus, Herpes panel)

� Syphilis and other STD

� Rheumatology

� Endocrinology

� Bone metabolism markers

� Pancreatic hormones

For some time now, Bouty has pioneered new diagnostic technologies. An example of which was

the Bouty 1994 acquisition of Technogenetics, that brought know-how suitable for:

� development and production of special monoclonal antibodies

� implementation of DNA recombinant techniques

� molecular investigations.


The scientific challenges of the forthcoming era see the company involved in the development of

new products, PCR is based, in the following areas:

� Virology

� Genetics

� Oncovirology

� Immunology

The listed products are the state of the art ones in the infectious disease

testing,


ALFA WASSERMANN


CHIESI FARMACEUTICI

The company, founded in Parma in 1935, is today a dynamic reality in the pharmaceutical market

with global operations consisting of:

� 21 direct affiliates

� 3 manufacturing sites

� 3 research centres.

The Chiesi Group use over 2,700 employees, of whom 300 are involved in research and

development activities.

Chiesi Group has marketing and sales organisations in the majority of European countries: Italy,

France, Spain, UK, Germany, Greece, Austria, Poland, Hungary, Czech Republic, Slovenia,

Slovakia, Romania, Bulgaria and Russia. Italy is the largest market in terms of sales, followed by

France, Spain, UK, and Germany.

In addition to Europe, Chiesi is directly present in Brazil, Pakistan, Morocco, Algeria, Tunisia and

Egypt. In the USA, a small subsidiary is involved in clinical research and regulatory submissions.

Chiesi’s technologies and products are available in over 50 countries through a strategic alliances

network of international pharmaceutical groups developed both on a global and local scale.

Group turnover reached 565 million Euros in 2005.


Chiesi's formula for success is based on a peculiar approach that allows to combine factors often

thought of as opposites in the pharmaceutical industry – such as research and ethics, technology and

humanity, commitment to results and concern for individuals, reliability and empathy – while

encouraging innovation at all levels.


Research is the key to innovation, and according to a recent survey of the European Commission,

Chiesi Farmaceutici is one of the Italian groups with the highest investments in R&D. With

approximately 13-14% of the total turnover invested annually in R&D, Chiesi Farmaceutici is in

line with the largest European pharmaceutical groups.

Through these investments, Chiesi has generated more than 600 patents worldwide and 70% of

sales have come from internal research and development efforts. The Company has currently

collaborations with international research groups and academic centres producing synergies that can

help ensure Chiesi’s future research success.

Chiesi has 3 manufacturing facilities, located in:

� Parma (Italy)

� Blois-La Chaussée Saint Victor (France)

� Santana de Parnaiba (Brazil)

employing approximately 500 individuals.


The manufacturing plant in Parma is an international supply site providing products to over 50

countries. It has been inspected successfully by several Health Authorities, including the USA FDA.

Chiesi Farmaceutici S.p.A. has been ISO 9001:2000 certified for “Research, Development,

Production and Sale of Medicinal Products”.

Specialised departments produce respiratory dosage forms, such as Metered-Dose Inhalers (MDI)

and sterile Unit Dose Vials (UDV) for nebulisation, using the best available “state-of-the-art”

technology, e.g. isolators and Blow Fill Seal aseptic techniques. The production and ancillary

processes (Cleaning in Place, Sterilizing in Place) are driven and monitored through validated

computer systems.

The capacity of new sterile UDV production department is being increased to over 200 million

doses per year. For MDIs, the current capacity is 13 million cans per year, using the HFA

Modulite® technology.

While in the past decade, the Group has grown due to the establishment of new companies in key

European countries, the contribution from Chiesi’s research and development to its“organic

growth” has been highly significant.

The number of “corporate” products is increasing mainly as a result of a number of successful

Mutual Recognition Procedures (MRPs) in Europe and through the obtainement of market

authorizations in several other countries worldwide.

Three units:

� Parma in Italy

� Paris in France

� Rockville in Maryland (USA)

employ over 300 people who work together on very focused drug discovery and development

endeavours in conjunction with major international medical centres.

In 2005, Chiesi invested 71 million Euros in R&D (12.6% of the Group revenues) plus 5 million

Euros in R&D capital expenditures.


The goal of Chiesi is to become a recognised global player in pulmonology and to strengthen the

leadership position in neonatology, both areas in which we have strong competencies and an

established reputation.

To achieve these strategic objectives, the company has focused R&D activities on these two key

therapeutic areas, to maximise the value of internal resources and to reach a critical mass of

approximately 550 million Euros in R&D expenditures from 2006 to 2010.

Based on Chiesi’s proprietary Modulite®, a unique and environmentally-friendly HFA solution

technology for use in metered-dose inhalers - formoterol (Atimos®, Forair®) - was registered and

launched in Europe, and partnered with Novartis.

A fixed combination of formoterol and beclometasone was filed in Germany as Reference Member

State for a following MRP. The anticipated successful launch of this new product (Foster®)may

drive and accelerate the current promising development of carmoterol, a novel potential once-daily

beta-2 bronchodilator as well as its combinations with a steroid and a novel M3 antagonist for the

treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Chiesi also developed,

together with Cambridge Consultants Ltd., a proprietary new-generation dry powder inhaler,

NEXTTM DPI.

This easy-to-use device may be suitable for all types of inhalation products and it may be used with

a DPI formulation of Foster®. The limited, but well focused and organised discovery program in

the respiratory field, has successfully identified interesting new chemical entities for further

development in clinically validated and new molecular targets as potential candidates in COPD, in

collaboration with Italian academic centres. In an effort to focus R&D pipeline, two innovative

CNS projects were out-licensed to Vernalis.


DOMPE’

Dompé is one of the most dynamic, flexible and innovative set-ups on the European scene. A

successful in the traditional pharmaceutical market in the treatment of respiratory and osteoarticular

pathologies, Dompé has also developed its presence in the area of biotechnology with innovative

drugs and services

DRUGS

Dompé SpA

Primary care

• Arial (salmeterolo xinafoato)

• Artrosilene (ketoprofene sale di lisina)

• Fluifort (carbocisteina sale di lisina monoidrato)

• Frivent (teofillina anidra)

• Levotuss (levodropropizina)

• Miotens (tiocolchicoside)

• OKi (ketoprofene sale di lisina)

• Procef (cefprozil monoidrato)

• Prontinal (beclometasone dipropionato)

• Rexalgan (tenoxicam)

• decapinol (delmopinol) - Dispositivo Medico

• Ostenil (sodio ialuronato) - Dispositivo Medico

Aree Specialistiche

• Tobi (tobramicina)

• Provigil (modafinil)

• Actiq (fentanil citrato)

• Remodulin (treprostinil sodio)

Dompé Biotec SpA


• Avonex (interferone β1a)

• Nespo (darbepoetina α)

• Neupogen (G-CSF)

• Neupopeg (pegfilgrastim)

• Parareg (cinacalcet)

• Gliadel (carmustina)

Biogen Dompé


• Tysabri (natalizumab)

Biogen Dompé AG (Svizzera)



RESULTS

Annual sales summary

Draft subject to change. These values do not include intercompany sales

Research & Development

The research & development departments are integrated within Dompé. The core activities include

early discovery, preclinical and clinical development, registration and support to marketing.

R&D is mainly focusing on two major therapeutical fields:

� Immunology/Transplantation

� Oncology.


Immunological Diseases/Transplantation

The major focus of Dompé research is to identify potent and specific inhibitors of pro-inflammatory

chemokines. Chemokines are a large family of small, structurally related proteins that mediate a

wide range of biological activities. Chemokines are essential mediators of normal leukocyte

trafficking but their role is not restricted to cell recruitment but to intervene in a variety of

pathophysiological processes including acute and chronic inflammation, angiogenesis, fibrosis,

infectious diseases and immunological disorders such as rheumatoid arthritis, atherosclerosis,

psoriasis and ulcerative colitis. Chemokines are multipotent cytokines that localize and enhance

inflamation by inducing chemotaxis and cell activation of different types of inflammatory cells

typically present at inflammatory sites. Chemokines and other mediators are secreted also by these

cells. Chemokines exert their functions through the selective binding to one or more seven-

transmembrane spanning, G protein-coupled receptors through which various signals are

transduced. Interleukin 8 (IL-8) is a chemokine that induces chemotaxis of neutrophils and is a

potent angiogenic agent. IL-8 is produced by stimulated monocytes, macrophages, fibroblasts,

endothelial cells, keratinocytes, melanocytes, hepatocytes, chondrocytes and a number of tumor cell

lines. In humans, there are at least two different IL-8 receptor types (type-1 and type-2). The

receptor is a dimeric glycoprotein consisting of 59 kDa and 67 kDa subunit and is expressed in

many different cell types including those which don't respond to IL-8. The receptor density is

approximately 20,000/cell in neutrophils and 300/cell in T-lymphocytes. IL-8 was reported to play a

pathophysiological role in post-ischemia reperfusion injury occurring after kidney, liver, heart or

lung transplantation or after myocardial ischemia or brain stroke. Reperfusion of ischemic tissues

induces the local production of IL-8 which recruits and activates neutrophils that in turn release a

number of tissue-damaging mediators. The discovery by Dompé laboratories of potent inhibitors of

the IL-8 activity has led to a potential innovative therapeutic approach for the treatment of

reperfusional damage and other conditions in which IL-8 is involved. Chemical entities acting as

dual inhibitors of IL-8 and C5a (a fraction of the complement cascade involved in the mechanism of

inflammatory cells recruitment) have been also characterized and contributed to the creation of a

molecular platform for inflammatory and immunological-related disorders. These chemical entities

would broaden the inhibition of inflammation in several pathological conditions which include post-

ischemic reperfusion injury and immunological-related disorders such as psoriasis, ulcerative

colitis, rheumatoid arthritis.


Oncology

The main focus of Dompé is to discover and characterize human recombinant antibodies as

therapeutics mainly for treating neoplastic diseases but is also foreseen the cure of immunological

disorders. This biotechnology platform represents a state of art technology for the characterization,

purification and production of human recombinant antibodies which are gaining more and more

importance in the treatment of neoplastic and immunological diseases as well as in the diagnostic

field. The cloning and expression of human antibodies in E. coli presents numerous advantages over

the cloning and expression in mammalian cells, e.g. no risk for biological contaminants and

production costs are lower. Ovarian cancer has been identified as the principal therapeutic target of

our antibody platform technology. Ovarian cancer cells highly express the α-folate receptor (10-

100 folds the normal cells), thus this receptor represents an ideal therapeutic target. For therapeutic

purposes, in collaboration with the National Institute of Tumors of Milan, a fragment of a human

antibody (Fab) targeting the α-folate receptor (α-FR) present on the surface of most of the ovarian

cancer cells was identified, cloned and expressed in E. coli. The anti α-FR Fab is radiolabelled with

Yttrium and directed against the tumor. A murine monoclonal antibody (MOv 18) directed against

the same epitope and radiolabelled with Iodine has been successfully used in experimental models

in nude mice as well as in patients. In patients, bone marrow toxicity and host immunoreactivity

were the major concerns and represented limiting factors for radioimmunotherapy. A human

antibody Fab fragment would not only markedly reduce the immunogenicity but would also

facilitate the penetration of the radioconiugated antibody in the tumor. The shorter half life of

Yttrium and its deep penetration in tissues represents another additional advantage to the traditional

radiotherapy

COMPETENCES

Research profile

Pharmacology

• In vitro and in vivo models of inflammation, transplantation, respiratory and

cancer diseases.

• Preclinical pharmacokinetics studies in rodents.

Biotechnology


• DNA cloning, phage display, identification and purification of fragments of

human antibodies to be used as therapeutic tool.

Pharmaceutical Development

• Structural, chemical and physical analysis.

• Preformulation and formulation studies (oral, injectable and topical formulations)

stability, scale-up.

Chemistry

• Molecular design, organic synthesis, peptide synthesis.


R & D PROJECTS

Development Pipeline

Pharmaceutical manufacturing

The pharmaceutical plant, designed and constructed by the Foster-Wheeler engineering company,

was inaugurated in 1993 and constitutes the very latest evolution in company production know-

how, which took root at the beginning of the last century. The production facilities are validated

internationally and have a production potential of many tens of millions of units per year of topical

products, oral fluids and solids, combining the highest levels of quality with competitive costs. The

level of supervision of the production activities and the environmental parameters is augmented by

validated computerized systems which conform to the latest GMP standards in current use. The

control of the environmental characteristics of the premises where the storage, dosed distribution

and production activities take place, is carried out on a continuous basis by a DCS System which


makes it possible to gain real time knowledge of differential levels in the pressure, humidity and

temperature to which the processes are subjected. A natural consequence of Dompé’s quest for total

quality has been the certification, obtained in the last two years, relative to the management of the

Quality System ISO 9001 and the Environmental Management System ISO 14001.

Dompé SpA

This Company draws up and provides services of updating and scientific assistance to doctors of

General Medicine, Paediatrics, Pneumology, Otology, Orthopaedics, Rheumatology, Physiatrics,

Odontology, Accident & Emergency and First Aid stations. It guarantees information to the

Pharmacist, both within the hospital and outside, contributing to the development of the citizen's

education in terms of health.

It offers innovative solutions and efficient services to work alongside the National Health Service in

the treatment of respiratory pathologies and osteoarticular disease for the sake of improving the

patient’s quality of life.

THERAPEUTIC AREAS

• Physiatrics

• Cystic Fibrosis

• Sleep Medicine

• Geriatrics

• Infectious diseases

• Internal Medicine

• Sports Medicine

• Odontology

• Orthopaedics and Traumatology

• Otorhinolaryngology

• Paediatrics

• Pneumology

• Emergency

DRUGS


Primary Care

• Arial

• Artrosilene

• Fluifort

• Frivent

• Levotuss

• Miotens

• OKi

• Procef

• Prontinal

• Rexalgan

• decapinol (device)

• Ostenil (device)

Specialist Care

• Tobi

• Provigil

• Actiq

• Remodulin

Dompé farmaceutici SpA

Almost a century after its foundation, Dompé Farmaceutici SpA has now moved into the field of

rare pathologies, with the aim of providing the medical class and the patient with pharmaceutical

products of high therapeutic value, often distinguished by their high technological content. Dompé

farmaceutici declares its express undertaking with regard to Cystic Fibrosis through the distribution

of drugs with a high technological content, through its collaboration with specialist centres and in

the creation of educational projects dedicated to the doctor and the patient.

THERAPEUTIC AREAS

• Palliative Care


Dompé Biotec SpA

Dompé Biotec is exclusively concerned with biotechnological pharmaceuticals of high therapeutic

value. It is the leading company in Italy both in terms of number of biotechnological drugs on the

market and the number of patiets treated.All these drugs are used in specialist fields, mainly in the

hospital setting.

THERAPEUTIC AREAS

• Haematology

• Infectious diseases

• Nephrology

• Oncology

• Transfusion units

• Neuro-Oncology

DRUGS

• Nespo

• Neupogen

• Neupopeg

• Parareg

• Gliadel

Dompé pha.r.ma SpA

Dompé pha.r.ma researches and develops innovative drugs for serious and debilitating pathologies;

it produces medical specialities of its Group and of selected Partners. The goal of R&D is to

improve the quality of life of patients suffering of life-threatening or debilitating diseases. To this

aim, R&D is committed to the discovery and clinical development of innovative drugs.

Dompé International SA

Dompé International was founded in 1997 with the aim of internationalizing Dompé activities by

either boosting international and export sales and by increasing licensing contacts as well as

developing technology exchange with other companies. Dompé International monitors fast


developing markets in order to identify business opportunities in the core business therapeutic areas

of the company.

PARTNERSHIPS

Dompé S.p.A.

• Aziende Chimiche Riunite Angelini Francesco ACRAF S.p.A. - Levotuss

• F.I.R.M.A. S.p.A. - Levotuss

• Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. - Levotuss

• Stada / Ciclum Farma S.A. - Levotuss, Fluifort

• Boehringer Ingelheim Ellas A.E. - Levotuss

• Boehringer Ingelheim Italia S.p.A. - Artrosilene

• Italfarmaco S.A. - Fluifort

• GlaxoSmithkline - Arial

• Bristol-Myers Squibb S.p.A. - Procef

• Roche S.p.A. - Rexalgan

• Schering-Plough Products Inc. - Frivent

• TRB Chemedica S.A. - Ostenil

• Chiron Corporation - Tobi

• Cephalon (UK) Limited - Actiq, Provigil

• United Therapeutics Europe Ltd - Remodulin

Dompé pha.r.ma S.p.A.

Ricerca e Sviluppo

• Biofocus plc

• Bio-Quant Inc.

• Consorzio Interuniversitario Nazionale "Metodologie e Processi Innovativi di Sintesi"

(C.I.N.M.P.I.S.)

• Consorzio per la Costituzione di Milano Ricerche

• Istituto Nazionale per lo Studio e la Cura dei Tumori

• Istituto di Ricerche Farmacologiche "Mario Negri" - Laboratori Negri Bergamo

• Istituto di Ricerche Farmacologiche "Mario Negri" - Milano


• Consorzio Mario Negri Sud

• Università degli Studi di Milano

• Università degli Studi di Torino

• Rega Institute - University of Leuven

• Xoma Ireland Limited

Produzione

• Boehringer Ingelheim Italia S.p.A.

• A. Menarini Manufacturing Logistics and Services S.r.l.

• Roche S.p.A.

Dompé Biotec S.p.A.

• Amgen (Europe) A.G. / Amgen Inc. - Nespo, Neupopeg, Neupogen, Parareg

• Guilford Pharmaceuticals Limited - Gliadel

Biogen Dompé

• Biogen B.V. - Avonex, Tysabri

Biogen Dompé AG (Switzerland)

• Biogen B.V. - Avonex


MENARINI

Menarini was established over a century ago (as many Italian pharmaceutical companies) in a small

laboratory of the Farmacia Internazionale of Naples. In 1915, it transferred to Florence, where it its

head office is still located. Since 1978 Menarini has established a series of agreements with some

important Italian companies: the first agreement was with Malesci which was followed by

agreements signed with Guidotti, Lusofarmaco, Lusochimica and Firma.

The aim of these agreements has been a better organization of the strategic areas of Research and

Development and of Internationalization, as well as reaching maximum efficiency in the chain of

production and supply.

In 1976, activity in the Diagnostics Division was added to the existing ethical drug production and

in 1994 the OTC Division was started.

Today the Menarini Group is the first Italian pharmaceutical group in the world and is present:

� in all countries of the European Union (except the Scandinavian countries)

� in Switzerland

� in Central and Eastern European countries

� in Central America where it ranks at the fifth position

� in the main developing countries such as India, Vietnam, People's Republic of China and

Korea

� in South Africa

� in Argentina (opening of the affiliate from April 2001)

The Group is also present with its own products in over 100 countries in the world using agents and

local distributors.

EUROPE: in addition to Italy where Menarini is the leading pharmaceutical group, sales are

mainly concentrated in Europe: Austria, Benelux, France, Germany, United Kingdom,

Greece, Ireland, Portugal, Spain, Turkey and Switzerland.


CENTRAL AMERICA / LATIN AMERICA: Menarini is present in all Central American

countries and there it is ranked among the top five pharmaceutical companies. Menarini also

has representative agents in Mexico, Colombia, Venezuela, Chile, Ecuador and Peru. The

affiliate in Argentina has been opened in April 2001.

ASIA: Menarini has created a Joint Venture in India and has a representative office in

China. Currently, it is consolidating its presence in the People's Republic of China, in

Vietnam and in South Korea. In other countries, Menarini is represented by agents and

distributors mainly in Bangladesh, Indonesia, Hong Kong, Malaysia, Taiwan and Thailand.

AFRICA and the MIDDLE EAST : In Africa and the Middle East, Menarini's products are

managed by agents and distributors whose promotional activities are controlled by the

Company.

RESULTS

2003

1,802 mill. Euros

51% of this abroad

2004

1,869 mill. Euros

55% of this abroad

2005

2,234 mill. Euros

The Research Activity of the Menarini Group centres on a single pole, Menarini Research, which

deals with all R&D activities from the initial stage of new projects to the registration stage.


The research programmes are divided up among the following centres:

• Florence

• Pomezia (Rome)

• Milan

• Pisa

• Barcelona

• Berlin

and essentially address the following research areas:

� Cardiovascular diseases

� Oncology

� The pain/inflammation/asthma area

Product’s portfolio

The Menarini Group has a hold in the most important therapeutic fields. They are:

� cardiovascular

� gastro-intestinal

� antibiotics respiratory

� anti-diabetics

� anti-inflammatory/analgesics

and many others.


Menarini Diagnostics

The Company was founded in 1976 as a division of A. Menarini Industrie Farmaceutiche Riunite of

Florence, Italy. The average annual growth of the Company turnover for the last four years is

around 16%. In July 1997 A. Menarini Diagnostics was certified by the TÜV Product Service

according to the ISO 9002 and EN 46002. In July 2003, the Company obtained by TÜV the

certification ISO 9001:2000, ISO 13485:2000.. Now, A. Menarini Diagnostics employs

approximately 700 people, 75% of whom are dedicated to marketing, sales, after-sales service and

customer care activities. The 2005 consolidated turnover reached approximately 256 million Euros.

Today, A. Menarini Diagnostics is an International Group and its headquarters are located in

Florence. Additionally, there is an infrastructure made up of ten fully owned subsidiaries in:

� Austria

� Belgium

� France

� Germany

� Greece

� The Netherlands

� Portugal

� Spain

� United Kingdom

� Sweden.

The strategic fields of A. Menarini Diagnostics are:

� Diabetes (self testing & laboratory systems)

� Clinical Chemistry (dry, wet and urinalysis)

� Haematology (blood typing, ESR, cell counting).

� Immunology (immunohistochemistry, autoimmunity, immunometric assays).

Menarini Diagnostics has established a number of successful partnerships with leading producers

including Arkray KDK Corporation (Japan), Inova (USA), Diesse (Italy), CLB (The Netherlands).


Main products and product lines are:

� Glucocard glucose self-testing potentiometric system

� GlucoMen glucose self-testing potentiometric system

� GlucoDay® S continuous glucose monitoring system

� Menagent Easy ready-to-use multipurpose liquid reagents for clinical

chemistry

� Spotchem easy-to-use dry chemistry analyser for Doctor Office and the

veterinary diagnostics.

� Aution Orchestra fully automated urinalysis system

� Vesmatic System automatic system for ESR (Erytro Sedimentation Rate)

measurement

� Ha 8160 fully automated haemoglobin analyser

� Inova a complete program of reagents for autoimmunity.


RECORDATI

Recordati, established in 1926, is a European pharmaceutical group, listed on the Italian Stock

Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), dedicated to the research,

development, manufacturing and marketing of pharmaceuticals, with headquarters in Milan, Italy. It

operates in the main countries Of Europe with a total staff of over 2,000.

A European field force of over 1,000 medical representatives promotes a wide range of innovative

pharmaceuticals, both proprietary and licensed, in a number of therapeutic fields. Recordati’s

current and growing coverage of the European pharmaceutical market makes it a partner of choice

for new product licenses of companies that do not have European marketing organizations.

Recordati is committed to the research of new drug entities within the cardiovascular and urogenital

therapeutic fielss in which its research team has proven scientific competence and a track record of

discovery and development of original drugs. The most recent product is lercanidipine, a latest

generation calcium channel blocker for the treatment of hypertension considered to be the

company’s leading product.

Recordati operates directly in France, Germany, Greece, Ireland, Italy, Portugal, Spain and United

Kingdom. In these countries, it does not only market original pharmaceutical specialties, but it also

promotes innovative in-licensed pharmaceuticals.

Thanks to numerous licensing agreements with international pharmaceutical companies, Recordati's

innovative proprietary pharmaceuticals (lercanidipine, flavoxate, fenticonazole) are distributed in

approximately 100 countries.

Consolidated revenue for 2006 was 576.2 million Euros, operating income was 120.3 million Euros

and the net income was 74.0 million Euros.


Economic & Financial Data

Key Data

(m €)

2002 2003 2004 2005 2006

Net Sales 492.7

(100%)

487.5

(100%)

488.3

(100%)

576.1

(100%)

576.2

(100%)

Operating Income 89.2

(18.1%)

81.0

(16.6%)

90.4

(18,5%)

111.1

(19.3%)

120.3

(20.9%)

Net Income 50.2

(10.2%)

23.7

(4.9%)

54.0

(11.1%)

64.5

(11.2%)

74.0

(12.8%)

Net Sales

Sales by Business


Pharmaceuticals: Net Sales


Key P&L and Cash Flow

(m €)

2002 2003 2004 2005 2006

Net Sales 492.7 487.5 488.3 576.1 576.2

Gross profit

as % of Sales

289.1

58.7%

287.8

59.0%

309.0

63.3%

375.5

65.2%

384.2

66.7%

Operating Income

(EBIT) as % of Sales

89.2

18.1%

81.0

16.6%

90.4

18.5%

111.1

19.3%

120.3

20.9%

Pretax Income 80.7 38.4 86.7 107.0 118.2

Net Income 50.2 23.7 54.0 64.5 74.0

CASH FLOW 84.2 80.5 76.9 89.0 97.3

Per Share Data

2002 2003 2004 2005 2006

Earnings per share (EPS) 0.2525 0.1225 0.270 0.326 0.370

Cash flow per share 0.4225 0.4125 0.387 0.45 0.487


Balance Sheet Structure


Corporate Structure


RESEARCH AND DEVELOPMENT

Drugs are sourced either internally through original research activities or externally through

partnerships with other pharmaceutical companies.

Recordati conducts development activities in the field of cardiovascular diseases; the related

hypertension Recordati’s efforts in this area, led to the discovery of lercanidipine, a latest

generation drug belonging to the widely used calcium channel blocker class.

Zanitek®, a fixed combination of lercanidipine and enalapril and by Recordati, is a new specialty

indicated for the treatment of hypertension developed.

Recordati’s original research is primarily focused on the search for treatments for micturition

disorders. In this field, the researchers at Recordati are working on projects for innovative drugs

that act through new mechanisms of action or on various combinations.

Pipeline

NAME ORIGINATOR INDICATION PHASE

Project S Recordati Chronic Heart Failure

(CHF)

Discovery

2 new projects Recordati Overactive bladder and

Incontinence

Discovery

REC 0035 Recordati Benign prostatic

hyperplasia

Preclinical

REC 2615 Recordati Sexual dysfunction,

female

Reformulation

new

lercanidipine

Recordati Hypertension Formulation


combinations

lercanidipine

MR

Different technology

platforms

Hypertension, general Formulation /

Phase II

pitavastatin Kowa Hyperlipidemia, general Phase III

Stanate® Rockefeller U. / InfaCare Neonatal jaundice,

hyperbilirubinemia

Phase II / III

silodosin Kissei Benign prostatic

hyperplasia

Phase III

prulifloxacin Nippon Shinyaku /

Angelini

Infection, respiratory

tract, urinary tract

Phase III

Infasurf® Ony Calf derived surfactant Pre-filing

fentanyl patch Lavipharm Moderate to severe

chronic pain

Filed in the RMS

(UK)

rupatadine Uriach Rhinitis, allergic,

seasonal / perennial

urticaria

Approved

Zanipress® /

Zanitek®

Recordati Hypertension

(lercanidipine +

enalapril)

Launched in the

RMS (Germany)

RMS - Reference Member State

Manufacturing Facilities

Milan (Italy)

The Group's principal pharmaceutical manufacturing site is in Milan. The premises measure 25,000

square metres, and the plant has a production capacity of 45 million units per year. It specializes in

the manufacturing and packaging of oral solid, drops, injectables and topical formulations. Situated


in Milan and licensed to produce pharmaceutical specialties for the major international markets, the

plant is designed to ensure the highest manufacturing standards in compliance with CGMP (Current

Good Manufacturing Practices) standards; it operates in conformity with the most stringent

international environmental regulations.

Campoverde di Aprilia (Latina, Italy)

The high-tech facility covering an area of over 360,000 square metres, has an installed capacity of

800 cubic metres. In this site, by employing chemical syntheses, active ingredients are produced for

Recordati pharmaceutical brands, and large-scale active ingredients and active ingredients are

manufactured for international markets.

The plant operates in accordance with the cGMP (current Good Manufacturing Practices) and in

conformity with the most stringent international environmental regulations. It is regularly inspected

by the FDA, by other national and international authorities as well as our customers.

The Plant Environmental Management System, has gotten the certification in 2003, according to the

UNI EN ISO 14001: 1996 norm, subsequently confirmed according to UNI EN ISO 14001: 2004

norm. The certification was been released by the International Accredited Unit DNV (Det Norske

Veritas, Italy).

Montluçon (France)

Montlucon in France is the pharmaceutical manufacturing facility of Bouchara Recordati. Covering

an area of approximately 3,500 square metres, the plant is licensed to produce and package oral

liquid, solid formulations and sprays. It has a manufacturing capacity of 20 million units per year.

The plant is designed to ensure the highest manufacturing standards in compliance with GMP

(Good Manufacturing Practices) standards; it operates in conformity with the most stringent

international environmental regulations.

Ringaskiddy, Cork (Ireland)

The site, which covers the area of 4.21 hectares, is located in the pharmaceutical industrial area of

Ringaskiddy, approximately 15km from Cork, the second largest city in Ireland. The lercanidipine


manufacturing facility became operational at the end of 2005. A GMP (Good Manufacturing

Practices) certificate was issued by The Irish Medicines Board in December 2005.

Raw materials

The pharmaceutical chemicals business accounts for 6% of Recordati’s total revenue. Recordati

produces both active ingredients for its own proprietary pharmaceuticals, and active ingredients and

intermediates for the generic drugs market.

Recordati exports around 90% of its production of API’s and intermediates by selling its products

directly to over 50 countries.


SIGMA – TAU

Sigma Tau is one of the most important Italian pharmaceutical groups, it employs 2,366 people and

its corporate turnover in 2005 amounted to € 674 million.

The drive towards internationalization is best testified by the constant development of new

cooperation agreements with many scientific institutes in Europe and North America.


Sigma - Tau is a company whose main objective is to help improve health and the quality of life for

everybody.

To achieve these goals, the company operates in all the clinically important therapeutic sectors and

the huge investments devoted to research - 16% of corporate turnover - are at the basis of its

business

Sigma-Tau employs over 400 researchers, providing them with the means and resources to develop

therapeutic breakthroughs that can better guarantee health conditions for everyone. All this requires

considerable investments.

The Company has opened branches in France, Switzerland, the Netherlands, Portugal, Germany and

other countries in Europe


R & D PROJECTS

ACTIVITIES AND PROJECTS -

Cardiovascular disease, metabolism, oncology, immunology, central and peripheral nervous system.

50 projects, 33 clinical indications studied with 18 molecules of property of Sigma Tau, and most of

which (15) are new and original.

This is the scope and the dimension of internal research, which is carried out in the following

facilities:

� Sigma-Tau Research Centre (Pomezia, RM)

� Prassis Research Institute (Settimo Milanese, MI)

� Tecnogen S.p.A. (Piana di Monte Verna, CE)

� Kenton srl (Pomezia, RM)

� Sigma-Tau Research Inc. (Gaithersburg, MD).


R & D PROJECTS

Therapeutic

Area Drug Indication State of Progress

β4 Thymosin Rip. stasis related

venous wounds and

ulcers

Stage 2 study in

programme*

Istaroxime Heart failure Stage 2**

Rostafuroxin Hypertension Stage 2

Cardiovascular

disease

Propionyl-L-carnitine Intermittent

Claudication

Pre-registration (U.S.A.)

L-carnitine Transplant medicine Stage 2 study in

programme

L-carnitine Peritoneal dialysis Stage 2

Teglicar Type 2 diabetes Stage 2

Metabolism

Propionyl-L-carnitine Dialysis Stage 2; Stage 3 study in

programme

ST 1968 Misc. tumours Preclinical development

Vaccine Misc. tumours Start of clinical trials in

programme

ST 1926 Misc. tumours Stage 1

Gimatecan Misc. tumours (solid) Stage 2#

Acetyl-L-carnitine Chemotherapeutic

neuropathy

Stage 3

Oncology

Defibrotide Occlusive venous

disease

Stage 3 (USA)##

ST 1959 Autoimmune

diseases

Preclinical development

PTX 3 Immunotherapy Preclinical development

Radioimmunotherapy

antibody-guided (PAGRIT®)

Glioma and misc.

tumours

Stage 1

Immunology

Intraoperative avidination Misc. tumours Stage 1


for radiotherapy (IART®)

Propionyl-L-carnitine Intestinal

inflammatory disease

Stage 2 study in

programme

∂1 Thymosin Melanoma, Liver

cancer

Stage 2/3^

∂1 Thymosin Hepatitis C, Hepatitis

B

Stage 3^

DHA/PPQ

(Dihydroartemisinin/Piperaquine)

Malaria Stage 3^^

Patch Ibuprofene Soft tissue

inflammation

Registration

ST 2472 Schizophrenia Preclinical development

ST 1535 Parkinson's Disease Preclinical development

Central

Nervous

System ST 1859 Alzheimer's Disease Preclinical development

ST 983 Liposomial

preparations

Preclinical development

Other

ST 1898 Acne Preclinical development

Cardiovascular disease - Sigma-Tau has discovered and patented Istaroxamine, an innovative

agent (drug) for the treatment of Heart Failure, which is currently in State 2 clinical studies and

object of a research development and in terms of marketing agreement with Debiopharm SA

(Switzerland). Moreover, currently clinical studies are ongoing for a new hypertension treatment

(Rostafuroxime).

Metabolism - Research on type 2 diabetes is currently focussed on developing drugs that can

control glucose levels without causing serious secondary metabolic changes.

Immunology and inflammation - Research on non-steroid anti-inflammatory drugs and molecules

that control the activity of inflammation mediators.


Oncology and immunology - A multiple approach to tumour therapy, recognizing the importance

of research in tumour therapy, and, believing in the importance of trying different therapeutic

approaches, developing research programmes on new antitumour drugs that act by means of

different mechanisms (cytotoxic, antiangiogenetic, cytodifferentiated), on somatic cell therapy

(cancer vaccine) and on a radioimmunotherapy kit. This cutting-edge programme is unique in

placing different approaches and techniques side by side and has produced a wealth of important

data. Of special significance is the work on biotechnologies, and particularly the development of

PAGRIT® (Pretargeted Antibody-Guided RadioImmuno Therapy), based on original tumour-

specific monocloned antibodies which are selectively carried to the tumour. The project, which

originated at the European Institute of Oncology, is being carried out with the participation of

Tecnogen. Among the other projects, a special mention must be reserved for Gimatecan, an oral

antitumor drug belonging to the family of topoisomerase-1 inhibitors, which has been developed in

Italy (University of Milan, Istituto dei Tumori in Milan and Sigma Tau). Gimatecan has been

licensed for co-development by Novartis, a leading concern in oncology research, which has

acquired the worldwide selling rights for the product. The drug is currently in Stage 2.

Central and Peripheral Nervous System –

In neuropharmacology, research at Sigma-Tau follows three main lines:

- the study of molecules that show potential applicability against neurovegetative diseases,

such as Alzheimer's disease, multiple sclerosis or encephalomyielitis;

- the study of new atypical anti-psychotic drugs for the treatment of schizophrenia with

fewer side effects;

- the study of drugs for the treatment of Parkinson's disease which work by a new action

mechanism (A2a antagonists).

An area in which Sigma-Tau is especially proud of its results is the field of rare diseases, the

commitment to rare diseases is underlined by the fact that Sigma-Tau was the fourth company in the

world to obtain the United States Orphan Drug Designation, in 1984, after which it received seven

more; five new designations have been requested from European authorities.

Sigma Tau has recently established cooperation relationships with China which are fully in line

with the Company's approach to the study of natural molecules of particular interest for research. .

Together with the Chinese company Chongqing Holley, the Company has launched a project

directed at internationally registering an anti-malaria drug, in which Sigma-Tau makes its industrial


know-how available in order to guarantee the distribution of the drug in those countries where

malaria still culls millions of victims. In addition, still with Chongqing Holley, as well as with other

Chinese partners, opportunities are being explored to investigate new compounds for the

development in important therapeutic areas, including oncology, making use of the millenary

experience of traditional Chinese medicine.

Another important field of research made by Sigma-Tau is the development of drugs designed for

the treatment of individual patients rather than the disease in general. Hence the study of vaccines

for specific forms of cancer in individual patients, or the development of antihypertensive drugs for

groups of hypertensive patients who share particular genetic features.

FACILITIES:

- Research Centre - Pomezia (RM) - The Research Centre is located at the centre of

Pomezia's industrial estate, marking the importance that Sigma-Tau assigns to the

relations between research and corporate activities. The Research Centre covers

24,000 square metres and hosts approximately 300 researchers. This is where all

drug synthesizing, discovery and preclinical development activities (Pharmacology,

Toxicology, Analytic, etc.) are carried out. The complex also houses the Medical

Supervision and Regulation Affairs offices, which are the divisions involved in

coordinating clinical activities and drug registration worldwide.

- Prassis Research Institute - Settimo Milanese (MI) - The Prassis Research

Institute was created by the Sigma-Tau Group at Settimo Milanese in 1989. The

Institute is divided into two scientific divisions (Chemistry & Analysis,

Cardiovascular Pharmacology) and an Administration Division. The complex was

restored during 1996-1999 to comply with the new legislation on environmental

safety. Research is carried out by a staff of 50 people and is performed in close

coordination with Sigma-Tau's corporate Research and Development structure, of

which the Prassis Institute represents the sector specialised in cardiovascular

diseases.

- Tecnogen - Piana di Monte Verna (CE) - Located in Piana di Monte Verna, in the

province of Caserta, Tecnogen carries out biotechnology research for pharmaceutical

applications, and has acquired specific experience in peptide combinatorial libraries

and pharmaceutical proteins. Tecnogen has recently been authorized to produce

monoclonal antibodies and recombinant proteins for use in clinical experiments.


- Kenton srl - Pomezia (RM) - Kenton is specifically qualified in biotechnologies

applied to the development of methods for the early diagnosis of tumours and of

infections caused by the hepatitis C virus in humans.

- Sigma-Tau Research Inc. - Gaithersburg, MD - The Group's R&S activities are

completed by Sigma-Tau Research Inc., which follows the clinical development of

Sigma-Tau products in the United States. These facilities cover an area of 36,500

square metres. Research activities are often carried out together with the

collaboration of leading academic institutes, many of which are in Italy, such as the

Istituto dei Tumori in Milan, the European Institute of Oncology, and various

universities, including Rome, Milan, Parma, Siena, Brescia and Bari.

PRODUCTS

THERAPEUTIC AREAS

Sigma Tau products include a wide range of products in important

therapeutic areas:

� the cardiovascular and metabolic area includes drugs for the treatment of hypertension,

ischemic heart disease, rhythm disorders, hyperlipoproteinemia and thrombosis.

Cardiovascular drugs include: nitro derivatives, calcium antagonists, ACE-inhibitors,

angiotensin II antagonists, statins, an antiplatelet drug, omega-3 polyunsaturated fatty acids

and bemiparin, a second-generation low molecular weight heparin. In addition, a new drug

is being studied for the treatment of heart failure which is currently in Stage 2 of the clinical

trials; it is a completely new drug that combines lusitropic action with a strong inotropic

effect without increasing oxygen consumption. A new drug is in the development phase for

the treatment of hypertension (Rostafuroxin) which normalizes changes in the tubular

reabsorption of sodium associated with hypertension without interfering with other receptors

involved in regulating arterial pressure or hormonal homeostasis and without inducing the

effects typically caused by diuretics;


SIGMA-TAU PHARMACEUTICALS FOR

CARDIOLOGY

ACESISTEM Enalapril + Hydrochlorothiazide

AMIODAR Amiodarone

DILZENE Diltiazem

ESKIM Polyunsaturated fatty acid ethyl

esters

ESRADIN Isradipine

IVOR Bemiparin

LIBRADIN Barnidipine

LOSAPREX Losartan

LOSAZID Losartan + Hydrochlorothiazide

NAPRILENE Enalapril

NEOPREX Enalapril + Hydrochlorothiazide

NITRO-DUR Nitroglycerine

SIVASTIN Simvastatin

TICLODONE Ticlopidine

the gastroenterology area includes antiulcer drugs, H2 receptor antagonists and proton pump

inhibitors, modulators of intestinal motility and probiotics;


GASTROENTEROLOGY

FAMODIL Famotidine

LIMPIDEX Lansoprazol

VSL#3 Milk enzymes

YOVIS Milk enzymes


� the respiratory area presents innovative products, for the treatment of asthma and

obstructive syndromes of the respiratory tracts, such as an antileukotriene and the

association between beta-2 adrenergic receptor agonists and a corticosteroid;


PNEUMOLOGY

LUKASM Montelukast

SINESTIC Budesonide + Formoterol

� the infectious disease area includes oral and injectable antibiotics, either on their own or in

predetermined associations, that can inhibit the activity of a number of pathogens, and

antiviral drugs for systemic applications;

SIGMA-TAU PHARMACEUTICALS FOR INFECTIOUS

DISEASES

ACTIRA Moxifloxacin

AMPLIUM Ampicillin + Cloxacillin

LORICIN Ampicillin + Sulbactam

SPECTRUM Ceftazidime

TALAVIR Valacyclovir

TENACID Imipenem + Cilastatin

TROZOCINA Azithromycin

VIRUXAN Metisoprinol

� the urologic area offers a drug for the treatment of benign prostatic hypertrophy based on

finasteride, an inhibitor of the enzyme 5-alpha-reductase;


SIGMA-TAU PHARMACEUTICALS FOR UROLOGY

PROSTIDE Finasteride

� the rheumatologic area is represented by etoricoxib, a second-generation COX-2 inhibitor,

a Tenoxicam based Fans, a transdermic preparation (patch) based on Ketoprofene and a

local Felbinac based gel base for symptomatic treatment of osteoarticular and muscle-tendon

pathologies;


RHEUMATOLOGY

DOLMEN Tenoxican

KEPLAT Ketoprofene

TAUXIB Etoricoxib

TRAXAM GEL Felbinac

� in the area of bone metabolism and osteoporosis, we have alendronate, of the

biphosphonates family, a molecule that finds application in the treatment of osteoporosis;


OSTEOPOROSIS

DRONAL Alendronate

� the neurological area, offers a combination for the symptomatic treatment of migraine, as

well as l-acetylcarnitine for use in peripheral neuropathies;



NEUROLOGY

MIGRAPRIM Lysine acetylsalicylate +

Metoclopramide

ZIBREN Acetylcarnitine

� Sigma-Tau recognizes the importance of research in tumour therapy, and, believing in the

importance of trying different therapeutic approaches, has developed research programmes

on new antitumor drugs with different action mechanisms (cytotoxic, antiangiogenic,

cytodifferentiated), on somatic cell therapy (cancer vaccine) and on a radioimmunotherapy

kit.

SIGMA-TAU PHARMACEUTICALS FOR ONCOLOGY

GELCLAIR Polyvinylpirrolidone + Ialuronic acid

+ Glycyrrhetinic acid

NATULAN Procarbazine

TARGRETIN Bexarotene

This cutting-edge programme is unique in putting different approaches and techniques side by side

and has produced a wealth of important data. Of special significance is the work on

biotechnologies, and particularly the development of PAGRIT® (Pretargeted Antibody-Guided

RadioImmuno Therapy), based on original tumour-specific monoclonal antibodies which are

selectively carried to the tumour. The project, which originated at the European Institute of

Oncology, is being performed by the participation of Tecnogen. Among the other projects,

Gimatecan merits a special mention; this is an oral antitumor drug belonging to the family of

topoisomerase-1 inhibitors which has been developed in Italy (University of Milan, Istituto dei

Tumori in Milan). Gimatecan has been licensed for co-development by Novartis, a leading concern

in oncology research, which has acquired the worldwide selling rights for the product. The drug is


currently in Stage 2.

LIST OF PRODUCTS BY BRAND NAMES

LIST OF PRODUCTS BY BRAND NAME

ACESISTEM Enalapril + Hydrochlorothiazide

ACTIRA Moxifloxacin

AMIODAR Amiodarone

AMPLIUM Ampicillin + Cloxacillin

DILZENE Diltiazem

DOLMEN Tenoxicam

DRONAL Alendronate

ESKIM Polyunsaturated fatty acid ethyl esters

ESRADIN Isradipine

FAMODIL Famotidine

GELCLAIR CONCENTRATED

ORAL GEL Polyvinylpirrolidone + Hyaluronic acid + Glycyrrhetinic acid

IVOR Bemiparin

KEPLAT Ketoprofene

LIBRADIN Barnidipine

LIMPIDEX Lansoprazol

LORICIN Ampicillin + Sulbactam

LOSAPREX Losartan

LOSAZID Losartan + Hydrochlorothiazide

LUKASM Montelukast

MIGRAPRIM Lysine acetylsalicylate + Metoclopramide

NAPRILENE Enalapril

NATULAN Procarbazine

NEOPREX Enalapril + Hydrochlorothiazide

NITRO-DUR Nitroglycerine

PROSTIDE Finasteride


SINESTIC Budesonite + Formoterol fumarate

SIVASTIN Simvastatin

SPECTRUM Ceftazidime

TALAVIR Valacyclovir

TARGRETIN Bexarotene

TAUXIB Etoricoxib

TENACID Imipenem + Cilastatin

TICLODONE Ticlopidine

TRAXAM GEL Felbinac

TROZOCINA Azithromycin

VIRUXAN Metisoprinol

VSL#3 Milk enzymes

YOVIS Milk enzymes

ZIBREN Acetylcarnitine

LIST OF PRODUCTS BY ACTIVE INGREDIENT

LIST OF PRODUCTS BY ACTIVE INGREDIENT

Acetylcarnitine ZIBREN

Lysine acetylsalicylate +

Metoclopramide MIGRAPRIM

Alendronate DRONAL

Amiodarone AMIODAR

Ampicillin + Cloxacillin AMPLIUM

Ampicillin + Sulbactam LORICIN

Azithromycin TROZOCINA

Barnidipine LIBRADIN

Bemiparin IVOR

Bexarotene TARGRETIN

Budesonite + Formoterol SINESTIC


fumarate

Ceftazidime SPECTRUM

Diltiazem DILZENE

Enalapril NAPRILENE

Enalapril + Hydrochlorothiazide ACESISTEM

Enalapril + Hydrochlorothiazide NEOPREX

Etoricoxib TAUXIB

Polyunsaturated fatty acid ethyl

esters ESKIM

Famotidine FAMODIL

Felbinac TRAXAM GEL

Milk enzymes VSL#3

Milk enzymes YOVIS

Finasteride PROSTIDE

Imipenem + Cilastatin TENACID

Isradipine ESRADIN

Ketoprofene KEPLAT

Lansoprazol LIMPIDEX

Losartan LOSAPREX

Losartan + Hydrochlorothiazide LOSAZID

Metisoprinol VIRUXAN

Montelukast LUKASM

Moxifloxacin ACTIRA

Nitroglycerine NITRO-DUR

Polyvinylpirrolidone + Hyaluronic

acid + Glycyrrhetinic acid GELCLAIR CONCENTRATED ORAL GEL

Procarbazine NATULAN

Rivastigmine PROMETAX

Tenoxicam DOLMEN

Simvastatin SIVASTIN

Ticlopidine TICLODONE

Valacyclovir TALAVIR


Via Placido Riccardi 19 20132 Milano Italy Tel. ++39-02-45409122 / 27203492 Fax ++39-02-27203492

[email protected]

the italian pharmaceutical industry

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