[gdpawel]

I remember writing five years ago about Bionumerik boosting about its new drug Tavocept, that was aimed at preventing or reducing common and serious side effects, particularly nerve and kidney damage, associated with taxane and platinum drugs. Very little had been accomplished to prevent or reduce chemotherapy-induced toxicities, but they had a new product and began testing it.

BioNumerik Launches Phase III Trial To Confirm Surprising Tavocept Survival Benefit In NSCLC
The Pink Sheet Daily. 2010 Jan 21, S Haley

Buoyed by the discovery that a molecule it set out to test for its chemoprotective qualities appears to confer as much as a 6.7 month survival advantage to the sickest of lung cancer patients, BioNumerik has launched a global Phase III confirmatory trial testing a Tavocept regimen in first-line treatment of advanced adenocarcinoma of the lung, the company announced Jan. 21.

The global trial will enroll patients at 80-100 clinical sites in the U.S., Russia, Ukraine, Eastern Europe and Latin America to test Tavocept (BNP7787) in combination with taxane and cisplatin chemotherapy against taxane and cisplatin alone. The primary endpoint is overall survival, with the goal of establishing the small-molecule drug as a first-line treatment for the most common form of non-small cell lung cancer. BioNumerik expects the study to be fully enrolled by the end of this year.

Tavocept's ability to prevent or mitigate chemotherapy-induced toxicities will be evaluated as secondary endpoints. If the trial is successful, Tavocept will offer oncologists a small-molecule option that is effective in both Asian and non-Asian populations and offers both a survival advantage and reduced side-effects, says BioNumerik CEO Frederick Hausheer.

To substantiate the new Phase III effort, BioNumerik conducted a meta-analysis of data from two smaller randomized, controlled trials of Tavocept in chemotherapy-naive patients with advanced NSCLC treated with taxane plus cisplatin, or chemo alone. The study, published in the December issue of the European Journal of Clinical & Medical Oncology, concludes that among patients with newly diagnosed (inoperable) stage IIIB/IV primary adenocarcinoma of the lung, non-Asian patients had a significant 6.7 month increase in overall survival (p=0.0326) and Asian patients had a "strong non-significant" 4.6 month increase compared to chemo alone (p=0.0720).

The study also found a significant one-year survival benefit in favor of Tavocept in both studies separately and combined. Combined, the studies showed a statistically significant improvement in overall survival (p=0.009) in favor of the Tavocept arms, representing an approximate 7.7 month increase in overall survival, with 68 percent of Tavocept-treated patients alive at one year versus 48 percent of control (p=0.003).

The meta-analysis examined combined survival outcomes for 346 patients in the two trials, in the U.S. and Japan, including 211 patients with primary adenocarcinoma. The result for Asian patients, from a study conducted in Japan by BioNumerik's Tokyo-based development partner ASKA Pharmaceutical, is particular important because of missteps with programs like AstraZeneca's Iressa (gefitinib), which was active in the Asian population, but not in non-Asians, Hausheer pointed out.

New Tool For Measuring Neurotoxicity After Failure

BioNumerik is entering this new round of inquiry armed with a validated instrument for measuring the effects of chemotherapy-induced neuropathy, after Tavocept failed to meet that endpoint in the earlier U.S. study ('The Pink Sheet' DAILY, March 16, 2008).

Chemo-induced neuropathy can manifest itself not only as sporadic neurotoxic events, but also in persistent form, which affects a little over half of patients, explained Hausheer. By looking for neurotoxic events in two consecutive treatment cycles, according to the study design requested by FDA, "we basically were throwing away about 40 to 50 percent of the sample, and that's why it didn't meet its endpoints," he said. The new study will use the Patient Neurotoxicity Questionnaire, which has been validated in randomized trials.

As well as preventing neuropathy, which is largely irreversible once it manifests, Tavocept appears to reduce the severity of renal toxicity from cisplatin, as well as nausea/vomiting and anemia, Hausheer said.

One of the biggest opportunities is in anemia, said Hausheer. While the standard for chemo-related anemia treatment used to be erythropoietin-stimulating agents, safety concerns with ESAs have left a need in the market. Blood transfusions carry a 25 to 30 percent increase in the risk of thromboembolism, Hausheer added.

Not having to worry so much about anti-emetics also appeals to oncologists, Hausheer said. And, if renal toxicity from cisplatin is under control, the regimen could be given in the outpatient setting very conveniently, instead of "having to give patients all that saline hydration," he added.

Privately held BioNumerik is currently discussing Tavocept with potential alliance partners, Hausheer said.