Tolero Pharmaceuticals reports positive interim results from alvocidib Phase 2 trial for AML treatment

Tolero Pharmaceuticals, Inc., a late clinical-stage biopharmaceutical company developing treatments for oncology and blood disorders, reported positive interim results from an ongoing, randomized Phase 2 clinical trial of its lead drug candidate, alvocidib, in combination with cytarabine plus mitoxantrone for previously untreated acute myeloid leukemia (AML) patients. In this clinical trial, which was presented by Joshua Zeidner, M.D., from Johns Hopkins University, patients with newly diagnosed, poor and intermediate risk AML, experienced complete response (CR) rates of 70% versus 46% with the standard of care (p=0.003). These data were reported at the 2014 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"The data presented at ASCO are compelling and suggest to us that the combination of alvocidib with cytarabine plus mitoxantrone is well tolerated and highly active when compared to available therapies," said Gerald Messerschmidt, M.D., FACP, Senior Vice President of Clinical Affairs at Tolero. "We are encouraged to see newly diagnosed, poor-risk AML patients in this trial achieve higher complete response rates compared to the standard of care. We are also pleased that many of these responses remain durable."

The trial was led by Johns Hopkins University and enrolled 165 patients across 10 participating institutions. The trial compared alvocidib in combination with cytarabine plus mitoxantrone to cytarabine plus daunorubicin, a regimen that is also known as "7+3." The study had a 2:1 randomization (two patients on the alvocidib combination for every patient on cytarabine plus daunorubicin) with patients stratified by age, secondary AML and leukocyte count. Fourteen days post treatment, patients on the 7+3 arm with residual leukemia received a second round of "induction" therapy, referred to as "5+2," whereas patients treated with the alvocidib combination received just one induction therapy.

The primary endpoint of the trial was to compare CR rates of one cycle of the alvocidib combination therapy with CR rates of one cycle of 7+3. Secondary endpoints include safety, CR rates after one cycle of alvocidib combination therapy versus CR rates after 7+3 plus 5+2, overall survival (OS) and disease-free survival (DFS). More patients receiving the alvocidib combination achieved CR compared to those who received the standard of care with 7+3 (70% versus 46%, p=.003). Additionally, patients with secondary AML who received alvocidib also experienced higher rates of CR (60% versus 35%, p=0.05). Induction with the alvocidib containing regimen achieved significantly higher CR rates compared to 7+3 with no meaningful increase in serious toxicities.

The last patient in this trial was dosed in August 2013. While the overall survival data are still maturing, Kaplan-Meier estimates of continuing survival out to 30 months suggest long-term durable responses in patients treated with the alvocidib combination.

"The high CR rates observed using alvocidib combination therapy in this most recently completed clinical trial provide strong support for further clinical investigation," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero. "In addition, the trial is a positive step in advancing a new treatment option in a disease which is difficult to treat and where patients and physicians have not had a new treatment option in nearly four decades."

Alvocidib has been evaluated in five Phase 2 clinical trials, involving more than 400 patients with AML. Based on these and other results, Tolero is planning further development of alvocidib in previously untreated intermediate and high-risk patients with AML and relapsed/refractory AML.

"The positive results from this trial lend further credibility to Tolero's licensing, drug discovery and development capabilities, which is being advanced in order to address high unmet medical needs in oncology, including through novel mechanisms. I am excited to be working with Tolero as an advisor to their clinical development efforts," said Daniel D. Von Hoff, M.D., Senior Science Advisor to Tolero.