Sunday, December 21, 2014

Merck May Pay $50 Million For NewLink's rVSV ZEBOV Ebola Vaccine Candidate, But May Sell The FDA Voucher For $125 Million

Early on, with a torrent of good data (some of it in blue below), our "Birdman" cogently pointed out that there were many a soft dollar incentive already embedded in the global race to develop an Ebola vaccine. The list of those incentives has lengthened appreciably here in December. There will be $300 million in GAVI vaccine purchasing money, and there is now nearly bullet proof tort immunity, under the PREP Act from injury suits, for the vaccine makers -- should they win FDA approval.

Now add to this that a freely transferable FDA "Priority Review" Voucher goes to the winner of the Ebola sweepstakes. Very recently, just such a voucher sold for $125 million. While Merck will doubtless have something like $200 million in development and scale up costs here, near term -- recall that Whitehouse Station will only pay a maximum of $50 million to NewLink for all the rights to the rVSV ZEBOV candidate. So, Merck's net investment -- the amount it would need to cover -- via future sales, might be only be $125 million (or $250 M minus $125 M). And it would doubtless win the lion's share of that GAVI $300 million, so it would be. . . in the black, even as the first commercial sales occur. And of course, Merck will likely need to give it away (or nearly give it away), in several geographies in West Africa.

All of that said, I suspect Merck will keep the FDA bonus voucher, near term, and use it for a program of its own. The value in that case mght be well north of $200 million -- if it gave a six month lead in the market to Merck, on some other hotly contested field. Here's some backrgound, on the relative benefits of durability in the vaccine, from Bridman, followed by an earlier bit from Modern Medicine's Formulary Watch:

Birdman 11.30.14 --

. . . .I do not believe that durability of the immune response is a critical issue during the outbreak and for curtailing the outbreak. The durability must be moderate...perhaps 6-10 months. Ten months was achieved with the ChAd3-EBOL vaccine which was boosted with MVA-EBOL. Durability IS an issue in populations which are exposed to endemic ebola virus after the outbreak has been stopped. To stop the outbreak one needs a single dose vaccine that generates fast, high level immune responses against ebola. The vaccine would also optimally NOT generate signs or symptoms commonly associated with EVD. This could lead to vaccinees and contacts thinking they have ebola.

Stanley clearly showed poor durability of ChAd3-EBOL as a stand alone vaccine in NHP and that heterologous boosting with MVA vectored GP was needed to achieve 10 months of protective immunity. Also shown was that MVA vectored GP was a very poor standalone vaccine.

Stanley, D.A., et al., 2014. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nat. Med. 20, 1126–1129. doi:10.1038/nm.3702

Unfortunately we only have indirect evidence that the VSV vectored elola Zaire vaccine will elicit durable responses. There are no NHP durability data published for the VSV-Zaire vaccine...only the VSV-Marburg vaccine:

Mire, C.E., et al., 2014. Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates. PLoS ONE 9, e94355. doi:10.1371/journal.pone.0094355

However, As I mentioned in a previous post, I believe the human anti GP ELISA titers elicited with the VSV vector will be higher than those generated with the ChAd3 vector and this alone is likely to lead to a durability better than that generated with ChAd3. . . .

[Formulary Watch:]

. . . .The FDA initiated its PRV program, which allows companies to transfer PRV approvals, in 2008 to encourage development of drugs to prevent and treat tropical diseases that affect millions of people globally. “There has been remarkably little progress over the last 50 years in development of drugs for these diseases. Because these diseases are found primarily in poor and developing countries, existing incentives have been insufficient to encourage new and innovative drug therapies,” FDA wrote in its Guidance for Industry. . . .

Drug manufacturers can apply for applications for PRVS for tuberculosis, malaria, blinding trachoma, Buruli ulcer, cholera, dengue, leprosy, and other diseases, particularly infectious diseases for which there is no signficant market in developed countries and that disproportionately affects poor and marginalized populations, according to FDA. . . . [Ed. Note: Ebola vaccines just added to this list.]

So now we await the first efficacy trial results. I still think we will see the beginnings of those results by early February. And I for one expect Merck's candidate to be the clear leader here. Which means. . . "Birdman" is right -- Merck will almost certainly NOT lose money on this deal. And it will have done well, by doing good. And that's the way it ought to be.

[As a side note, maybe our Birdman is a jazz head -- maybe he references Charlie Parker. We will wait for word, in comments. I can source a good graphic with that Birdman as the avatar, too. Smile. . . .]


Anonymous said...

Any word on TECOS?

Condor said...

Hmmm. . .

I've seen nothing official yet.

But the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (a Merck blockbuster) is ongoing. . .

Will report when something breaks.

Thanks, Namaste -- and do look back in!