INNsight article by Peter Wittner, Interpharm Consultancy, November 2010

Do you look at the headline and think – I’ve read all this before? Well, yes, I admit that I have written on the topic before but defend myself on the basis that the US market in general is so significant and Biosimilars market is likely to be huge when it starts to develop.

The legislation to create a biosimilars pathway was passed by the House in February and it is now for the FDA to turn that into a set of guidelines for the industry so the FDA called a meeting for early November at which it wanted input from interested parties about how to frame these guidelines for what it refers to as Section 351(k) applications. This will no doubt give them a headache given its complexity. The issues that it has identified fall into the following categories and it is worth looking at a couple of sections in more detail.

A. Biosimilarity
• Scientific and technical factors that need to be considered
• What range of structural differences between a proposed biosimilar product and the reference product is consistent with the standard ‘‘highly similar’’?
• Under what circumstances should the agency consider finding that animal studies or a clinical study or studies are ‘‘unnecessary’’ for submission of a 351(k)

B. Interchangeability
• What factors should the agency consider in determining whether a proposed interchangeable biological product can be ‘‘expected to produce the same clinical result as the reference product in any given patient?’’
• What factors should the agency consider in evaluating the potential risk related to alternating or switching between use of the proposed interchangeable biological product and the reference product or among interchangeable biological products?

I will spare you the details of some of the other sections, but the broad categories are:

C. Patient Safety and Pharmacovigilance

D. The Use of Supportive Data and Information

E. Definition of a Biological Product
• What scientific and technical factors should FDA consider if it develops a regulatory definition for the category of ‘‘protein’’ (as distinguished from peptide or polypeptide)?
• What scientific and technical factors should FDA consider if it develops a regulatory definition for the category of ‘‘any chemically synthesized polypeptide’’?

F. Guidances
• What types of guidance documents or industry should be a priority for the Agency during the early period of implementation?

G. Exclusivity
• In light of the potential transfer of BLAs from one corporate entity to another and the complexities of corporate and business relationships, what factors should the agency consider in determining the types of related entities that may be ineligible for a period of 12-year exclusivity for a subsequent BLA?
• What factors should the agency consider in determining whether a modification to the structure of the licensed reference biological product results in a change in safety, purity, or potency, such that a subsequent BLA may be eligible for a second 12-year period of marketing exclusivity?

There were other topics such as Transition Provisions and User Fees, but I think that the detail that I have provided above gives some insight into the complexity of the issues that need to be resolved. This is clearly not going to happen overnight as it has taken since February for them to even decide on what are the questions – answers will no doubt take longer. Of course, they could just copy the EMA guidelines, but I would imagine that the FDA would rather adopt the “Not invented here” attitude to them and then go on to reinvent the wheel by themselves!

Anyone hungry for the details of all the issues can find them at
http://edocket.access.gpo.gov/2010/pdf/2010-24853.pdf

In the meantime, one company is already taking advantage of the registration of a biosimilar product albeit through a different route to that which the FDA is now trying to develop. In July, Sandoz announced the introduction in the US of Enoxaparin sodium injection, the first generic version of Lovenox that it had developed in collaboration with Momenta Pharmaceuticals. This has now turned into a major success.

The Sandoz parent Novartis reported US$292m in Enoxaparin revenues for the last nine weeks of the July-September quarter. Sanofi-Aventis in the meantime admitted that its US sales of Lovenox were nearly halved by the launch of the generic, which seems to indicate that hospitals are happy to use the copy. In figures, S-A reported that Lovenox sales in the US fell by 47% to €255m (=$354 million in its third-quarter earnings report in early November.

In the absence of any other generic competitors, it looks like Sandoz will make a killing with this product in the US as long as they can product it fast enough. Jeff George, Novartis’ division head for Sandoz described it as the most successful generic injectable launch ever in the U.S.

This gives a foretaste of what is likely to happen in for other biosimilars if the FDA declares them to be interchangeable which is what has happened in this case.

However, watch out for a potential stumbling block. A congressional committee apparently intends to release a report by the Government Accountability Office claiming that “the FDA risked giving the appearance that it had compromised its integrity during the approval of Enoxaparin.” by approving the Momenta/Sandoz product too quickly. The suggestion appears to be that the FDA benefited from Momenta’s expertise when sorting out the earlier problems with contaminated Heparin and did a favour in return.

Now Teva, with its own version of Enoxaparin still awaiting approval, is suggesting favouritism. Sit back and wait for the fireworks.

Peter Wittner
November 2010
peter@interpharm-consultancy.co.uk
www.interpharm-consultancy.co.uk