The price for a priority review voucher (PRV) jumped another level with United Therapeutics Corp.'s sale of its FDA accelerator to a subsidiary of Abbvie Inc. for more cash than any firm has paid for the certificate so far: $350 million. "I'm surprised they're going for this much," attorney Kurt Karst with Hyman, Phelps & McNamara told BioWorld Today. "But time is money. If you're reasonably certain you're going to get the approval, four months [quicker review time vs. the usual 10] on a multi-billion dollar per year drug could be a lot."

Four PRVs have been sold, and for a higher amount each time. "Are they going to continue to go up? If you plot these out, yes," Karst said. "And they're not going up by little increments, either."

In May, San Diego-based Retrophin Inc. disclosed the sale of its PRV to Sanofi SA, of Paris, for $245 million ($150 million up front and two $47.5 million payments in 2016 and 2017). Retrophin brought aboard the voucher from Baltimore-based Asklepion Pharmaceuticals LLC as a result of U.S. marketing clearance in March for Cholbam (cholic acid). The drug is prescribed for adults and children with bile acid synthesis disorders due to single enzyme defects, and for those with peroxisomal disorders, including those in the Zellweger spectrum. Last year, Foster City, Calif.-based Gilead Sciences Inc. paid $125 million to Knight Therapeutics Inc., of Montreal, for a PRV. San Rafael, Calif.-based Biomarin Pharmaceutical Inc. sold its PRV to Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., for $67.5 million. (See BioWorld Today, Aug. 1, 2014, and March 19, 2015.)

In 2007, when PRVs came into being, "some economists said they would [sell] for $500 million, and several folks scoffed at that," Karst said. "But there will be a plateau. There's got to be, at some point."

J.P. Morgan analyst Jessica Fye called the PRV sale a "clear positive" for United, which could use the money for continued stock repurchasing. Management has "suggested they will continue to buy stock up to the $200-per-share range," analyst Fye wrote in a research report, though "the board would likely need to authorize another program, as the current one was expected to be completed in July."

Shares of United (NASDAQ:UTHR) closed Wednesday at $167.68, up 10 cents. Silver Springs, Md.-based United could not be reached, but Chief Financial Officer James Edgemond noted during the second-quarter earnings call last month that "we've done the accelerated share repurchase and we've also done it through the open market," as the company stays "committed to share repurchases."

United reaped its PRV by way of the approval in March of Unituxin (dinutuximab) for the rare pediatric disease neuroblastoma. PRVs can be used to gain priority review for products otherwise not eligible, thanks to an incentive first intended to spur research against tropical conditions. Rare pediatric diseases were added later. (See BioWorld Today, Oct. 3, 2011, and March 11, 2015.)

"Bigger picture, we see the launch of Orenitram [treprostinil extended-release tablet for pulmonary arterial hypertension (PAH)] as the key near-term driver of United's shares," Fye wrote. "Recall that the company posted sales of $21 million and $26 million for the product in the first and second quarters, respectively, with comments on the most recent call indicating it could clear $30 million in the third quarter." Said another way, in the second quarter of this year, Orenitram sales grew nearly 300 percent as compared to the second quarter of 2014, when the product hit the market. The drug won the FDA's nod in late 2013 after garnering two complete response letters. Previously, treprostinil was available only in injectable (Remodulin) and inhalable (Tyvaso) forms. (See BioWorld Today, Dec. 24, 2013.)

Also on Wednesday, Liestal, Switzerland-based Santhera Pharmaceuticals Inc. said the FDA granted rare pediatric disease designation for its lead fast-tracked orphan drug candidate, idebenone, to treat Duchenne muscular dystrophy, which could mean a PRV for the company if the drug wins approval. Santhera's stock (SWX:SANN) closed Wednesday at $95.95, up $4.95.

TROPICALS MORE TOPICAL

Another firm that could snag a PRV is Paxvax Inc., of Menlo Park, Calif., with PXVX0200, which could become the first cholera vaccine approved for marketing in the U.S. At the end of last year, Paxvax disclosed positive phase III results from a safety and lot-to-lot consistency trial of the single-dose oral candidate, which uses the same attenuated vaccine strain (CVD 103-HgR) approved and marketed in several countries under the brand name Orochol. Paxvax said it intended to submit a biologics license application (BLA) for the product, to be branded Vaxchora, to the FDA around the middle of this year. (See BioWorld Today, Sept. 9, 2013.)

Owning a PRV not only means a four-month review time difference but also potentially for the first-to-market advantage, as with the race between Regeneron/Sanofi and Thousand Oaks, Calif.-based Amgen Inc. with their competing proprotein convertase subtilisin/kexin type 9 inhibitors for high cholesterol. Last month, the European Union approved Amgen's Repatha (evolocumab), but Regeneron/Sanofi's Praluent (alirocumab) led the race in the U.S., chalking up clearance from the FDA less than a week later. (See BioWorld Today, July 22, 2015, and July 27, 2015.)

Of the six PRVs earned thus far, one was used for the priority review process by the original sponsor, Basel, Switzerland-based Novartis AG, four were sold, and one has not been sold or used: the PRV for the 2013 approval Sirturo (bedaquiline) for multidrug-resistant pulmonary tuberculosis from Johnson & Johnson, of New Brunswick, N.J. (See BioWorld Today, Jan. 3, 2013.)

Karst's law firm in Washington has been involved in negotiations regarding PRVs. "I can't say which ones, but we're familiar with them," he said. Owning a voucher hardly guarantees approval and may even skew the odds in the wrong direction, he added. "Who knows? What if you get a complete response because the FDA had to rush through with the priority review? Now you've bought yourself a longer approval," he said. In 2009, Novartis was awarded the first-ever PRV in conjunction with the FDA's approval of Coartem (artemether/lumefantrine) for multidrug-resistant malaria. The pharma firm used its voucher to speed the review of its supplementary BLA for Ilaris (canakinumab) in gouty arthritis. Though cleared for marketing in 45 countries, including the U.S., for cryopyrin-associated periodic syndrome (CAPS) in children and adults, Ilaris 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.)

U.S. regulators recently added two tropical conditions to the list of those eligible for PRVs: Chagas disease and neurocysticercosis. The first, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi, found mainly in endemic areas of 21 Latin American countries. It's transmitted to humans by contact with feces of triatomine bugs, known as "kissing bugs." The World Health Organization (WHO) estimates as many as 7 million people may be infected. Neurocysticercosis is a preventable parasitic infection of the central nervous system and is caused by the pork tapeworm Taenia solium. Humans become infected after consuming undercooked food, particularly pork, or water contaminated with tapeworm eggs, or through poor hygiene practices, WHO said, and the disease is the most frequent preventable cause of epilepsy in the developing world.