INNOVIVE Pharmaceuticals Initiates Pivotal Phase II Clinical Trial With Tamibarotene

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Clinical Trials / Drug Trials
Article Date: 16 Nov 2007 - 12:00 PDT

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INNOVIVE Pharmaceuticals, Inc. (OTCBB:IVPH) announced that the first patient has been treated in a pivotal Phase II clinical trial evaluating oral Tamibarotene for the treatment of refractory acute promyelocytic leukemia (APL). APL is a type of acute myeloid leukemia. This trial will be conducted under a Special Protocol Assessment (SPA) agreed upon by INNOVIVE and the U.S. Food and Drug Administration (FDA) in August. In conjunction with data from Japanese studies, data from INNOVIVE's pivotal study of Tamibarotene are expected to form the basis of a New Drug Application (NDA) with the FDA.

Approved in Japan in 2005 for treatment of recurrent APL, Tamibarotene was designed to meet the need of patients for whom treatment with the current first-line standard of care, all-trans-retinoic acid (ATRA), is not effective and to provide a less toxic alternative to ATRA. Since approval in Japan, more than 200 patients have been safely treated with Tamibarotene.

"The data from trials conducted in Japan suggest that Tamibarotene is effective in patients who have failed previous ATRA-based therapy," stated Jorge Cortes, M.D., internist and professor of medicine at The University of Texas MD Anderson Cancer Center and lead principal investigator in the trial. "We believe there is significant unmet medical need in refractory APL patients. We are evaluating Tamibarotene in patients that have failed both ATRA and arsenic trioxide to determine whether Tamibarotene could provide a better treatment option in this setting."

Known as STAR-1 (A Phase II Study of Oral Tamibarotene in Acute Promyelocytic Leukemia Patients who Have Received Prior Therapy with ATRA and Arsenic Trioxide), this open-label, non-randomized, single-arm, multi-national study will enroll 50 adult patients with relapsed or refractory APL following treatment with ATRA and arsenic trioxide. Tamibarotene will be self-administered orally via tablets on an outpatient basis at a dose of 6 mg/m2 per day.

The primary objective of the study is to determine the rate of durable complete response for Tamibarotene therapy when administered as a single agent to adult patients with relapsed or refractory APL. Secondary objectives are to determine the rates of morphologic leukemia-free state, partial response, cytogenetic complete response, and molecular complete response and to determine the safety profile, tolerability, and pharmacokinetic profile of Tamibarotene in the indicated patient population.

"The STAR-1 study will provide important insights about the potential for Tamibarotene to circumvent the resistance and toxicity issues that limit effectiveness of existing retinoic acid therapies in APL," said Martin Tallman, M.D., professor of oncology at Northwestern University Feinberg School of Medicine and principal investigator in the trial.

Additional information regarding the design, enrollment criteria, and participating centers for the pivotal Phase II trial with Tamibarotene in refractory APL is available at http://www.APLtrial.com or http://www.clinicaltrials.gov (keyword: Tamibarotene).

About APL

Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia, a cancer of the blood and bone marrow. In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The accumulation of promyelocytes in the bone marrow results in a reduction in the production of normal red blood cells and platelets resulting in anemia and thrombocytopenia. Either leukopenia (low white cell count) or leukocytosis (high white cell count) may be observed in the peripheral blood. Symptoms include fatigue, weakness, shortness of breath from anemia, easy bruising and bleeding from thrombocytopenia and coagulopathy, and fever and infection from lack of normal white blood cells.

ATRA is the current standard of care for the first-line treatment of APL in combination with chemotherapeutic agents. ATRA has been associated with retinoic acid syndrome (RAS), a serious and sometimes fatal complication that occurs in up to 25 percent of patients due to a rapid increase in white blood cells. Duration of remission induced by treatment with ATRA alone is typically short. In addition, patients often fail to respond to a second course of treatment with ATRA. Currently, patients who fail ATRA-based therapy are treated with arsenic trioxide, a compound administered intravenously and associated with significant toxicity including irregular heartbeat. There is no standard of care for patients who do not respond to ATRA and arsenic trioxide.

About Tamibarotene

Tamibarotene is a fully synthetic retinoid developed to specifically overcome resistance to ATRA and is currently approved in Japan for treatment of relapsed/refractory APL. In conjunction with data from Japanese studies, data from INNOVIVE's pivotal study of Tamibarotene are expected to form the basis of a New Drug Application (NDA).

In vitro, Tamibarotene is approximately 10 times more potent than ATRA at causing APL cells to differentiate and die. Tamibarotene has a lower affinity for cellular retinoic acid binding protein, or CRABP, which is believed to allow for sustained plasma levels during administration. Tamibarotene does not bind the RAR-γ receptor, the major retinoic acid receptor in the dermal epithelium. This suggests that Tamibarotene therapy may lead to fewer adverse events compared to ATRA. In Phase II clinical studies conducted in Japan, the rate of RAS appeared to be low.

In a pivotal Phase II study conducted in Japan, the effectiveness of orally administered Tamibarotene was evaluated daily for eight weeks in 39 Japanese patients with APL, including treatment-naïve and previously treated patients. The overall response rate in these patients was 61.5 percent. In patients with recurrent disease, the overall response rate was 81 percent. RAS was reported in 7.3 percent of patients. An additional Phase III study is currently underway in Japan comparing ATRA to Tamibarotene for the maintenance treatment of APL.

In December 2006, INNOVIVE acquired the exclusive North American license from TMRC, Co., Ltd. to develop and commercialize Tamibarotene in the United States for treatment of APL, with an option to include within the license the use of Tamibarotene in other fields in oncology including multiple myeloma, myelodysplastic syndrome, and solid tumors. In September 2007 INNOVIVE acquired the exclusive European license from TMRC to develop and commercialize Tamibarotene in Europe for treatment of APL, with an option to include within the license the use of Tamibarotene in other oncology disease areas including multiple myeloma, myelodysplastic syndromes and solid tumors, except hepatocellular carcinoma.

About INNOVIVE Pharmaceuticals

INNOVIVE Pharmaceuticals, Inc. acquires, develops and commercializes novel therapeutics addressing significant unmet medical needs in the fields of oncology and hematology. The company has four drug programs in clinical development: INNO-406, Tamibarotene, INNO-206, and INNO-305, for the treatment of chronic myelogenous leukemia, acute promyelocytic leukemia, small cell lung cancer, and acute myelogenous leukemia, respectively. For additional information visit http://www.innovivepharma.com.

Forward-looking Statements

This material contains forward-looking statements as defined by the Private Securities Litigation Reform Act of 1995. These include statements concerning plans, objectives, goals, strategies, future events or performance and all other statements which are other than statements of historical fact, including without limitation, statements containing words such as "believes," "anticipates," "expects," "estimates," "projects," "will," "may," "might" and words of a similar nature. Such statements involve risks and uncertainties that could cause actual results to differ materially from those projected. Among other things, there can be no assurances that any of INNOVIVE's development efforts relating to its product candidates will be successful. Other risks that may affect forward-looking information contained in this press release include the risk that the results of clinical trials may not support INNOVIVE's claims, the possibility of being unable to obtain regulatory approval of INNOVIVE's product candidates, INNOVIVE's reliance on third party researchers to develop its product candidates and its lack of experience in developing pharmaceutical products. These and other risks are discussed in INNOVIVE'S periodic reports filed with the SEC. The forward-looking statements contained herein represent the judgment of INNOVIVE as of the date this material was drafted. INNOVIVE disclaims, however, any intent or obligation to update any forward-looking statements.

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