In the race with Amgen Inc. to market a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor for high cholesterol, Regeneron Pharmaceuticals Inc. played catch-up by buying a priority review voucher (PRV) for $67.5 million from Biomarin Pharmaceutical Inc., splitting the cost with alirocumab partner Sanofi SA.

"I think we're the first to buy one," said Michael Aberman, Regeneron's vice president of strategy and investor relations. "We're happy to be part of the ecosystem that helps bring medicines to patients for rare and difficult-to-treat diseases, whether it's rare pediatric diseases or rare tropical diseases. In our view, it's a win all around."

Thousand Oaks, Calif.-based Amgen is expected to ask for U.S. approval of anti-PCSK9 evolocumab in the third quarter, with a launch expected in 2015. Leerink Partners analyst Seamus Fernandez said in a research note that the move "should put Sanofi's launch timeline in line with Amgen's evolocumab launch." Aberman said such "appears to be the case. Time will tell."

New York-based Pfizer Inc. also has a drug in the class: bococizumab, which this spring yielded positive phase IIb data. But the Regeneron/Sanofi and Amgen candidates are the front runners.

Biomarin, of Novato, Calif., was granted the PRV by the FDA in February when it granted approval for the mucopolysaccharidosis type IVA therapy Vimizim (elosulfase alfa). Under the rules, PRVs can be sold at the discretion of the holder. Tarrytown, N.Y.-based Regeneron and Sanofi, of Paris, made known the PRV buy on the same day that the pair unveiled strong data from nine phase III trials with their anti-PCSK9 candidate alirocumab. (See BioWorld Today, Nov. 20, 2013, Feb. 18, 2014, and July 31, 2014.)

The PRV strategy is scarcely taken because PRVs themselves, given to companies as a reward for developing rare-disease drugs, are uncommon. As of last year, only three companies had qualified, in the FDA's view: Redwood City, Calif.-based Paxvax Inc., Novartis AG, and Johnson & Johnson, of New Brunswick, N.J. Paxvax gets its voucher with the approval of its biologics license application for the cholera vaccine candidate, PXVX0200, now in a late phase III study. FDA clearance could come in the fourth quarter of next year.

In March of this year, Knight Therapeutics Inc. – a spin-off from Montreal-based Paladin Labs Inc. – earned a PRV via the approval of Impavido (miltefosine) to treat three forms of leishmaniasis, a disease transmitted by the bite of the female phlebotomine sandfly. Knight, of Montreal, came into being when Malvern, Pa.-based Endo Health Solutions Inc. took over Paladin, and rights to Impavido went to Knight. (See BioWorld Today, Sept. 9, 2013, and Nov. 6, 2013.)

Knight has "been pretty public about [its] desire to sell" its PRV, Aberman told BioWorld Today. The deal with Biomarin has brought renewed interest the prospects of winning the coupon and then using or selling it, Aberman said. "In general, if you're a company that focuses on ultra-rare diseases – and there's a bunch of companies like that now – the value might be in trading [your PRV], because you think you're going to get priority review anyway."

A company with a PRV, awarded at the time of its drug's approval, may use the coupon later to gain priority review for a product not otherwise eligible. That is what Basel, Switzerland-based Novartis did, attaching the PRV when it sought the quicker nod for the supplementary biologics license application related to Ilaris (canakinumab) in gouty arthritis. But Ilaris, cleared for marketing in 45 countries, including the U.S., for cryopyrin-associated periodic syndrome (CAPS) in children and adults, got an advisory panel's thumbs-down in the new indication because of safety concerns already evident in the CAPS label. (See BioWorld Today, June 22, 2011.)

With a bought PRV, then, a company is simply paying the holder for the promise of quicker FDA review, rather than deserving faster consideration because of the nature of the drug. It's a notion that doesn't sit well with everybody. "The company that gets the voucher earns it from the FDA, but what they earn is the ability to sell it," Aberman said. "Yes, [Regeneron] purchased it, but that's the whole idea. Let's put it in perspective. You're talking about getting four months' expedited review [six months vs. the standard 10 months]. It doesn't guarantee approval."

Aberman said the play of free-market forces can only be good for patients. "In this particular case, it's exactly what the intention was, and here's an example of success," he said. "Now, there might be a whole bunch of companies that might be able to raise money from investors who say, 'Gosh, these guys are going after rare pediatric diseases. If they get approved, not only do they get a potential drug – and it may be a small market – but they also get this valuable asset [in a PRV].' That's how it could stimulate development for these rare diseases."

Regeneron's shares (NASDAQ:REGN) closed Thursday at $316.22, down $5.96. Helped slightly by favorable second quarter earnings along with the PRV news, Biomarin's stock (NASDAQ:BMRN) ended at $61.82, up 73 cents. The firm reported $191.7 million in revenues vs. consensus of $159 million. Vimizim revenue "blew away our estimate of $8 million and consensus of $9 million," said Leerink Partners analyst Joseph Schwartz in a research note. "With seven new product candidates in active clinical development, Biomarin has a leading orphan drug pipeline, and 2015 is expected to be an active year for news flow."