Pharma’s Cutting Edge

What your medicine chest would look like in a world where Public Citizen always had its way:

P&G Pharmaceuticals is eliminating its in-house Discovery program. It wan’t a very large program, but the move represents a major change in strategy for the company, which will now rely solely on licensing and acquisitions to fuel its growth in pharmaceuticals. In a related story, J&J had recently announced its intention to shutter its Raritan Discovery labs, shifting some of those jobs to its Springhouse (PA) operations. Unlike P&G, however, J&JPRD will maintain a relatively large Discovery effort. By making this move, P&G is signaling that it intends to become a larger player in the pharma licensing world. Recent trends have indicated that competition for drug licenses at all phases of development has never been greater, with resultant increases in deal valuations. If you’re a small firm with innovative products or you’re an investor, it’s a buyer’s market. My advice…take your time and choose your partners carefully. Up-front cash is important, of course, but it’s not a measure of a great partner or the likelihood of eventual success in the market. For buyers the advice is similar; be more to your partner than just a deep pocket.

And yet another surprise on the metabolic therapeutics front this week. Acomplia (rimonabant) was issued an approvable letter from the FDA yesterday, rather than an outright approval, for rimonabant, the pioneer in the CB1 antagonist (inverse agonist) class for obesity. They received a non-approvable for smoking cessation. Many observers believed that Sanofi-Aventis would gain approval for obesity on the first go-around, myself included, although at least one Wall Street analyst, Tim Anderson of Prudential, was cautious in his optimism, giving a first-round approval probability of under 50%. It’s a major setback for the company, which will now face an unknown delay in the first launch of Acomplia, as they prepare to answer FDA’s objections to approval.

So, what were the issues that gave FDA pause? The company isn’t saying. Here are some possibilities: (1) Manufacturing quality: FDA has used this issue to delay approval of a number of major’s recent products recently, but S-A hasn’t had any recent manufacturing problems made public. (2) Preclinical safety/tox: I highly doubt this is an issue. Much of the preclinical data on rimonabant has been published and looks okay. (3) Clinical safety: Might be playing a role; some issues with depression arose in the clinical trials. But the obesity safety database was large and long enough, and S-A did a reasonably good job investigating the psych issues already. (4) Clinical efficacy: The drug works to aid weight loss. It’s not great, but it’s as good as the other stuff that’s already being sold. That said, there were a large number of dropouts in the Phase 3 obesity program, and that might have given FDA pause, depending on what secondary efficacy analyses showed. But I don’t think so. (5) Label impasse: This has my vote for likeliest reason for a delayed approval. I’m betting that S-A initially tried for a kakameyme indication that included the “metabolic syndrome,” an embattled classification for the grouping of common cardiovascular risk factors thought to be causally related to insulin resistance. My opinion comes from statements S-A’s Doug Greene, clinical leader of the Acomplia program, and other S-A executives have made previously. You see, S-A wants obesity-related complications in its label to get the support from third-party payers it needs to make Acomplia a blockbuster. They might have determined that it wasn’t worth launching the drug with only the uncomplicated obesity claim without having at least one complication claimed–the more complications claimed the better, and the metabolic syndrome best of all. If FDA believes that data supporting a lipid or diabetes complication claim are lacking (I don’t know why they would), S-A might elect to perform an additional clinical trial before re-submitting an NDA. This could mean a delay in US approval of up to two years. If, on the other hand, if this approvable action is the result of S-A deciding that they wanted it all or nothing at all in their label, then they rightly deserve to be severely punished by investors.

Regular readers will note my proclivity for diabetes-related stories. Endocrinology was my first scientific “love” and will always be dear to my heart, so bear with me. This is an interesting story, because it shows how competitive intelligence can essentially fail even under intense scrutiny. To my knowledge, the industry generally believed Novartis to be leading Merck by a good six months in its development of a DPP-IV inhibitor, the first of a new class of orally administered drugs aimed at increasing endogenous GLP-1 by inhibiting its metabolism. Surprise!! How did Merck keep their progress with their DPP-IV inhibitor so quiet? What did they do to pull ahead of Novartis in the latter stages of development? I’m dying to know. Clues to the latter will no doubt come from the NDA packages we’ll see in due course. As to the quietness of their efforts, it has to be more than just keeping the science under wraps. I’ll try to find out some details and will let you know.

Kudos to Pfizer and Affymetrix for being the first to support NIH’s GAIN initiative to sample a large number of genomes for SNPs and not with a trivial investment, either.