Takeda And BioNumerik .Phase III Trials Focused On Neuropath

[MsC1210]

Takeda And BioNumerik Announce Results Of Tavocept Phase III Trials Focused On Neuropathy Indication

01 Aug 2006

Takeda Pharmaceutical Company Limited ("Takeda," Osaka, Japan) and BioNumerik Pharmaceuticals, Inc. ("BioNumerik", San Antonio, Texas) today announced the results of two Phase III 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 unblinded by BioNumerik from two placebo controlled Tavocept Phase III clinical trials consisting of (1) a Phase III trial of weekly administration of paclitaxel (a widely used taxane drug) to patients with metastatic breast cancer enrolled from the United States, Russia, and Ukraine (the "Weekly Paclitaxel Breast Cancer Trial"); and (2) a Phase III 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 (the "European Lung Cancer Trial"). Both of these trials were aimed at evaluating Tavocept's potential for a neuropathy related treatment indication.

Each of the Phase III 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: (1) the total incidence of severe neuropathy caused by the administration of chemotherapy in combination with Tavocept or placebo; and (2) the difference in rates of tumor shrinkage in patients receiving chemotherapy in combination with Tavocept or placebo, in order to determine whether Tavocept has an impact on the anti-tumor 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/or cisplatin. In addition, neither of the trials demonstrated a statistically significant finding in terms of objective tumor response rate or tumor 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, M.D., Chairman and Chief Executive Officer of 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 III 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 have impacted the results."

Subgroup analysis by country from the Weekly Paclitaxel Breast Cancer Trial revealed a notable finding in favor of Tavocept in the reduction of patient-reported severe neuropathy (as measured by Patient Neurotoxicity Questionnaire (PNQ) grades D or E) for patients enrolled only from U.S. sites. In this subpopulation comprising patients enrolled only from U.S. sites, the incidence of patient-reported severe neuropathy confirmed for at least 4 weeks (PNQ grades D or E) was 3.2% in the Tavocept group as compared to 20.0% in the placebo group. This observation represents an 84% lower incidence of severe neuropathy in favor of Tavocept. The Patient Neurotoxicity Questionnaire (or PNQ) is a patient-based neuropathy measurement tool that was used to measure neuropathy in the Tavocept Phase III trials. The National Cancer Institute Common Toxicity Criteria ("NCI-CTC"), a physician-based neuropathy measurement tool, showed a consistent trend with that of the PNQ in terms of comparing the overall severe neuropathy reported in the Tavocept and placebo arms for patients from U.S. sites in the Weekly Paclitaxel Breast Cancer Trial. However, it is also important to note that only about 8% of the total number of patients treated in the Weekly Paclitaxel Breast Cancer Trial were treated at U.S. clinical sites.

"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 United States who participated in the Weekly Paclitaxel Breast Cancer Trial," said Hausheer. "We also observed 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 III 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."

Takeda has notified BioNumerik that, given the additional time necessary to conduct additional clinical testing for a Tavocept neuropathy indication, one possible alternative is termination of the existing Tavocept License and Development Alliance Agreement between Takeda and BioNumerik for the United States and Canada. Takeda and BioNumerik are continuing to discuss the data from the trials as well as considerations regarding the alliance agreement and the future development of Tavocept.

About Tavocept:

Tavocept is an investigational new drug with potential for oncology and non-oncology indications that was originated and developed by BioNumerik. Tavocept has potential applicability in multiple therapeutic areas including diabetic neuropathy, protection against toxicity from radiation therapy, lymphedema and other potential medical indications. In addition to chemotherapy induced neuropathy, BioNumerik is evaluating further Tavocept development possibilities in these areas.

About Takeda:

Takeda, located in Osaka, Japan, is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. Additional information about Takeda is available through its corporate website, http://www.takeda.com/index-e.html.

About BioNumerik:

BioNumerik, headquartered in San Antonio, Texas, is a pharmaceutical company focused on the discovery, development and commercialization of novel drugs for the treatment of patients with cancer. BioNumerik has two drug candidates in late-stage clinical development: Tavocept and Karenitecin (BNP1350).

BioNumerik Pharmaceuticals; Takeda Pharmaceutical Company http://www.takeda.com/index-e.html

Article URL: http://www.medicalnewstoday.com/medical ... wsid=48391

[RandyW]

Thanks for posting This it looks promising so far and sounds promising as well.

[MsC1210]

Hi Randy,

No thanks needed, I pray that this will be of some use to someone, if only to add a ray of HOPE.

Hugs

Chris