Last week, I wrote about the moves of the big pharma multinational companies (MNCs) to increase their presence in the global drug market with “branded generic” drugs (that is, not patent-protected but sold by an MNC with the implication of higher quality). I wondered if the MNCs were also aiming at the public sector market, that is, national health programs with limited budgets and a mandate to provide basic, universal health care, and noted that one Indian generic drug company, Cipla, appears to have that low-margin business in its sights. I glossed over an important point that there are two, distinct categories of drugs involved: chemical-based molecules (easy to duplicate, and, in the US, prove equivalent to the original drug) and protein-based molecules (difficult and expensive to duplicate and tougher to show equivalent). The latter are referred to as biosimilars, since they are products of biological (cell culture) manufacturing processes and therefore each batch made will likely have slight differences (this poses important safety, efficacy, and regulatory questions when the biosimilar is made by different manufacturers). In addition, almost all protein drugs/biosimilars are administered via injection or infusion, often in a hospital setting which limits wider use, although lots of companies are working on alternative delivery technologies. Also, these drugs treat chronic diseases like cancer (e.g., Herceptin, Avastin, Neupogen) and rheumatoid arthritis (Enbrel) although there is one protein drug for treating the symptoms of infection (an antibody, Motavizumab for respiratory syncytial virus by AstraZenceca/Medimmune, Drug Development Technology) and there are peptide (small protein) drugs under development for infectious disease.
The first approved biosimilars were biosynthetic versions of granulocyte-colony stimulating factors (G–CSFs, original drug was Neupogen by Amgen) and there are a handful of big-sellers now or soon off patent (Drug Management Forum):
- 2008-09: BeneFIX, Betaseron, Human Growth Hormone, Humulin, Novolin, Infergen, Intron A, Neupogen, Regrenex
- 2010: NovoSeven
- 2011: Kogenate, Neumega
- 2012: Remicade
- 2013: Avonex, Cerezyme, Humalog, Novolog, Rebif, Rituxan
- 2014: Aranesp, Enbrel, Epogen, Erbitux, Procrit
- 2015: Avastin, Lantus, Neulasta, Sandostatin LAR, Synagis, Tysabri.
The world market for biologic drugs was $130 billion in 2009 and the biosimilars market is estimated to be tens of billions (NY Times article), but the outside the major markets of US/EU/Japan the biosimilar market size is more of a guesstimate. That being said these markets are attracting companies like Amgen, BiogenIdec, and Merck. The head of Merck BioVentures, Mark Kamarck, whom I knew when at Wyeth, said the company has five biosimilars in late-stage trials (Reuters article, Reuters article). And, of course, there are Indian and Chinese companies (Fierce Biotech article) and lots of industry buzz about the US/EU/Japan biosimilar market (e.g., Asia Biosimilar Summit).
Thanks to industry lobbying and political interest in protecting one of the remaining significant US industries, the US market will likely “protected” from biosimilars by the challenging approval path recently promulgated by the US FDA. The EU market is a better target for the biosimilar makers since the European Medicines Agency (EMA) has based its approval on the less-rigorous concept of proving “interchangeability” (Scientific American Guest Blog). So what does the biosimilars fever mean for many those citizens of the world who depend on the pubic sector for treatment of their communicable and non-communicable diseases? Here are my hunches:
- Biosimilars will be used in the public sector in middle income markets first (apparently, Herceptin is already being provided by Mexico’s national health agency despite its high cost, NY Times article);
- The first low-cost biosimilars for the low income countries will be generic insulins because there are a lot under development and the public health savings of their use is substantial;
- Because the non-NMC biosimilar companies will have the experience in selling into the public sector, they will become viable alternatives to the MNCs for biotech companies seeking to license their novel biotherapeutics that may not have large market potential;
- The biosimilar fever will be an impetus for creation of a non- US/EU/Japan regulatory approval pathway similar to that WHO has developed for public sector vaccines; and
- The PDPs (grant-funded programs for developing treatments for neglected diseases) will more get interested in protein therapeutics.
Or fever-induced hallucinations.