Biotech Values

[dewophile]

copaxone vs lovenox

Because nobody knows exactly how Copaxone works, there is nothing that corresponds to the enox measurement of anticoagulant activity which was part of the FDA enox "sameness" criteria.

you are speaking in absolutes, which is not exactly accurate. enox moa is to a large extent, but NOT completely, due to factor Xa/IIa activity. sandoz CP goes into some detail on the non-factor Xa/IIa activity of the product, some of which can be screened for (and incidentally were not part of the 5 sameness criteria), as well as some activity that, much like copaxone, is poorly understood and for which biomarkers don't exist (e.g. antiinflammatory effects, etc.). just like teva, they use this argument to say clinical trials are necessary to assure equivalence. The FDA didn't disagree with SNY's premise that lovenox moa is not completely understood and biomarkers of activity are imperfect. in fact, if Xa/IIa told the whole story for efficacy why would one need the other 4 criteria? the FDA came to the conclusion in the lovenox case that adding criteria that go to direct molecular structure anaysis, in combination with the biomarkers of activity that do exist, would do the trick to satisfy active ingredient sameness. moreover, since structure of sugars are difficult to characterize, they mandated a series of overlapping structual analyses to add to the biomarker screen.

for copaxone, since the MOA is admittedly even less well understood than lovenox, it would seem the biomarkers that do exist have to be given less weight, and complementary analyses that directly address molecular structure more weight. but in the end, the combination of the two - direct structure analysis and some imperfect (in the case of copaxone less well perfect) biomarker should hopefully do the trick. in addition to easier structural characterization of polypeptides, you don't have to worry about variability that is inherent in a biolobically sourced API like lovenox, so it's not so clear to me which is the easier drug to get through to approval

lastly, just to dispell the notion that copaxone is a complete black box, note that TEVA uses a variety of analytics (see their latest CP) for QC to ensure batch to batch consistency, so by their own admission there are ways of characterizing copaxone to some degree with analytics