Takeda Pharmaceutical Company Limited and BioNumerik Pharmaceuticals, Inc. have announced the results of two phase 3 trials for Tavocept. Tavocept is an investigational new drug with potential for oncology and non-oncology indications that was originated and developed by BioNumerik.

The initial development focus for Tavocept has been as an investigational new drug to prevent or mitigate the peripheral nerve damage, or neuropathy that is known to be associated with certain commonly used classes of chemotherapy drugs, such as taxane and platinum agents. Data was recently unblended by BioNumerik from two placebo controlled Tavocept phase 3 clinical trials, consisting of a phase 3 trial of weekly administration of paclitaxel (a widely used taxane drug) to patients, with metastatic breast cancer enrolled from the US, Russia, and Ukraine (the "Weekly Paclitaxel Breast Cancer Trial"); and a phase 3 trial involving administration of paclitaxel and cisplatin (a widely used platinum drug) every 3 weeks to patients with non-small cell lung cancer from Eastern and Western Europe. Both of these trials were aimed at evaluating Tavocept's potential for a neuropathy related treatment indication.

Each of the phase 3 trials was designed, as a randomized double-blind placebo controlled trial with each patient to be randomly assigned to receive either Tavocept or placebo in conjunction with chemotherapy. The primary endpoints for the Weekly Paclitaxel Breast Cancer Trial and the European Lung Cancer Trial were: The total incidence of severe neuropathy caused by the administration of chemotherapy in combination with Tavocept or placebo; and the difference in rates of tumour shrinkage in patients receiving chemotherapy in combination with Tavocept or placebo, in order to determine whether Tavocept has an impact on the anti-tumour effect of chemotherapy.

Based on review and analysis of the results, the trials did not meet their primary endpoints and they were inconclusive in terms of demonstrating a statistically significant effect of Tavocept in reducing the incidence of severe neuropathy caused by the administration of paclitaxel and cisplatin. In addition, neither of the trials demonstrated a statistically significant finding in terms of objective tumour response rate or tumour protection as assessed in accordance with the predefined statistical analysis plans for the trials, or by an independent radiological review committee.

In commenting on the data, Frederick H. Hausheer, MD, Chairman and CEO BioNumerik stated, "Many patients suffer from chemotherapy induced neuropathy and there is no FDA-approved treatment to prevent or reduce neuropathy caused by taxane and platinum chemotherapy drugs. Although we did not see the results that we hoped to observe in these phase 3 trials, we believe there is evidence of potential clinical activity of Tavocept that supports consideration of possible further Tavocept development aimed, at addressing the large unmet medical need for neuroprotective agents. Certain trends and subgroup analyses for the trials indicate that Tavocept may have potential for reducing chemotherapy induced neuropathy that merits consideration of further clinical testing. In addition, the way that neuropathy was measured and the countries where the trials were conducted may also has impacted the results."

"An important factor supporting possible future Tavocept development for a neuropathy indication is the subgroup analysis for patients enrolled only at clinical sites located in the US who participated in the Weekly Paclitaxel Breast Cancer Trial" said Hausheer. "We alsoobserved some encouraging trends in the Weekly Paclitaxel Breast Cancer Trial that indicate potential activity of Tavocept in reducing moderate to severe neuropathy. These are some of the first phase 3 trials conducted to assess the potential reduction of chemotherapy induced neuropathy. We believe there may be modifications in the trial endpoints in the future as well as changes in the procedures for assessing neuropathy in order to clinically assess patients at risk for this complication and to address some of the technical challenges we have observed in these trials to date. While we are encouraged by some of the observations in these trials, it is clear that additional clinical testing will be required to support development of Tavocept for a neuropathy indication."