Pharma’s Cutting Edge

I am pleased to offer my hearty congratulations to GSK for admitting no wrongdoing in response to allegations that it defrauded the US government of millions of dollars. Oh, and for paying only $150 M for this privilege. That’s quite a return on investment, wouldn’t you say? Oh sure, GSK doesn’t accrue tangible benefits for the payment, but think of all the intangibles. GSK can now proudly advertise during the prime time news hour that they not only deliver tomorrow’s cures but also do not admit to defrauding federal and state governments. Hey now, quite an achievement. Seriously, no one who cares about the future of this industry should defend such alleged practices or out-of-court settlements. Investors in the sector should not be pleased with this settlement eiether, because there are other, more serious suits pending. And there will be bigger, much bigger settlements to be paid if this case is any indication. This case and its conclusion was a dark stain on an already badly tarnished industry image. How many more stains can pharma sustain before it is no longer recognizable?

Regular readers might recall my somewhat bold prediction at the beginning of this year that the first NDA for a “biogeneric” or “follow-on biologic” would be approved in 2005. I presumed that it would be Omnitrope (recombinant human growth hormone, Sandoz), referencing Genotropin, using the 505(b)(2) pathway for approval. Looks I was was wrong, sort of. You see, another recombinant follow-on biologic was approved in August (Fortical, recombinant salmon calcitonin, Unigene), referencing Miacalcin, using this pathway. Interestingly, although I anticipated final action on the Omnitrope NDA by the time that Fortical was approved, it never came. Now we know the specific circumstances surrounding the Omnitrope NDA approval delay.

In the lawsuit (dcdc05cv1810C.pdf) recently filed in the US District Court (Washington) against HHS and FDA, Sandoz has charged that FDA has been delinquent in its duties to offer a final action timely in its review of the Omnitrope NDA (which we learned, vide infra, was filed in October 2003), based on the reasoning that there were “unresolved scientific and legal issues that relate to [the] NDA.” However, Sandoz makes the case–and I think they make it very effectively–that these issues have been effectively resolved and that final action should now be taken on the NDA. FDA, for its part, maintains that they have no timetable for final action. Presumably, they are relying on a loophole of the FDC Act and/or PDUFA to shield themselves from the requirement to take a final action.

This is a very interesting case from every perspective, scientific, legal and political and should be observed closely. The outcome could well decide when the first major recombinant follow-on biologic, and the first human recombinant follow-on biologic hits the US market.

I’m not going to spend much time on this one, since I actually agree with many of the criticisms leveled at open-label extensions (OLEs) of previously blinded clinical trials as discussed in the article. The principles that should be adhered to when conducting open-label extensions are those of the scientific method and good clinical practice (GCP), not good marketing practice. It is that simple. When we ask subjects to participate in such studies, we should do so with full disclosure of the risks, benefits and treatment alternatives available to them, and we should be forthright in explaining to them the advantages and limitations of the open-label extension design. Any inducements beyond supply of drug and study-related medical care to subjects agreeing to participate should be minimal and non-coercive. That said, we should not throw away the baby with the bath water. Just because pharma has shirked its responsibility to publish OLEs does not mean pharma and the research community should abandon the OLE study. OLEs offer certain advantages over blinded trials, including collection of long-term safety, tolerability and adherence data that might otherwise not be possible. They also serve an important marketing role. However, this role must take a back seat to the welfare of clinical trial participants and to the integrity of the clinical trial process.

Part of the problem is one of continuing insufficient interaction between marketing and R&D personnel within industry. Most companies still pay lip service to this interaction. The two functions work with each other more often and earlier in development than ever before, but little attention is paid to understanding each other’s roles in a truly meaningful way. This must change. It is critically important that these functions cooperate in a meaningful way, in which each continuously informs the other of its practices, motivations and rules of conduct. Fix this interaction, and many of the ills plaguing questionable pharma R&D practices go away.