Biotech Values

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>>> Gilenia Set to Rock the MS World <<<


Here's a 6-24-10 update on Novartis' MS drug 'Gilenia', from the NI Research / NeuroInvestment website (Dr. Harry Tracy) -

http://www.neuroinvestment.com/NewCommentary.html


>>> Gilenia Set to Rock the MS World

Gilenia is effective in reducing relapse: 25-0
Gilenia delays disability: 24-1
Gilenia should be a first-line therapy: 21-3
Gilenia is safe (enough) for its intended use: 25-0
Gilenia should be tested at a lower dose post-approval: 20-5

The FDA Advisory Committee votes for Novartis' MS drug Gilenia/FTY720/fingolimod were less ambivalent, and portend more for Gilenia's prospects, than NI had anticipated. We had expected that efficacy would be deemed established, but there was somewhat less angst about Gilenia's side effect/AE profile than we had forecast, given the FDA's past experience with Biogen-Idec/Elan's Tysabri. The FDA will undoubtedly still insist on a REMS program that will pinpoint any emerging adverse events earlier rather than later, and baseline cardio, pulmonary, and vision testing will likely be required. But two of the aforementioned recommendations stand out in their probable impact on the MS market.

First, had the AC defined the minimum effective dose as needing to be established before approval, that trial would have delayed approval by years. Novartis has already stated that they will run a major Phase IV, doing so post-approval will allow Gilenia a vital head start as the first oral immunotherapy for MS. This is an area where the bar may be raised considerably for the second oral drug to be considered. The prospects for the other several immunotherapies in late clinical development (e.g. Campath, cladribine, laquinimod, BG-12, daclizumab) could well be colored by Gilenia's advent and performance, because the FDA could tighten up on later entrants IF Gilenia proves relatively safe and predictable. On the other hand, it has enough question marks in terms of longterm safety that the FDA could be receptive to anything that offers the prospect of an improved risk-benefit calculation. MediciNova's ibudilast is much earlier in development, and recent evidence that it acts via MIF (macrophage migration inhibiting factor) leaves open a small possibility that this anti-inflammatory tactic might turn out to have unexpected immune system implications.

For now, with Tysabri generally seen as a second-tier, post-ABC therapeutic step, to have Gilenia endorsed as a first-line therapy option puts it in an entirely different risk category from a regulatory and prescriber point-of view. The fact that it is orally-administered (even if the first dose is supposed to be done at the MD's office) will overcome a significant source of patient resistance.

There is always the possibility that the FDA could err on the side of greater caution in its final response to the NDA, but there is no clinical basis for that, and no discernible regulatory agenda in that direction. While Merck Serono has refiled the NDA for cladribine, we do not expect that cladribine is now going to have an accelerated path forward in the wake of having its initial filing refused by the FDA. Gilenia will be the first-to-market of the oral alternatives. What does this mean for the MS market in the United States?

Novartis can expect rapid user uptake, as patients who have been on-the-fence about Tysabri jump off, and on to Gilenia's bandwagon-to-be. Barring some unexpected AE that arises as use expands, as has now been the case with Tysabri and PML, Gilenia's market potential will be on the high side of the $1 billion to $2.3 billion range we have seen from various analyst estimates.

As the major US player for MS, via both Avonex and Tysabri, no one is more vulnerable to Gilenia than Biogen-Idec. Patients who ordinarily would have embarked on a first course of Avonex may well start with Gilenia instead, those whose response to a beta-interferon or Copaxone is flagging, for whom Tysabri would have been the next step, will look at Gilenia first. The value of a PML predictive test will be been diminished, because, one can entirely avoid PML risk by taking the Gilenia route. Risk-averse prescribers and patients may choose to wait for a larger mass of clinical safety data to be developed for Gilenia, but that end of the user spectrum is the least likely to utilize Tysabri, particularly as the number of PML cases continues its inevitable rise (now at 55). The question to be answered by sometime in 1Q:11 will not be whether Tysbari has regained sales growth momentum, it will be whether one any decline in utilization has yet become apparent.

This was the nightmare scenario for Biogen-Idec, and is hardly better for Genzyme, Teva, or Merck Serono. Barring a surprise from the regulatory or safety side, it will come to pass. <<<