Might as well post the trial results for comparisons . . .
>>KING OF PRUSSIA, Penn., March 17 /PRNewswire-FirstCall/ -- Versicor Inc. (Nasdaq: VERS; Nuovo Mercato: VER) today announced positive results from a pivotal Phase III clinical trial with the company's lead investigational product candidate, anidulafungin, an anti-fungal agent, and reiterated its intention to file a New Drug Application for anidulafungin with the United States Food and Drug Administration (FDA) by the end of April of this year.
The trial showed that anidulafungin is as effective as fluconazole, the standard-of-care for the treatment of esophageal candidiasis, a painful and debilitating fungal infection of the esophagus that commonly affects patients with compromised immune systems. Anidulafungin belongs to the first new class of anti-fungal agents, called echinocandins, introduced in more than 40 years.
"That the primary endpoint in this study was fulfilled marks an important benchmark for the development of anidulafungin," said Dr. Thomas J. Walsh, co- author on the study and Senior Investigator at the National Cancer Institute and Chief of the Immunocompromised Host Section. "This large clinical trial demonstrates proof of principle that this echinocandin is comparable to fluconazole in treatment of esophageal candidiasis in humans." Dr. Walsh further observed, "The data are consistent with our preclinical studies demonstrating the safety and efficacy of anidulafungin in experimental esophageal candidiasis. The new class of echinocandins offers broad-spectrum alternatives in the treatment of invasive fungal infections that include candidiasis and aspergillosis. Compounds within this class have low potential for emergence of resistance, an excellent safety profile, and minimal drug- drug interactions. Anidulafungin promises to be an important addition to our current antifungal armamentarium for treatment of invasive fungal infections in seriously ill patients."
"This data, along with positive data from the previous trials, will form the basis of what we believe will be a strong NDA submission to the FDA," said Timothy J. Henkel, M.D., Ph.D., Versicor's chief medical officer.
The NDA submission will include data from the Phase III esophageal candidiasis trial; data from a previously reported Phase II study in invasive candidemia/candidiasis, the most common hospital-based fungal infection with high mortality rates; and interim safety data from an ongoing Phase III trial studying anidulafungin in aspergillosis, another serious, opportunistic fungal infection with high mortality rates.
Phase III Esophagael Candidiasis Clinical Trial Results Summary
This randomized, double-blind, double-dummy Phase III clinical trial studied the safety and efficacy of intravenous anidulafungin versus oral fluconazole in the treatment of approximately 600 patients with a documented diagnosis of esophageal candidiasis in the United States, South Africa, Thailand and Argentina.
Patients in the anidulafungin arm were treated with a 100 mg intravenous loading dose of anidulafungin on day one 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 day one along with an intravenous placebo, followed by daily 100 mg oral fluconazole doses and an infusion of placebo for 14 to 21 days. Treatment ended when the patient remained symptom-free for seven days, with a maximum of 21 days on therapy.
Patients were examined for endoscopic, clinical and mycological responses at the conclusion of therapy and two weeks following therapy. The primary efficacy endpoint was endoscopic success at the end of therapy (EOT) in clinically evaluable patients, which was 97.2 percent (242/249 patients) with anidulafungin and 98.8 percent (252/255) with oral fluconazole. The statistical requirement for non-inferiority was easily met, as the lower bound of the 95 percent confidence interval ("the delta") was minus 4.1 percent, well within the prospectively specified minus 10 percent limit. In addition, anidulafungin was well-tolerated, with an adverse event and laboratory safety profile comparable to oral fluconazole.
Esophageal candidiasis in an immunosuppressed population is typically recurrent and, as expected, a significant percentage of patients in both arms relapsed, with the anidulafungin arm demonstrating a higher relapse rate than the fluconazole arm. Endoscopic success at the two-week follow up in clinically evaluable patients was observed in 64.4 percent (150/233) of patients in the anidulafungin arm and 89.5 percent (205/229) of patients in the fluconazole arm, which was a statistically significant difference.
"Both treatments proved highly effective at the end of therapy based on endoscopic response, the most objective measure, as well as clinical and mycological responses, which were secondary endpoints," added Dr. Henkel. "End-of-therapy response, rather than follow-up, is most significant in this disease because almost all patients eventually relapse. As expected in this trial population, relapse rates in both groups were substantial. However, this has little clinical relevance because current clinical guidelines and standard practice call for follow-up prophylactic therapy."
In terms of safety, anidulafungin was as well tolerated as fluconazole. The most common treatment-related adverse events included phlebitis, nausea and thrombocytopenia. There were no systemic infusion reactions and no evidence of hepatic toxicity.
Invasive Candidiasis/Candidemia Phase II Results
Results from a 120-patient randomized, open-label Phase II clinical trial demonstrated at the end of therapy an 89 percent global response rate in patients with a documented diagnosis of invasive candidiasis/candidemia receiving a 200 mg intravenous loading dose of anidulafungin followed by a 100 mg maintenance dose per day. The response rate was 90 percent with an analogous anidulafungin regimen of 150 mg followed by 75 mg per day, and 84 percent with 100 mg followed by 50 mg.
Outcomes in evaluable patients at the two-week, test-of-cure visit demonstrated an 83 percent global response rate with a loading dose of 200 mg followed by a 100 mg maintenance dose per day. The response rate was 85 percent with an analogous anidulafungin regimen of 150 mg followed by 75 mg per day, and 72 percent with 100 mg followed by 50 mg.
Global response rates reported in previous clinical trials with other agents, such as fluconazole, amphotericin B and caspofungin, range from 56 percent to 81 percent in patients with invasive candidiasis/candidemia. Anidulafungin is now being studied in an ongoing Phase III clinical trial for invasive candidiasis/candidemia.
About Anidulafungin
Anidulafungin is a naturally occurring molecule that has been significantly improved through chemical modification. In vitro studies have demonstrated that anidulafungin combines both the potency and killing effects of the polyene class (e.g., amphotericin B) without the resistance problems found with the azole class (e.g., fluconazole). Anidulafungin is a broad- spectrum agent, and has been demonstrated to be highly potent in vitro against the fungi responsible for serious systemic infections. Preclinical studies have shown that five-minute exposure to anidulafungin in vitro kills more than 99 percent of Candida, including fluconazole-resistant strains. Anidulafungin has no cross-resistance with azoles or amphotericin, and in the laboratory it has proven very difficult to develop resistance to anidulafungin. Anidulafungin also was well tolerated in the Phase I study when given in combination with cyclosporine, the leading chronic immunosuppressive drug.
Conference Call Details
Versicor will host a conference call today at 4:45 P.M. EST to discuss the Phase III clinical trial data. To access the live call or the seven-day archive via the Internet, log on to www.versicor.com. Please connect to Versicor's website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be needed to view the webcast. Alternatively, please call 1-877-252-5863 (U.S.) or 1-706-634-7491 (international) to listen to the call. Telephone replay is available approximately two hours after the call through March 24, 2003. To access the replay, please call 1-800-642-1687 (U.S.) or 1-706-645-9291 (international). The conference ID number is 9084580.<<
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Cheers, Tuck |
