biosimilar - a purview
TRANSCRIPT
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: [email protected]
NEED MORE INFORMATION