Contravir Pharmaceuticals Inc. has enrolled the first patient in what could be the sole pivotal trial of FV-100, an oral herpes zoster therapy, that it hopes to market as a treatment for both shingles and the reduction of post-herpetic neuralgia (PHN), a painful shingles-associated condition that becomes more common as people age.

Should it succeed, Contravir CEO and President James Sapirstein told BioWorld Today that he believes it could achieve between $750 million and more than $1 billion in sales of the drug, depending on the dosing regimen and how significantly it reduces PNH, which is treated today with various products, including lidocaine and capsaicin patches as well as opioids in some cases.

To measure FV-100's potential, Contravir is comparing the drug to valacyclovir, an FDA-approved shingles drug in a phase III study that will measure reduction in the incidence of PHN as its primary endpoint. The double-blind, parallel-group, comparative trial, called study 007, will randomize patients to one of three arms: FV-100 400 mg once a day, FV-100 400 mg twice a day or valacyclovir 1,000 mg three times a day. Patients will then be analyzed for a seven-day treatment period, tracking their PNH pain daily, with follow-up through day 120.

Depending on how difficult it is to enroll the 825 patients needed for the trial, FDA reviewers have left open the possibility that they may require just one pivotal trial before allowing Contravir to submit its new drug application for FV-100. Determining how likely that possibility is will take time and a few meetings with agency staff, Sapirstein said.

The biggest study of FV-100 to date, a phase II trial started in May 2009, was encouraging, but failed to show a statistically significant advantage for the drug over valacyclovir in reducing the incidence of PNH. The double-blind, randomized trial, called study 005, was run by Inhibitex and included 350 patients who received either 200 mg or 400 mg of FV-100 once daily or 1,000 mg valacyclovir three times daily. Only 12 percent of patients treated with the 400 mg dose of FV-100 developed PHN vs. 20 percent of valacyclovir-treated patients, according to Thomson Reuters Cortellis Clinical Trials Intelligence. Despite pointing to FV-100's potential, the study was hobbled by sporadic collection of pain data, "so while the results were very positive, they just missed the endpoint," said Sapirstein. Given improvements in the standard measurements of pain since, he said Contravir will be able to deliver a better result, potentially approaching a 50 percent reduction in the incidence of PNH or better (See BioWorld Today, Oct. 26, 2009.)

Edison, N.J.-based Contravir is a spinout of Synergy Pharmaceuticals Inc., which acquired FV-100, from Bristol-Myers Squibb Co. for $1 million in August 2012. BMS had acquired the drug via the $2.5 billion Inhibitex Inc. buyout earlier that year. Prior to that, the drug was first developed by Fermavir Pharmaceuticals Inc., which identified the nucleoside analog as a prodrug of CF-1743, a compound that the Welsh School of Pharmacy had identified as a potential treatment for varicella zoster virus and HIV. (See BioWorld Today, April 11, 2007.)

Chris McGuigan, a professor of medicinal chemistry at Cardiff University in Wales and the discoverer of FV-100, joined Synergy's board in 2008 and continues there today. When Synergy, which chiefly focuses on gastrointestinal diseases, decided to spin out Contravir in February 2014, he joined Contravir's board as well. (See BioWorld Today, Nov. 30, 2011.)

To carry the drug forward, Contravir raised $9 million through the private placement of series A convertible preferred stock to a non-U.S. investor, a deal it completed in October 2014. That financing also included a side note for an additional $3.5 million that the investor exercised through the first and second quarters of this year. Despite the $12.5 million raised, Contravir will need to raise additional funds to complete the current phase III study, which could take about two years to complete, said Sapirstein. (See BioWorld Today, Jan. 10, 2012.)

Contravir also is developing CMX157, an analog of Gilead Sciences Inc.'s tenofovir DF (Viread), for the hepatitis B virus, a program it hopes to advance into phase II by the end of the year. Licensed from Chimerix Inc. in exchange for an up-front payment of 120,000 preferred shares of Contravir valued at $1.2 million, CMX157 is active against HBV and appears from early studies to be more than four times more potent in vitro versus tenofovir, according to the company. Chimerix is eligible to receive up to about $20 million in clinical, regulatory and initial commercial milestones in the U.S. and Europe, as well as royalties and additional milestones based on commercial sales in those territories under deal terms.

Contravir shares (NASDAQ:CTRV) rose 6.5 percent, or 31 cents, to $5.11 on Monday.