Comments on FDA's draft guidelines for biosimiliars

This is the second article in the series on Dr. Kantor's comments on biosimilars and regulatory agencies (the first article concerned the European perspective).

Rituparna Chatterjee of the Economic Times published an article titled Biosimilar products development gets a USFDA norms boost but due to editorial constraints, Dr. Kantor's comments were not included. Below you will find the reporter's questions (green) and Dr. Kantor's responses:

"The FDA has a very low threshold that is going to make it very easy to compete in the market."

1. Why do you think this is so?

2. Do giants like Genetech and Biogen stand to gain the most or smaller companies?

3. What does this mean for companies in the space in countries like India/China, etc.?

1. Although the EMA guidelines have been out for a little longer, the FDA was being tight lipped on what their draft guidelines would be. These guidelines set a low clinical bar to demonstrating bio similarity to a reference compound. The question has always been whether a biosimilar would need to do lengthy and expensive clinical testing or whether in vitro (test tube) and preclinical (animal) studies would suffice. The draft guidelines allow for much (but not all) of the testing to be done without the need for large clinical trials. There is an issue, however, of interchangeability vs. biosimilarity -- but it is not entirely clear whether this will be meaningful to payors (and this ultimately drives profits, sales and stick prices). Additionally, biosimilars are allowed to use different formulations from the reference products, thus allowing for more flexibility. These guidelines allow for a case by case analysis and this may give an advantage to certain manufacturers and there is not necessarily a great need to demonstrate clinical biosimilarity in all indications.

2. Giants, like Roche (Genentech has been subsumed by Roche) have built their portfolio in biosimilars, and increased competition may hurt their sales. Analysts have been expecting these draft guidelines for some time, and because of this the stick prices have already adjusted for the lack of perpetual growth. Many of Roche's products continue to have market exclusivity so sales are not expected to be affected for some time (also it will take time for the biosimilars to conduct their studies). There is also the issue of some market exclusivity for the first biosimilar that comes to market, and some companies may be better than others at getting this going.

Other companies, such as Biogen Idec may benefit and be threatened by these new draft guidelines, because it will allow them to both produce their own biosimilars of others' reference products, but also have biosimilar companies produce their branded products, such as Avonex, Tysabri and Rituximab (in collaboration with Roche). Biogen already has the capacity to produce beta interferons for multiple sclerosis (MS), and they could theoretically produce biosimilars of Bayer's Betaseron (and Novartis's Extavia) and EMD Serono's Rebif. The first biosimilars in MS will likely be versions of Teva's Copaxone (glatiranet acetate), though biosimilar Avonex already exists in Iran. Biogen is in a good position because of its rich MS pipeline, and by the time a biosimilar to Avonex hits the market, many patents will already be on Oral BG00012 or injectable Daclizumab and Pegylates Interferon Beta.

Large generic companies, such as Teva and Novartis will benefit from producing multiple biosimilars (such as Lovenox).

A smaller company, with only one product (H.P. ACTHar Gel), Questcor will largely be immune from biosimilars since Te mechanism of action of this product produced from pig pituitary glands is still incompletely understood (and the draft guidelines make it difficult to produce biosimilars in such a case).

3. Indian and Chinese companies have a lot to gain from these draft guidelines, and eventually they will dominate the market, just as they do to some extent in terms of oral generics -- however, the infamous Chinese heparin scare, may make many uneasy and the FDA granted itself a lot of discretion in the approval process of individual biosimilars.

- Dr. Daniel Kantor, MD
Medical Director
Neurologique

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