After a decidedly lukewarm response from the FDA advisory panel yesterday on Novo's GLP-1 analog hopeful liraglutide (Victoza), your IN VIVO Blog team wonders whether Novo actually wants the drug to get out there after all.Okay, so we were drawn in by the Danish group's absolute confidence prior to the meeting that the drug wouldn't stumble at FDA's cardiovascular hurdles, part of new diabetes guidance that was released after liraglutide was submitted. That confidence stuck even after it was revealed that Takeda's alogliptin--also submitted pre-guidance--would need to meet the higher safety standards.
And Novo was right, it seems, about the CV issue: it wasn't an issue. A majority of the panel voted that there was appropriate evidence of CV safety. In the event, thyroid c-cell tumors seen pre-clinical studies in rats and mice provided the...er, fly in the soup. Only one panelist agreed with Novo that this data was not relevant to humans. (See our Pink Sheet DAILY coverage yesterday.)
On a conference call early this morning to discuss the committee's findings (download a replay here), Novo's CMO Mads Krogsgaard Thomsen declared he was "still convinced that this [effect] is rodent specific." He was also relatively quick to draw in other GLP-1s, though; "this is a class effect. Once-weekly compounds including our own tend to produce c-cell changes in mice and rats, but in my mind not in monkeys or humans based on the data we have today." (Liraglutide is once-daily, but Novo has a once-weekly compound in Phase II.)
So in other words, if we go down, Byetta LAR (which Lilly plans to file at the end of 2Q this year) will go down with us (although LAR's rat studies showed more c-cell carcinomas only at the very highest dose, so it may get away with it). But even if LAR is impacted too, that still leaves Lilly/Amylin with a nice monopoly around the current, twice-daily Byetta--and, as Catherine Arnold of Credit Suisse points out, if LAR and liraglutide are required to conduct similar studies on thyroid cancer risk, LAR wins since the drugs' filings will then be very close together, with GLP-1 virgin Novo Nordisk at a disadvantage.
But--and here's the point, patient blog-readers--maybe Novo secretly (or less secretly) just hopes that liraglutide (and other long-acting GLP-1s) will just go away. Thomsen re-phrased an analyst question about the impact of GLP-1s on the insulin market. "What would happen if the GLP-1 class disappeared? This would not necessarily be a totally negative scenario for Novo Nordisk," he said.
No indeed. Novo's a leader in insulin, and 70-80% of its expected growth in the next ten years comes from modern insulin. Those figures came straight from the company's mouth on this conference call too. So did "If there are no GLPs, you might argue that [our growth] will be even stronger."
"But this is totally hypothetical," Thomsen clarified immediately after, as if coming back down to Earth from some insulin-infused dream. "We're trying to get liraglutide approved, because it offers a significant advance for diabetes patients."
Analysts' first take is that liraglutide is unlikely to get past FDA in 2009, although Leerink Swann adds that a "final rejection also appears unlikely." In between lie the possibilities of a black box warning, higher monitoring requirements and further studies--including pre-approval. None will do liraglutide much good. So we may not be totally off-base in suggesting that Novo wishes it has just stuck with insulin.
image--dreaming--from flikr user h.koppdelaney used under a creative commons license
Novo's confidence is admirable, but may be a bit foolish, both when it comes to Victoza and "modern insulins". The reason: Novolog/Novorapid's U.S. patent expires in 2013, a mere 4 years away, and by then, it is almost certain that follow-on versions will have an approval pathway outlined by Congress (technically, insulin is grandfathered under the Federal Food Drug and Cosmetics Act, and therefore could be subject to follow-ons today, although the FDA has been dragging its feet on issuing guidance), but an ambitious generics maker might push the issue using the 505(b)(2) pathway and the FDA might have to consider such an application, just as it did with Omnitrope HGH. Novo's other "modern" insulin has a few more years before subject to follow-ons, but that product, as a "me-too" to Sanofi's Lantus, isn't quite the blockbuster Novo hoped it would be, at least according to IMS sales data. Novo may be playing it cool, but we can be sure management is nervous as hell right now.
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