BIOSIMILAR: A PURVIEW

IP & Communication

• Biopharmaceuticals such as therapeutic proteins, DNA

vaccines, monoclonal antibodies, fusion proteins, gene

therapy, stem cell therapy, antisense nucleotides, RNA

viruses

• Manufacturing process based on living cells or organisms

which have inherently variable metabolisms

• Large, highly variable & complex molecules in

comparison to the chemical drug (small molecules)

• Fragile nature, biological activity depends upon structural

integrity

• Effective treatment for many diseases

• Expensive

Aspirin - 21 atoms/180 Da

Intact antibody - >20,000 atoms/150, 000 Da

BIOLOGICS

FROM GENE TO PROTEIN: PROCESS TO

PRODUCT

• Gene insert introduced into an expression vector • Recombinant vector transformed/transfectedinto suitable host cell namely prokaryotic or eukaryotic host cell

• Cell culture and scale up of the process to industrial fermentation• Cell culture conditions affect the nature of the end product

• Active drug molecule • Further filtration to remove viral impurities• Sterile and purified product • Analysis of the molecule for uniformity and potency

• Master cell bank established using iterative cell screening and selection process • Working cell banks derived from master cell bank •No two cell banks are exactly alike

Upstream Process Downstream Process

• Mostly involves chromatographic separation & filtration to purify protein molecules• Change in the purification process can affect the clinical characteristics of the product

• Components of the formulation can affect the protein product • Proper storage and handling conditions essential for maintaining integrity and stability

THE BIOLOGICS MARKET

• 10% and 15% of the world pharmaceutical market

• Biopharmaceutical sales

- ~ $108bn market in 2010 from ~ 200

product, 160bn by 2016

- Annual growth rate of 7.8%

-Top 10 products contribute for 50% of the market

• Prime targeted areas - oncology, inflammation, hormones

& growth factors

• Indian prospects

- Major focus: immunobiologics & vaccines

-Target revenue US$5.8 bn by 2012

- Represents a CAGR of 26% & estimated to be

89.1% by 2014

Source: 1. Evaluate Pharma, Newport Premium, IMS MIDAS, Lonza

2. FICCI, “Overview of the Biotech sector in India” (2005)

FOLLOW-ON BIOLOGICS (FOB)

Three types

Biosimilar

Interchangeable

Biobetters

Host cell: Primary factor governing the

nature of protein product

Biosimilar

• Similar versions of innovator biologic drugs approved through

legislative pathway

• Exact copy of the original product impossible due to inherent

complexities

• Follow-on manufacturer has no access to the innovator’s

clone, cell bank, fermentation and purification processes

• Expected Biosimilar: similar in terms of safety, purity and

potency of the product with no clinically meaningful differences

Interchangeable

• Substitutable for innovator drug without the intervention

of health care provider

• Expected to produce same clinical result as the innovator

drug

FOLLOW-ON BIOLOGICS (FOB)

Biobetters

• Biobetters or biosuperiors: improvements to innovator drug

• Second generation biologic

• Enhanced bioavailability or reduced immunogenicity

• E.g. : Glycotope conducting phase I clinical trial for biobetter trastuzumab-TrasGEX

• Clinical studies must demonstrate that switching of the innovator drug

does not result in diminished efficacy or safety in patients

THE BIOSIMILAR OBSTACLE

• Developmental timeline ~ 8 years

• Data requirements & Data exclusivity ~ 12 years

• Clinical safety requirements

• Earlier failure:

- Pharmacokinetics (Pk)

- Pharmacodynamic (Pd)

- Immunogenicity shift

• Regulatory and Marketing approvals – dynamic and evolving

•Timelines pushed: Patent Term Extensions (PTE), Patent Term

Adjustments (PTA), Supplementary Protection Certificate (SPC)

• High price competition due to commercial & manufacturing hurdles

BIOSIMILAR: FUTURE DRIVER

• Increased affordability – major incentive to switch

• ~ 48 biologicals (including blockbusters) to go off-patent in the next two

decades providing impetus to market development

• Branded pharmaceuticals accelerating into biosimilar market

• More pipeline products in later stages of development

• Increased market share & collaboration through

licensing, mergers & acquisitions agreement

• Increased IP valuation & due diligence for

commercialization

• Diverse uptake market – less

regulated approvals

BIOSIMILAR: THE PLAYERS

• Sandoz: first company to push for biosimilar approval

in Europe

• Sandoz launched biosimilar growth hormone,

filgrastim & epoetin

• Teva, Hospira, Ratiopharm: well established biosimilar

companies

• Hospira has an agreement with Celltrion to develop

biosimilar monoclonal antibodies

• Leading Indian Players: Dr. Reddy’s Laboratories, Intas Biopharmaceuticals, Biocon, Wockhardt,

Reliance Life Sciences

• Innovator companies such as Roche, Amgen focusing on biosimilars to protect original brand

• Other companies to join the bandwagon: Stada, Cipla, Boehringer Ingelheim, GE Healthcare,

Samsung with Biogen Idec, Baxter with Momenta

BIOSIMILAR: CURRENT LEGISLATION

• In Europe, Canada & Japan:

Biosimilars approved through a

regulatory pathway

•The EMEA of European Union is

leading in regulation of bisomilar

approval

• In US:

Biosimilar pathway recently implemented in

Feb, 2012 by FDA

• Guidelines provided as Biologics Price

Competition and Innovation Act

(BPCIA)

• In India:

Biosimilar approval is semi-regulated

and no phase I/II studies are required

BIOSIMILAR:

COMPETITIVE INTELLIGENCE

For additional information on various biologics/biosimilars for oncological, inflammatory disorders & the

one serving as immunomodulators write to: admin@scivistaip.com

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