The dynamics of the monoclonal antibody (MAb) market have changed significantly over the past two decades. Presently, MAbs generate global revenues of around $20 billion and represent the fastest growing segment within the pharmaceutical industry. This segment is expected to achieve a compound annual growth rate (CAGR) of 14 per cent between 2006 and 2012.
The evolution of antibody technology has acted as a major driver of MAbs market growth, distancing today's blockbuster products from the commercially unsuccessful murine Mabs, which were the primary focus of early-stage antibody development. While chimeric and humanised MAbs currently dominate the market, this technology evolution continues, as the number of fully human MAbs to reach the market increases.
The MAb market was ushered into its 'take off' phase with the launch of Rituxan/MabThera (rituxiMAb) for Non-Hodgkin's Lymphoma (NHL) in 1997. Rituxan/MAbThera represented the first MAb product to succeed commercially in a high-revenue/high-growth market (oncology) and provide significant enhancements in the efficacy of treatment, compared to existing non-MAb therapies.
Buoyed by the rapid success of rituxiMAb, MAb drug developers have proceeded to launch a raft of MAb products in subsequent years, a trend driven by advances in technology allowing for the development of MAbs with higher human composition (known as humanized and fully-human MAbs). Fuelled by key MAb launches - Avastin, Herceptin, Remicade, MAbThera/Rituxan, Humira and Erbitux - the market is presently at an inflection point of maximum sales growth.
Similarly, the labeling of MAbs positioned in the arthritis, inflammation and immune disorders (AIID) market (Remicade and Humira) has aggressively been broadened to include various indications, such as rheumatoid arthritis, crohn's disease, psoriatic arthritis and ulcerative colitis. Furthermore, indication broadening has also spanned
multiple therapy areas with Rituxan/MAbThera approved initially for NHL (oncology) and subsequently for rheumatoid arthritis (AIID). The most recent approval in the antibody segment is Genetech's RanibizuMAb (Lucentis), a humanised IgG fragment produced in E.coli that binds and inactivates VEGA-A, targeted for therapeutic management of neovascular (wet) age-related macular degeneration. This shows a progressive trend towards development of antibody fragments which could be the next logical step ahead of fully humanised monoclonal antibody.
Analysis of the MAb market by company reveals a clear two-tiered structure. Four 'established' players sit at the top end of the market - Genentech, Roche, Abbott and Johnson & Johnson. An additional tier of four 'emergent' players - Biogen IDEC, Amgen, Novartis and UCB Pharma - is also evident.
MAbs - generic market
The exponential growth in the therapeutic monoclonal antibodies segment has been seen for last 4-5 years. Today, anti-cancer monoclonal antibodies segment has a highest contribution in the blockbuster drugs. The opportunities for biosimilar molecules are predicted to increase tremendously in the next decade as several blockbuster drugs are expected to go off-patent. The global market for Indian players appears to be well positioned to leverage their cost-effective operational capabilities and compete on a global platform. With the forthcoming opportunities, Indian biopharma industry has potential to touch the mark of 20 billion in the next decade.
Monoclonal antibodies on fast-track growth
A large number of monoclonal antibodies have already been introduced in India by innovator companies, either through distribution agreements with local companies, or through their own subsidiaries. The MAbs market is becoming a fast-growing segment in India, especially in oncology and auto-immune diseases such as rheumatoid arthritis. Linked to urban lifestyles, arthritis and inflammatory immune disorders are becoming increasingly prevalent. At present only a few therapies for oncology are available and the existing therapies have a high side-effect profile. Due to the technological complexity, monoclonal antibodies development is at a nascent stage in India. However, having recognised the commercial and the therapeutic potential, biopharma companies have begun to take steps for development, either in-house or via collaborations.
India's Biocon has partnered with the innovator for an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody named BioMAb-EGFR, a therapeutic monoclonal antibody based drug for treating tumours of epithelial origin. Biocon launched BioMAb-EGFR in India and is the first of its kind to be clinically developed in the country. The product has shown positive results in trials initiated in various countries and is being studied overseas for its potential use in treatments for lung, colorectal, glioma and pancreatic cancers. In April 2007, Dr. Reddy's Laboratories launched Reditux, the generic version of RituxiMAb, in India at a price 50 per cent lower than the innovator's price. Reditux has the distinction of being the first generic MAb to be launched in the world. Zenotech, a Hyderabad-based biopharma company, has started to build capabilities in the development of monoclonal antibodies. Serum Institute of India is another Indian company which has taken steps towards development of MAbs. The company has entered into an agreement with Akorn of USA for definitive development and exclusive distribution rights for an anti-rabies monoclonal antibody.
MAbs: Trends in India
● Mammalian cell culture with well characterised starting materials
● Serum free cell culture media
● High expression levels
● Preference of CHO over NS0 based MAb
● Microbial systems for MAb fragments
● Manufacturing capacity optimisation
● Strengthen product characterisation
● Strengthen virus removal measures
● Hybrid concepts and disposable manufacturing
● High concentrations in final formulation
● Integrated supply management with strategic partnerships between suppliers, biotechs and CMOs
● Growing economic limitation
- Time and resources
- Substitution and Biosimilars
(The author is Group Leader - Process Development Sciences, Bioprocess Division with Millipore India Pvt. Ltd)