With positive Phase III data in hand, Versicor Inc. reiterated plans to file a new drug application by the end of next month for its lead candidate, anidulafungin.
The pivotal trial hit its primary endpoint, demonstrating the antifungal agent's non-inferiority to fluconazole in treating esophageal candidiasis. In the trial, 97.2 percent of anidulafungin patients (242 out of 249) and 98.8 percent of oral fluconazole patients (252 out of 255) showed endoscopic success at the end of therapy. The latter remains the standard of care for the fungal infection of the esophagus found in patients with poor immune systems.
"Our requirement for approval was non-inferiority, so we met that requirement for our primary endpoint," Dov Goldstein, Versicor's vice president of finance and chief financial officer, told BioWorld Today. "We had a very nice safety profile vs. fluconazole, and a very nice safety profile on a stand-alone basis. We think we have an approvable drug for esophageal candidiasis."
But the market reacted negatively to a missed secondary endpoint. King of Prussia, Pa.-based Versicor's stock (NASDAQ:VERS) fell $1.93 Tuesday, or 14.9 percent, to close at $11.07 after data also showed that patients receiving anidulafungin demonstrated a 35.6 percent relapse rate (83 of 233), compared to 10.5 percent of fluconazole patients (24 of 229), 14 days following treatment.
Versicor stressed that esophageal candidiasis is typically recurrent in an immunosuppressed population, as evidenced by the significant percentage of relapse in both arms.
"It's not a matter of whether they are going to relapse, but it's just a matter of when," Goldstein said. "This becomes a non-issue clinically because you put them on prophylactic therapy with an oral medication to prevent that. We think the clinical relevance of the endpoint is very small."
Thomas Dietz and Gregory Wade, analysts with Pacific Growth Equities Inc. in San Francisco, agreed.
"This observation, in our opinion, is unlikely to impact the marketability for the drug," they wrote in a research note. "This clinical trial does not replicate the current standard of care for esophageal candidiasis, which in clinical practice sees patients receive prophylactic therapy once their disease has been cleared, and while the Phase III study was completed in esophageal candidiasis, the target market for the drug is candidiasis/candidemia and invasive aspergillosis."
Pacific Growth makes a market in Versicor's securities.
Versicor said its FDA submission would include data from the esophageal candidiasis trial, as well as data from a previously reported Phase II study in invasive candidemia/candidiasis. The company also plans to include interim safety data from an ongoing Phase III trial studying anidulafungin in aspergillosis in 17 patients over a 90-day period after receiving a high dose of anidulafungin, a naturally occurring molecule that belongs to the echinocandin class of antifungal agents. The first new class introduced in more than 40 years, echinocandins have been shown to avoid resistance problems associated with the azole class of drugs, to which fluconazole belongs.
"This market for injectable antifungals is largely made up of invasive candidemia/candidiasis - more than 80 percent of the market for this drug," Goldstein said, adding that both the lead esophageal candidiasis indication and the aspergillosis indication are much smaller pieces of the pie. "The real question Versicor faces is whether this is an approvable drug, and we feel that we have met the hurdle of being efficacious, and it is safe. We think it is a therapy for esophageal candidiasis, and once we get it approved we think we will get off-label use in the main market - invasive candidiasis."
The esophageal candidiasis trial compared intravenous anidulafungin vs. oral fluconazole in about 600 esophageal candidiasis patients in the U.S., South Africa, Thailand and Argentina.
Patients in the anidulafungin arm were treated with a 100 mg intravenous loading dose of anidulafungin on the first day along with an oral placebo, followed by daily 50 mg anidulafungin infusions plus oral placebo for 14 to 21 days. Patients in the fluconazole arm were treated with a 200 mg dose of oral fluconazole on the first day along with an intravenous placebo, followed by daily 100 mg oral fluconazole doses and an infusion of placebo for 14 to 21 days.
Data showed the study met its statistical requirement for non-inferiority at the end of the trial. Safety data demonstrated anidulafungin to be as well tolerated as fluconazole, with an adverse event and laboratory safety profile comparable to oral fluconazole.
"The current standard of care is IV fluconazole, a drug that just inhibits but does not kill the fungi," Goldstein said. "Our drug kills the fungi."
He added that anidulafungin provides a broader spectrum, showing activity against the non-Candida albicans species of candida, a major cause of fungal infections that tends to resist fluconazole. Goldstein also said anidulafungin is safer than amphotericin, which can be toxic to the liver and negatively affects kidney function, and Cancidas, which reacts negatively with cyclosporine, an immunosuppressant drug used in organ and bone marrow transplant patients.
Beyond anidulafungin, Versicor features another Phase III product, dalbavancin. Dosed once a week as an intravenous antibiotic for Gram-positive infections, two studies will conclude during the first half of next year with results to follow shortly after, Goldstein said. Another Phase III product, ramoplanin, is being developed to prevent enterococcus infections in partnership with Waltham, Mass.-based Genome Therapeutics Inc. Phase I data is expected to be released during the second quarter for another clinical candidate, BI-K0376, a topical acne antibiotic.
Earlier-stage programs expected to enter the clinic this year are being developed in partnership with Peapack, N.J.-based Pharmacia Corp. and Basel, Switzerland-based Novartis AG.