The FDA sprang a surprise last Friday and approved the first generic exnoxaparin (sanofi’s Lovenox), a low molecular weight heparin. Momenta and Sandoz’ application for this product has been pending for something like five years and although Lovenox was originally approved via the NDA rather than the BLA route (which is why the FDA has been considering the ANDA at all), the conclusions that the FDA reached in approving it (and in simultaneously denying sanofi’s Citizen’s Petition) are also likely to inform its approach to ‘true’ biogenerics.
In its response to sanofi, the FDA laid out the five tests that it used to determine that the Momenta product was equivalent to Lovenox. Put simply, the first three of these were used to determine that the generic looked like Lovenox (using analytical techniquest to show that it had the same structure) while the last two considered whether it also behaved like Lovenox when in the body. From the data submitted by Momenta and Sandoz, the FDA concluded that the generic satisfied these test and could therefore not only be approved but also – crucially – substituted for the originator product.
The fact that the FDA has finally managed to convince itself that it is possible to characterise biologics sufficiently well to establish ‘sameness’ is good news for those companies trying to develop biogenerics, particularly as it holds out the possiblity that biologics could have the equivalent of an AB rating. Judging by the sharp decline in Teva’s share price, investors have also concluded that we are closer to seeing generic versions of Copaxone, Teva’s blockbuster treatment for MS (being developed by Momenta/Sandoz and Mylan and presumably some others as well).
Teva’s own response to the FDA’s announcement was to put out a statement saying a) that it believed that its own version of enoxaparin was also approvable, and, b) that the five tests would not work on Copaxone. Time will tell whether it is right about its enoxaparin, but in our view, Teva’s argument that Copaxone can’t be characterised sufficiently to make an equivalent generic is not entirely convincing. It may have more of a point when it comes to the last two of the FDA’s tests, though. So far, generic companies have been very wary of MS drugs because there is no simple marker that can be used as a proxy for efficacy. Unlike thrombolytics, where activity is both immediate and measurable, the impact of MS drugs is visible only after months of use in patients. It is thus going to be hard for generic manufacturers to satisfy the FDA in the absence of full scale clinical trials, which would be both expensive and lengthy.
Unfortunately for Teva, even if it is right about Copaxone resisting the five tests, its share price will still be vulnerable to investor sentiment. If it wants to prevent this, it should try settlng with Momenta and Mylan, as this would give analysts a firm date for the earliest possible entry of generics and hence remove uncertainty from their forecasts. At the moment, Teva seems to prefer aggressive litigation to peaceful settlement and it would clearly be hard for the company to swallow a deal, as it would effectively mean admitting that a generic Copaxone is possible. However, Momenta and Mylan would have to get their products approved before they could actually take advantage of a settlement and if Teva is correct in believing that they won’t be able to do this, it will have saved itself a lot of money in court fees and still maintained market exclusivity.