Hana Biosciences, a biopharmaceutical company focused on advancing cancer care, has announced the initiation of a multicenter phase II clinical trial with Talvesta (talotrexin) for Injection in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

The primary objective of this phase II portion of an ongoing phase I/II open-label study is to evaluate the complete remission rate (CR/CRp) of Talvesta in relapsed or refractory ALL patients. Secondary objectives are to evaluate the safety and tolerability of Talvesta in this setting as well as duration of complete remission and overall survival. Data from the phase I portion of this clinical trial will be presented during the 48th annual American Society of Hematology (ASH) meeting in December in Orlando, Florida, on Sunday, December 10th.


"We are pleased to advance Talvesta into a phase II trial in adults with relapsed ALL, a disease with few effective therapeutic options," commented Greg Berk, MD, senior vice president and chief medical officer of Hana Biosciences. "We look forward to presenting the phase I data at ASH in December, and are excited to have recruited several major leukemia referral centers into this important trial."

Talvesta is a novel, nonpolyglutamable antifolate drug which targets Dhfr under development for the treatment of various types of cancers. Talvesta has demonstrated enhanced antitumor activity in a broad spectrum of preclinical studies by targeting the enzyme Dhfr to prevent DNA synthesis in tumour cells and inhibit tumour growth. These studies suggest that Talvesta, as compared to other antifolates, enters into cells up to ten times more efficiently and demonstrates 10 to 100 fold more potency in overcoming polyglutamation, a well-established mechanism of antifolate resistance. Talvesta also binds more tightly to its anti-tumour target Dhfr, which Hana believes may further inhibit tumour growth. In May 2006, the US Food and Drug Administration granted orphan drug designation for Talvesta in patients with ALL. In addition, Talvesta is also being studied in a phase I in solid tumours and a phase I/II in non-small cell lung cancer (NSCLC).

Approximately 4,000 cases of ALL are diagnosed annually in the US. While cure rates for childhood ALL have steadily improved to nearly 90 per cent, adult ALL reported cure rates seldom exceed 40 per cent. The poorer outcome in adult ALL has been attributed to an increased frequency of high-risk leukemia with greater resistance, poorer tolerance of and compliance with treatment, reluctance to accept toxic effects, and less effective treatment regimens as compared with childhood ALL. Currently, there are no approved agents for adult ALL salvage, nor is there a consensus on the most appropriate regimen in the relapse setting. Ongoing efforts are needed to investigate agents for this indication, as well as incorporate active agents, once identified, into frontline therapy.