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Antiparasitics 2019:Trends, Forecasts and Analysis of the Veterinary Antiparasitics Market

Animal Pharm Antiparasitics 2019 Contents

Agribusiness Intelligence © 2019 IHS Markit www.agribusinessintelligence.informa.com 1

Contents

Executive Summary .................................................................................................................... 7

1. Parasites in Companion and Food Producing Animals ..................................................... 9 1.1 Introduction .............................................................................................................................................. 9 1.2 Dogs ........................................................................................................................................................ 10

1.2.1 Canine ectoparasites ................................................................................................................... 11 1.2.2 Canine endoparasites .................................................................................................................. 15

1.3 Cats ......................................................................................................................................................... 18 1.3.1 Feline ectoparasites .................................................................................................................... 18 1.3.2 Feline endoparasites ................................................................................................................... 21

1.4 Horses ..................................................................................................................................................... 24 1.4.1 Equine ectoparasites ................................................................................................................... 24 1.4.2 Equine endoparasites .................................................................................................................. 26

1.5 Cattle ....................................................................................................................................................... 28 1.5.1 Bovine ectoparasites ................................................................................................................... 28 1.5.2 Bovine endoparasites .................................................................................................................. 32

1.6 Sheep ...................................................................................................................................................... 36 1.6.1 Ovine ectoparasites ..................................................................................................................... 36 1.6.2 Ovine endoparasites ................................................................................................................... 39

1.7 Swine ....................................................................................................................................................... 41 1.7.1 Porcine ectoparasites .................................................................................................................. 41 1.7.2 Porcine endoparasites ................................................................................................................. 41

1.8 Poultry ..................................................................................................................................................... 43 1.8.1 Avian ectoparasites ..................................................................................................................... 43 1.8.2 Avian endoparasites .................................................................................................................... 45

1.9 Fish .......................................................................................................................................................... 47 1.9.1 Piscine ectoparasites ................................................................................................................... 48 1.9.2 Piscine endoparasites .................................................................................................................. 49

2. Antiparasitic Products ..................................................................................................... 50 2.1 Resistance to antiparasitic drugs ............................................................................................................ 52 2.2 Ectoparasiticides ..................................................................................................................................... 54

2.2.1 Organochlorines .......................................................................................................................... 55 2.2.2 Organophosphates ...................................................................................................................... 55 2.2.3 Carbamates ................................................................................................................................. 56 2.2.4 Formamidines.............................................................................................................................. 56 2.2.5 Pyrethrins and synthetic pyrethroids .......................................................................................... 56 2.2.6 Insect growth regulators ............................................................................................................. 57

Contents Animal Pharm Antiparasitics 2019

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2.2.7 Neonicotinoids ............................................................................................................................ 59 2.2.8 Phenylpyrazoles .......................................................................................................................... 59 2.2.9 Spinosyns ..................................................................................................................................... 60 2.2.10 Isoxazolines ................................................................................................................................. 60 2.2.11 Other ectoparasiticides ............................................................................................................... 61

2.3 Anthelmintics .......................................................................................................................................... 61 2.3.1 Benzimidazoles ............................................................................................................................ 62 2.3.2 Imidazothiazoles .......................................................................................................................... 63 2.3.3 Tetrahydropyrimidines ................................................................................................................ 63 2.3.4 Salicylanilides, substituted phenols and aromatic amides .......................................................... 64 2.3.5 Amino-acetonitrile derivatives .................................................................................................... 64 2.3.6 Cyclic depsipeptides .................................................................................................................... 64 2.3.7 Spiroindoles ................................................................................................................................. 64 2.3.8 Miscellaneous endoparasiticides ................................................................................................ 65

2.4 Antiprotozoal treatments ....................................................................................................................... 66 2.4.1 Ionophores .................................................................................................................................. 66 2.4.2 Amprolium .................................................................................................................................. 66 2.4.3 Sulfonamides ............................................................................................................................... 67 2.4.4 Clopidol and quinolines ............................................................................................................... 67 2.4.5 Triazines ...................................................................................................................................... 67 2.4.6 Antiprotozoal vaccines ................................................................................................................ 67

2.5 Endectocides (Macrocyclic lactones) ...................................................................................................... 68 2.5.1 Avermectins ................................................................................................................................ 68 2.5.2 Milbemycins ................................................................................................................................ 70

2.6 Vaccines .................................................................................................................................................. 71

3. Company Profiles ............................................................................................................ 72 3.1 Zoetis ....................................................................................................................................................... 72

3.1.1 Company background ................................................................................................................. 72 3.1.2 Major antiparasitic products ....................................................................................................... 74

3.2 Boehringer Ingelheim Animal Health ...................................................................................................... 76 3.2.1 Company background ................................................................................................................. 76 3.2.2 Major antiparasitic products ....................................................................................................... 78

3.3 Merck/MSD Animal Health ..................................................................................................................... 80 3.3.1 Company background ................................................................................................................. 80 3.3.2 Major antiparasitic products ....................................................................................................... 82

3.4 Elanco ...................................................................................................................................................... 85 3.4.1 Company background ................................................................................................................. 85 3.4.2 Major antiparasitic products ....................................................................................................... 86

3.5 Bayer Animal Health ............................................................................................................................... 88 3.5.1 Company background ................................................................................................................. 88 3.5.2 Antiparasitic products ................................................................................................................. 90

3.6 Ceva Santé Animale ................................................................................................................................ 93 3.6.1 Company background ................................................................................................................. 93 3.6.2 Major antiparasitic products ....................................................................................................... 94

Animal Pharm Antiparasitics 2019 Contents


3.7 Virbac ...................................................................................................................................................... 96 3.7.1 Company background ................................................................................................................. 96 3.7.2 Major antiparasitic products ....................................................................................................... 98

3.8 Dechra Pharmaceuticals .......................................................................................................................... 99 3.8.1 Company background ................................................................................................................. 99 3.8.2 Major antiparasitic products ..................................................................................................... 101

3.9 Vetoquinol ............................................................................................................................................. 101 3.9.1 Company background ............................................................................................................... 101 3.9.2 Major antiparasitic products ..................................................................................................... 103

3.10 Norbook Laboratories ........................................................................................................................... 103 3.10.1 Company background ............................................................................................................... 103 3.10.2 Major antiparasitic products ..................................................................................................... 104

3.11 Bimeda .................................................................................................................................................. 105 3.11.1 Company background ............................................................................................................... 105 3.11.2 Major antiparasitic products ..................................................................................................... 106

3.12 Perrigo ................................................................................................................................................... 107 3.12.1 Company background ............................................................................................................... 107 3.12.2 Major antiparasitic products ..................................................................................................... 108

3.13 Piedmont Animal Health ....................................................................................................................... 109 3.13.1 Company background ............................................................................................................... 109

3.14 Chalante ................................................................................................................................................ 110 3.14.1 Company background ............................................................................................................... 110

4. Future Trends in the Animal Health Industry ............................................................... 111 4.1 Patents and Innovation ......................................................................................................................... 111 4.2 Research and Development .................................................................................................................. 112

4.2.1 Zoetis ......................................................................................................................................... 112 4.2.2 Boehringer Ingelheim Animal Health ........................................................................................ 113 4.2.3 Merck Animal Health ................................................................................................................. 113 4.2.4 Virbac ........................................................................................................................................ 114 4.2.5 Norbrook Laboratories .............................................................................................................. 114 4.2.6 Perrigo ....................................................................................................................................... 114 4.2.7 Piedmont Animal Health ........................................................................................................... 115

4.3 Conclusion ............................................................................................................................................. 115

5. References .................................................................................................................... 116

List of Figures

Figure 1: Annual revenues ($m) for Zoetis (2014-2018) ............................................................................... 74 Figure 2: Annual revenues (€m) for Boehringer Ingelheim (2014-2018) ...................................................... 77 Figure 3: Annual revenues ($m) for Merck Animal Health (2014-2018) ....................................................... 82 Figure 4: Annual revenues ($m) for Elanco (2014-2018) ............................................................................... 86 Figure 5: Annual revenues (€m) for Bayer Animal Health (2014-2018) ........................................................ 89 Figure 6: Annual revenues (€m) for Ceva (2014-2018) ................................................................................. 94

Contents Animal Pharm Antiparasitics 2019


Figure 7: Annual revenues (€m) for Virbac (2014-2018) ............................................................................... 97 Figure 8: Annual revenues (£m) for Dechra Pharmaceuticals (2014-2018) ................................................ 101 Figure 9: Annual revenues (€m) for Vetoquinol (2014-2018) ..................................................................... 103 Figure 10: Annual revenues (£m) for Norbrook Laboratories (2014-2018) ................................................... 104 Figure 11: Annual revenues ($m) for Bimeda Animal Health (2016-2018) ................................................... 106 Figure 12: Annual revenues ($m) for Perrigo (2014-2018) ............................................................................ 108

List of Tables

Table 1: Major external parasites of dogs .................................................................................................... 15 Table 2: Major internal parasites of dogs .................................................................................................... 18 Table 3: Major external parasites of cats ..................................................................................................... 21 Table 4: Major internal parasites of cats ...................................................................................................... 23 Table 5: Major external parasites of horses ................................................................................................. 26 Table 6: Major internal parasites of horses ................................................................................................. 28 Table 7: Major external parasites of cattle .................................................................................................. 32 Table 8: Major internal parasites of cattle ................................................................................................... 36 Table 9: Major external parasites of sheep .................................................................................................. 38 Table 10: Major internal parasites of sheep .................................................................................................. 40 Table 11: Major external parasites of swine .................................................................................................. 41 Table 12: Major internal parasites of swine ................................................................................................... 43 Table 13: Major external parasites of poultry ................................................................................................ 45 Table 14: Major internal parasites of poultry ................................................................................................ 47 Table 15: Major external parasites of fish ...................................................................................................... 48 Table 16: Major internal parasites of fish ...................................................................................................... 49 Table 17: Examples of the major antiparasitic molecules commercialised since 1990 ................................. 51 Table 18: Animal health companies for fiscal 2018 ....................................................................................... 72 Table 19: Bayer best-selling animal health products (€million) ..................................................................... 89 Table 20: Advantage product family .............................................................................................................. 91

Animal Pharm Antiparasitics 2019 Executive Summary


Executive Summary

Products for the treatment and control of animal parasites generate approximately 30% of the total animal

health market, making antiparasitics the single largest segment of this industry. It is also a very dynamic

sector that is constantly evolving to deal with the both the parasitological challenges and commercial pressures

it faces.

Some of the most significant challenges in recent years have been the emergence of resistance to parasiticides,

such as heartworm in the US. With only a single class of preventative currently available, the search for

alternative heartworm treatments is currently a major driver of R&D in the industry.

Climate change is also having an impact on the industry, through changes to the geographical areas where

vector-borne diseases occur. An example of this is the spread of bluetongue disease in the last five years into

areas of northern Europe. This is a reminder of the constantly evolving risks posed by zoonotic diseases.

Most of the antiparasitic agents used in the animal health industry originated in the agrochemical industry. The

animal health industry does not have a tradition of screening for new molecules. Apart from the isoxazolines,

no major new antiparasitic classes have been commercialized in the past twenty years. As a result, most

antiparasitics are now widely available in generic form, and the number of specialist developers of generic

products has grown accordingly. The major animal health companies have responded by increasing the

indications for existing products and developing combination products that have a wider spectrum of activity

than those with a single ingredient.

Other industry trends include the development of slow release formulations such as the Long Range®

technology used to prolong the administration of eprinomectin to cattle, or the polymer matrix used in the

Seresto® collars and the development of formulations that are easier to administer, such as spot-on treatments

for cats, and flavoured chews for dogs.

The industry itself has seen a lot of changes recently as it goes through a period of consolidation. This has

resulted in the spin-off of a number of the major animal health companies, such as Zoetis, Novartis, Elanco, and

soon Bayer, from their parent companies, and the merger of Boehringer Ingelheim and Merial. There have also

been numerous acquisitions of smaller innovative entities, such as Nexvet Biopharma and Aratana

Therapeutics, as the major players seek to expand their product pipelines.

The growing restriction on the use of antibiotics has seen a shift in emphasis within the animal health industry

towards prevention rather than treatment of animal diseases. Companies such as Elanco and Vetoquinol have

adopted deliberate policies to reduce their dependence on the revenue from antibiotics, as the industry turns

increasingly towards vaccination, which is regarded as the obvious alternative.

The development of vaccines that are effective against heartworm, fleas, ticks and protozoa is regarded as a

long-term goal in the antiparasitics sector of the industry.

Executive Summary Animal Pharm Antiparasitics 2019


The purpose of this report is to provide an overview of the antiparasitics sector of the animal health industry as

it currently stands.

Chapter 1 provides a comprehensive introduction to the different types of parasites that affect dogs, cats,

horses, cattle, sheep, pigs, poultry, and farmed fish.

Chapter 2 details the history and chemistry of the agents that are used for the treatment of parasitic infections.

Also included in this chapter is a section on innovations and patent activity, which gives some indication of

what may emerge from product pipelines over the coming years.

Chapter 3 profiles some of the major companies that are active in the field of antiparasitics today. It includes

some of the major animal health companies, generic specialists and innovators. For each company, a summary

of their M&A history is provided and details of their current product portfolio.

Chapter 4 provides a summary of recent patent applications and research and development activity in the

animal health industry, and some projections for the future of antiparasitic products.

Animal Pharm Antiparasitics 2019 Chapter 1


Table 1: Major external parasites of dogs

Parasite Species Common name(s)

Fleas Ctenocephalides canis Ctenocephalides felis

Dog flea Cat flea

Mosquitoes e.g. Aedes aegypti Mosquitoes

Sandflies e.g. Phlebotomus spp. Sandflies

Lice Trichodectes canis Linognathus setosus Lice

Ticks e.g. Rhipicephalus spp.Ixodes spp.Dermacentor spp.

Brown dog tick Castor bean tick/deer tick Marsh tick

Mites

Demodex canis Sarcoptes scabiei Cheyletiella yasguri Otodectes cynotis

Demodectic mange Sarcoptic mange Cheyletiellosis/walking dandruff Ear mites

Source: The Merck Veterinary Manual, www.parasitipedia.net and www.ESCCAP.org

1.2.2 Canine endoparasites

Internal parasites can affect dogs of any age and breed and include protozoa and a wide range of helminths

such as nematodes (intestinal: roundworms, hookworms and whipworms; non-intestinal: heartworms and

lungworms) and cestodes (intestinal: tapeworms). Common endoparasites affecting dogs are outlined below.

Gastrointestinal worms

Roundworms

The large roundworms belonging to a group called ascarids, are the most common gastrointestinal parasites

and include Toxocara canis and Toxascaris leonina. T. canis is a specific parasite of dogs and other canids, with

its counterpart affecting cats and other felines (T. cati). T. leonina can infect both dogs and cats, and in rare

cases infect humans. The adult forms of these species live in the small intestine of the host, and their eggs look

very similar. Most parasitic roundworms have direct life cycles, i.e. the free-living stages do not need an

intermediate host for development but infect their final host directly, where they migrate to their predilection

sites and complete development to adults. A heavily infected animal can pass millions of eggs in the faeces

each day. Roundworms differ in their life cycles and also in the way they are transmitted. For example, T. canis

can be transmitted by ingestion of eggs, by larvae across the placenta or through milk or via ingestion of a

transport or intermediate host, whereas T. leonina is only transmitted through ingestion of eggs or ingestion of

a transport or intermediate host infected with larvae.

SAMPLE



Table 3: Major external parasites of cats


Fleas Ctenocephalides felis Cat flea

Mosquitoes e.g. Aedes aegypti Mosquitoes

Lice Felicola subrostratus Cat lice

Ticks e.g. Rhipicephalus spp. Ixodes spp. Dermacentor spp.

Brown dog tick Castor bean tick/deer tick Marsh tick

Mites

Notoedres cati Demodex cati Cheyletiella blakei Otodectes cynotis

Notoedric mange/feline scabies Demodectic mange Cheyletielosis/Walking dandruff Ear mites

Source: The Merck Veterinary Manual, www.parasitipedia.net and www.ESCCAP.org

1.3.2 Feline endoparasites

Internal parasites can affect cats of any age and breed and include protozoa and a wide range of helminths

such as nematodes (intestinal: roundworms and hookworms; non-intestinal: heartworms) and cestodes

(intestinal: tapeworms). Common endoparasites affecting cats are outlined below.

Gastrointestinal worms

Roundworms

In cats and especially in kittens, the roundworm Toxocara cati is the most common gastrointestinal nematode

which is found worldwide and can also infect humans. The disease caused by T. cati is called toxocariasis.

Roundworms of the species T. cati have a direct life cycle, which is particularly complex as a cat can acquire an

infection through the ingestion of eggs, ingestion of a transport host such as an earthworm or beetle, ingestion

of an intermediate host such as a mouse, or by larvae through the milk. In young kittens, ingested eggs release

the larvae in the intestine, which cross the gut wall and travel to the lungs via the bloodstream. Coughing

assists the larvae to further migrate to the trachea and the mouth. Larvae are then swallowed and mature to

egg-producing adult worms in the small intestine. In older kittens and adult cats, the hatched larvae can

undertake a somatic migration that can lead them to numerous organs (liver, lungs, heart, brain, muscles, gut

wall) where they encyst and start a period of dormancy which can last for years. Parts of these dormant larvae

can migrate back to the gut where they complete development to adult worms and start producing eggs.

Another important roundworm affecting cats is Toxascaris leonina but this is much less common. This

nematode has a simpler direct life cycle. After an animal ingests infective eggs, the eggs hatch in the gut where

the larvae mature before returning to the lumen of the small intestine where they molt to adults.

SAMPLE

Chapter 1 Animal Pharm Antiparasitics 2019


Table 7: Major external parasites of cattle


Biting flies

Haematobia irritans Stomoxys calcitrans Glossina spp. Simulium spp. Culicidae spp.

Horn fly Stable fly Tsetse fly Black fly Mosquitoes

Nuisance flies Musca autumnalis Hydrotaea irritans

Face fly Head fly

Screw-worm flies Cochliomyia hominivorax Chrysomyia bezziana

New World screw-worm Old World screw-worm

Warble flies Hypoderma spp. Cattle grub

Chewing lice Damalinia bovis

Sucking lice

Linognathus vituli Haematopinus eurysternus Solenopotes capillatus Haematopinus quadripertusus

Long-nosed cattle louse Short-nosed cattle louse Little blue cattle louse Cattle tail louse

Ticks

Rhipicephalus (Boophilus) microplus Rhipicephalus spp. Amblyomma spp. Hyalomma spp.

Cattle ticks

Mites

Sarcoptes scabiei (var bovis) Psoroptes ovis Chorioptes bovis Demodex bovis

Sarcoptic mange/scabies Psoroptic mange Chorioptic mange/leg mites Demodectic mange

Source: The Merck Veterinary Manual and www.parasitipedia.net

1.5.2 Bovine endoparasites

Gastrointestinal nematodes are the most important internal parasites affecting cattle in most countries

where they are raised commercially. Lungworms, tapeworms and liver flukes can also affect the health and

productivity of grazing stock. Protozoan parasites such as Neospora caninum and Eimeria spp are also

problematic for producers as well as other animals.

SAMPLE



Table 12: Major internal parasites of swine


Gastrointestinal nematodes

Ascaris suum Hyostrongylus rubidus Physocephalus sexalatus Ascarops strongylina Strongyloides ransomi Trichuris suis Trichinella spiralis

Large roundworm, large white worm Red stomach worm Thick stomach worm Thick stomach worm Intestinal threadworm Whipworm Roundworm

Kidney worms Stephanurus spp.

Lungworms Metastrongylus spp.

Protozoa

Isospora suis Eimeria spp. Cryptosporidium parvum Toxoplasma gondii

Source: The Merck Veterinary Manual and www.parasitipedia.net

1.8 Poultry

1.8.1 Avian ectoparasites

Bedbugs

The common bed bug (Cimex lectularius) is a wingless, bloodsucking insect, belonging to the Hemipterans,

that affects poultry worldwide. Bed bugs do not live on their hosts but hidden in cracks and crevices in their

surroundings. They visit their hosts only for feeding, mainly during the night. When searching for food they will

not only bite housed animals and poultry, but also any other suitable host they may find, including humans.

Bed bugs can survive for up to twelve months without feeding. They can become a serious pest in poultry

houses, particularly in layer and breeder operations. The saliva of bed bugs contains allergens that cause

pruritus in the hosts. The affected birds itch and peck themselves leading to loss of feathers and distress.

They may also develop skin inflammations, particularly in the breast and the legs. Massive infections can cause

anaemia due to excessive blood loss. Bug faeces leave small spots on the eggs that can reduce their value.

Fleas

The sticktight flea (Echidnophaga gallinacea) is a major poultry pest in the subtropical and tropical New World.

It is unique among poultry fleas in that the adults become sessile parasites and usually remain attached to the

skin of the head or anus for days or weeks. Chicken fleas (Ceratophyllus spp) can also become a problem in

poultry houses worldwide, especially in regions where the climate is hot and humid. Heavy flea infestations are

rare but can cause host emaciation and reduced egg production. The Western chicken flea, or black hen flea,

SAMPLE



Apart from the isoxazolines no major new antiparasitic drug classes have been commercialized in the past

twenty years. As a result, most antiparasitics are now widely available in generic form. Instead, the trend in

recent years has been towards developing combination products that have a wider spectrum of activity than

those with a single ingredient, thus giving them a competitive advantage in the marketplace. For instance,

combining an ectoparasiticide and an endoparasiticide, or endectocide in the same product. Combining active

ingredients also helps to combat resistance in the target parasite population. Another means of gaining a

competitive advantage is through increasing the duration of activity of the product. This can be achieved by

either developing active ingredients that have a prolonged residual effect, such as fluralaner; or by developing

slow release formulations for short-acting parasiticides such as the Long Range® technology used to prolong

the administration of eprinomectin to cattle; or the polymer matrix used in the Seresto® collars for

administration of imidacloprid and flumethrin to dogs and cats. Another recent innovation is the use of gelatin

beads to deliver coccidia vaccines more effectively to poultry.

Table 17: Examples of the major antiparasitic molecules commercialised since 1990

Active Ingredient

Class Company Trade name(s)

First launch

Species Main parasite target

Moxidectin Milbemycin Fort Dodge

Cydectin ProHeart

1990 Cattle, sheep, pig, horse, dog, cat

Nematodes, flies, lice, mites, heartworm

Milbemycin oxime

Milbemycin Novartis Interceptor 1990 Dog Heartworm

Lufenuron Benzylurea Novartis Program 1992 Dog, cat Fleas

Doramectin Avermectin Pfizer Dectomax 1993 Cattle, sheep, pig

Nematodes, flies, mites, lice

Fipronil Pyrazole Merial Frontline 1994 Dog, cat Fleas, ticks

Fluazuron Benzoylurea Novartis Acatak 1994 Cattle Ticks

Imidacloprid Neonicotinoid Bayer Advantage 1996 Dog, cat Fleas

Eprinomectin Avermectin Merial Ivomec Eprinex

1997 Cattle Nematodes, flies, mites, lice

Dicyclanil Pyrimidinamine Novartis Clik 1998 Sheep Blowfly

Pyriproxyfen IGR Virbac Bayer

Cyclio Fleegard

1998/ 2001

Dog, cat Fleas

Selamectin Avermectin Pfizer Revolution Stronghold

1999 Dog, cat Heartworm, fleas, ticks, mites, nematodes

Nitenpyram Neonicotinoid Novartis Capstar 1999 Dog, cat Fleas

Spinosad Spinosyn Elanco Elector 2000 Cattle, sheep Flies, lice

SAMPLE



to $2.88bn. Again, the companion animal division (+17% to $1.61bn) outperformed the firm's livestock

business (+2% to $1.27bn). Internationally, the trends were similar. Overall, non-US revenues improved 9% to

$2.89bn, companion animal turnover climbed 18% to $1bn, while livestock sales were up 5% to $1.89bn. Sales

in China and the UK both increased by 21%, while the firm's sales in Brazil dropped 2%. While Brazil remains

Zoetis' largest international market, China has overtaken Canada in second place. Overall, annual sales of

companion animal products increased 17% to $2.61bn and livestock turnover was up 4% to $3.15bn. The

company has also forecasted 2019 revenues of between $6.175bn and $6.3bn. This would make Zoetis the first

animal health business to report annual sales in excess of $6bn.

Figure 1: Annual revenues ($m) for Zoetis (2014-2018)

3.1.2 Major antiparasitic products

Avermectins

Doramectin is an avermectin endectocide brought to the market by Pfizer in the mid-1990s. Sold as Dectomax®,

it was launched in Brazil and Argentina in 1993, was rolled out in Europe during 1994 and 1995 and reached the

US market in 1996. Early introductions were of an injectable formulation for use in cattle, but registrations for

use in pigs and sheep were also secured at an early stage, while a pour-on product for cattle reached its first

markets in 1997.

Along with Fort Dodge’s Cydectin® (moxidectin) brand, Dectomax® represented the first direct competition for

Merial’s Ivomec (ivermectin) endectocide franchise. Dectomax® and Cydectin reached several key markets at

around the same time, prompting a period of fierce competition between the three companies in the large

animal field.

Moxidectin was also developed by Fort Dodge as a small animal heartworm preventative, known as ProHeart,

a tablet formulation for dogs. A slow release injectable form was also launched as ProHeart 6, claiming six

months of efficacy. However, following reports of adverse side effects, it was voluntarily withdrawn by the

manufacturer in the US in 2004. While this did not affect the marketing of the product in other countries such

4,785 4,765 4,888 5,307

5,825

2014 2015 2016 2017 2018

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Figure 3: Annual revenues ($m) for Merck Animal Health (2014-2018)


Fenbendazole

The long-established benzimidazole anthelmintic, fenbendazole, is still one of the main contributors to Merck’s

revenues in the antiparasitic sector. Marketed under the brands, Panacur® and SafeGuard®, it is approved for

use in a broad range of species, covering both livestock and companion animals. The active ingredient has been

available generically since the middle of the 1990s, but Merck’s portfolio sports a large spectrum of different

formulations to keep the original brand attractive. These formulations include drenches and feed premixes for

ruminants, a sustained release bolus for cattle, a water-soluble suspension for pigs and chickens, granules and

palatable suspensions for horses, and granules, pastes and tablet formulations for use in small animals. In

2018, MSD Animal Health gained authorization in Europe for an expanded indication of Panacur® AquaSol

(fenbendazole). The product was originally approved in 2014. Panacur® AquaSol is a water-administered oral

suspension product, which MSD developed using proprietary wet-milling technology – a process that ensures

the product is highly stable, does not require frequent agitation and provides a high level of efficacy and

convenience. In Europe, Panacur® AquaSol is now indicated for the treatment of gastro-intestinal nematodes in

chickens infected with Ascaridia galli (L5 and adult stages), Heterakis gallinarum (L5 and adult stages)

and Capillaria spp (L5 and adult stages).

Other anthelmintics and endectocides

Merck’s livestock worming range includes a number of generic products, marketed in various countries. These

include wormers based on levamisole (Levacur®) and pyrantel (Pyratape®), respectively. The veteran narrow-

spectrum flukicide, oxyclozanide, is also marketed in various countries as a drench for cattle and sheep under

the original brand, Zanil®.

3,454 3,324 3,478

3,875 4,212

2014 2015 2016 2017 2018

SAMPLE



Table 20: Advantage product family

Brand Ingredients Region Initial launch

Advantage Imidacloprid Worldwide 1996

K9 Advantix

Imidacloprid/permethrin

North America 2002

Advantix Europe 2004

Fortreon Japan 2005

Advantage Max3 Latin America 2005

Advantage Duo Imidacloprid/ivermectin

Australia 2001

Advantage Heart Japan 2003

Advocate

Imidacloprid/moxidectin

Europe, Australia 2005

Advantage Multi North + Central America, New Zealand

2007

Advantage II Imidacloprid/pyriproxyfen North America 2011

K9 Advantix II Imidacloprid/permethrin/ pyriproxyfen

North America 2011

Source: Bayer, Animal Pharm Reports

Another imidacloprid spin-off was launched in 2013 in Europe and North America: the Seresto® flea and tick

collar, containing imidacloprid and flumethrin, which provides protection for 7-8 months. The product

performed well in its initial year and contributed sales of €31m. By the end 2018 this had increased to €52m.

In Australasia, an imidacloprid-based ectoparasiticide is available for sheep: marketed as Avenge®, this pour-on

formulation is indicated for the treatment of body lice (Bovicola ovis).

Other ectoparasiticides

While imidacloprid continues to be the dominant source of Bayer’s revenues in the ectoparasiticides sector,

the company has a number of other ectoparasite control products in its portfolio. However, many of these are

no longer available in certain markets. This is at least in part due to the success of the imidacloprid product

family and the company’s policy to focus on this franchise.

Bolfo®, a propoxur-based flea and tick collar for dogs, is still available in Latin America. In Australia, the

company markets another flea and tick collar for dogs, branded Kiltix® (flumethrin + propoxur). Tiguvon®, which

contains the organophosphate fenthion, is no longer available for pets but is still marketed as a spot-on for

cattle (against ticks, flies, lice and maggots) in Latin America and Australia. Another organophosphate-based

product, Neguvon® (trichlorfon) powder, has all but disappeared, with a dog formulation still available in Italy,

and a livestock and poultry version in some Asian and Latin American markets. A third organophosphate

ingredient in Bayer’s portfolio, phoxim, is still marketed in some European countries under the brands Sebacil®

(for pigs and sheep), and ByeMite® (for poultry).

The cattle pour-on CyLence®, containing cyfluthrin, is a more recent addition to Bayer’s ectoparasiticide

portfolio in countries such as Canada, while the flumethrin-based pour-on product, Bayticol®, is an established

part of the Bayer range in many countries in Europe, Latin America and Asia/Australasia.

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Figure 11: Annual revenues ($m) for Bimeda Animal Health (2016-2018)


In 2013, Bimeda purchased the Praziquantel Injection cestocide from Teva Animal Health through its US

subsidiary. Praziquantel Injection is indicated for the removal of tapeworms in dogs and cats.

In 2015, Bimeda launched LevaMedTM (levamisole hydrochloride) in the US, which is a soluble drench powder

indicated for the treatment of a broad spectrum of parasitic worms in cattle, sheep and swine.

In 2015 Bimeda launched Dectospot (deltamethrin), a topical application for the control of lice and flies on

cattle; ticks, lice, keds and established blowfly strike on sheep; and lice and ticks on lambs. It is licensed for use

during pregnancy and lactation and has zero milk withdrawal in cattle.

In 2016, Bimeda launched Zero in the UK, a soluble granule formulation containing cyromazine 2%. The product

is designed to treat livestock units, including cattle and horse rearing facilities, pig sties and poultry houses, for

the prevention of fly larvae development. It can be applied as dry granules or as a spray or as a pouring solution

after being dissolved in water.

Bimectin® (ivermectin) is available in a variety of formulations including injectables, pour-on and paste for the

treatment of ectoparasites and endoparasites in cattle, sheep, horses and pigs. In 2019, the FDA gave the green

light to Bimeda for its Bimectin® Plus (ivermectin and clorsulon) injectable solution for cattle, which is indicated

for the treatment and control of internal and external parasites. The product is a generic of Merial's Ivomec®

Plus. Other antiparasitics in the Bimeda portfolio include:

Bimeprine® (eprinomectin), a pour-on for roundworms, lungworms, warbles, mites, lice and hornflies in cattle.

Ectofly (cypermethrin), a pour-on for the treatment and control of Blowfly Strike, ticks, lice and headflies on

sheep and lambs.

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220

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2016 2017 2018

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