BioNumerik Pharmaceuticals commences patient treatment in Tavocept Phase III trial

BioNumerik Pharmaceuticals, Inc. ("BioNumerik") today announced the treatment of the first patients in a global multi-center Phase III clinical trial of Tavocept (BNP7787) in patients with primary adenocarcinoma of the lung, the most common type of lung cancer. In previous studies, Tavocept demonstrated the potential to substantially increase overall and one year patient survival while concurrently preventing and reducing the incidence and severity of common chemotherapy side-effects as compared to other currently available treatments for advanced lung cancer. Tavocept, originated and developed by BioNumerik, is an investigational new drug with potential for oncology and non-oncology indications.

"In two independent studies of first-line use of Tavocept with chemotherapy, we observed an increase in overall survival of up to 6.7 months in patients with primary adenocarcinoma of the lung, the most common type of lung cancer worldwide," said Frederick H. Hausheer, M.D., F.A.C.P., founder, chairman & chief executive officer of BioNumerik.  "If the results of the current Phase III trial prove to be consistent with prior results, Tavocept treatment could result in the largest historically observed increase in patient survival for a first-line agent for the treatment of primary adenocarcinoma of the lung."

The Phase III Tavocept trial is an international, randomized, multicenter, double-blind, placebo-controlled trial to be conducted at approximately 80 to 100 clinical sites in the United States, Russia, Ukraine, Eastern Europe and Latin America. The primary objective is to confirm whether Tavocept plus taxane and cisplatin chemotherapy significantly increases overall survival in patients with advanced primary adenocarcinoma of the lung compared to taxane and cisplatin treatment alone. Tavocept's ability to prevent or mitigate common chemotherapy-induced toxicities will be prospectively evaluated by pre-specified secondary endpoint analyses. BioNumerik estimates that patient enrollment for the trial could be completed in late 2010 to early 2011.

Two smaller randomized, multicenter trials of Tavocept, in combination with taxane and cisplatin chemotherapy, previously demonstrated large increases in overall survival and one year survival, compared to the control regimens, in patients with newly diagnosed (inoperable) stage IIIB/IV primary adenocarcinoma of the lung. These increases include a 6.7 month increase in overall survival (8.9 months in control vs. 15.6 months in Tavocept treated patients), with 60% of Tavocept treated patients vs. 36% of control treated patients alive at one year after randomization in a U.S. Phase II clinical trial, and a 4.6 month increase in overall survival (15 months in placebo vs. 19.6 months in Tavocept treated patients), with 73% of Tavocept treated patients vs. 54% of placebo treated patients alive at one year after randomization in a Japanese Phase III trial. These improved survival outcomes were accompanied by medically and statistically significant reductions in favor of Tavocept treatment in the incidence and severity of side effects commonly observed with the chemotherapy control regimens, including reductions in kidney toxicity, anemia, nausea and vomiting, and treatment discontinuation due to chemotherapy-induced neuropathy.

Meta-analysis supports survival improvements in patients with advanced non-small cell lung cancer (NSCLC):

The results of a comprehensive meta-analysis of these two previous randomized Tavocept trials were published this week by the European Journal of Clinical & Medical Oncology (EJCMO). [link to abstract] The meta-analysis examined survival outcomes for a combined total of 346 newly diagnosed randomized patients with advanced NSCLC participating in the two trials, including 211 randomized patients with primary adenocarcinoma of the lung. All patients received treatment with taxane plus cisplatin chemotherapy. Approximately half of the patients were treated with Tavocept while the other half received chemotherapy alone. The analysis demonstrated a significant overall survival benefit in favor of Tavocept treatment for the combined meta-analysis of the two trials. For the adenocarcinoma subtype, the combined analysis demonstrated a significantly>

"The results of the meta-analysis are encouraging and have important medical implications for the first-line treatment of primary adenocarcinoma of the lung," stated Robert Pirker, M.D., Medical University of Vienna, Austria, and a member of the EJCMO Editorial Board.  "Confirmation of these important results in a well controlled Phase III trial would represent a major advance in the treatment of patients with advanced lung cancer."

Nicholas Thatcher, Professor in Medical Oncology at the University of Manchester and The Christie, England and EJCMO Editorial Board member said, "The potential to improve therapy in primary adenocarcinoma, the most common form of lung cancer, is an exciting possibility.  The results of the meta-analysis provide important support for a large scale confirmatory study of Tavocept on patient survival and the prevention of common chemotherapy side effects."

Michael C. Perry, M.D., M.A.C.P., Professor of Hematology and Medical Oncology, Nellie B. Smith Chair Emeritus, Ellis Fischel Cancer Center, University of Missouri-Columbia, co-author on the meta-analysis publication and a member of BioNumerik's Scientific Advisory Board said, "Despite some recent improvements, the 5-year overall survival rate for lung cancer is still only 15%. In addition, all currently approved survival-enhancing treatments for lung cancer are associated with common and serious toxicities that adversely impact the patient's quality of life, and in severe cases, can be fatal. The potential increase in survival represented by Tavocept would be a meaningful advance for patients, particularly if Tavocept is also able to prevent or reduce common and serious chemotherapy-induced side effects."

Dr. Hausheer added, "If we observe results in the ongoing Tavocept Phase III trial that are consistent with results observed for the Tavocept trials discussed in the meta-analysis publication, this would be a substantial potential advance compared to other recently developed first line lung cancer drugs.  For example, the cancer drug Avastin®, also known as bevacizumab, was approved in the United States to treat lung cancer while exhibiting a survival increase of approximately two months when used with a standard chemotherapy treatment regimen. The cancer drug Alimta®, also known as pemetrexed, when combined with cisplatin treatment in the first line setting, improved overall survival in primary adenocarcinoma patients by about 1.7 months.  Recent data for the cancer drug Erbitux®, also known as cetuximab, with chemotherapy demonstrated a survival increase of about 1.2 months compared to chemotherapy alone in patients with advanced epidermal growth-factor receptor (EGFR)-detectable non-small cell lung cancer. It is also important to consider that we have previously observed evidence of an overall survival treatment effect by Tavocept in both non-Asian and Asian populations; this is an important observation in consideration of the improved spectrum of activity of EGFR inhibitors in Asian patients and the potentially negative effect of some EGFR inhibitors on overall survival reported in Asian patients. By conducting this confirmatory Phase III Tavocept trial, we hope to improve survival in primary adenocarcinoma patients by a significantly greater margin than currently available treatments and at the same time prevent and mitigate chemotherapy induced anemia, kidney toxicity, nausea and vomiting, and peripheral nerve damage."

There are currently an estimated total of approximately 106 active Phase III oncology development programs worldwide throughout the entire life science industry. BioNumerik is conducting two global Phase III development programs, consisting of the Tavocept Phase III trial announced today and another Phase III development program for BioNumerik's novel drug candidate Karenitecin®, which is currently undergoing testing in a Phase III clinical trial in patients with advanced ovarian cancer. The Karenitecin Phase III trial is being conducted at approximately 86 clinical sites worldwide and is targeted to complete its enrollment by the end of 2010. BioNumerik holds exclusive rights to Tavocept and Karenitecin for all territories outside of Japan. BioNumerik has granted KI Pharmaceuticals, Inc., a joint venture formed by BioNumerik and ASKA Pharmaceutical Co., Ltd., the exclusive right to develop, market, distribute and sell Tavocept and Karenitecin in Japan.