Washington Editor

BioCryst Pharmaceuticals Inc. is set to begin a pivotal trial of its lead cancer compound, Fodosine (forodesine hydrochloride), by the end of this year after agreeing to a special protocol assessment from the FDA.

The study will evaluate two formulations of the drug simultaneously, an intravenous version for early, acute treatment followed by maintenance therapy with an oral form of an equivalent dose. Fodosine, a transition-state analogue inhibitor that targets the purine nucleoside phosphorylase (PNP) enzyme, will be tested in about 100 patients who have failed two or more previous induction therapies for acute lymphoblastic T-cell leukemia/lymphoma.

The multicenter, open-label, nonrandomized, repeat-dose study is designed to determine the rate of complete remission achieved with that regimen of Fodosine as the primary endpoint. Questions as to whether the single-arm design would support approval were satisfied during the SPA process, BioCryst Chairman and CEO Charles Bugg told BioWorld Today. "We have clear acknowledgment of that."

The performance of Fodosine, a cytostatic agent with a favorable, non-toxic side-effect profile, will be measured against historical outcomes. Recent FDA approvals of other leukemia drugs have been based on 20 percent remission rates, and past clinical studies of Fodosine have demonstrated 20 percent to 30 percent rates.

In the trial, patients will receive six weeks of intravenous dosing, followed by a switch to daily oral therapy if disease progression has halted. "We're viewing the oral [formulation] as a chronic treatment," Bugg said, later likening that long-term therapy goal to similar maintenance dosing with Gleevec (imatinib, from Novartis AG). Secondary endpoints include assessing the safety and tolerability of extended daily treatment with the regimen, determining its effects on survival endpoints and evaluating the maintenance of response.

"Back-and-forth" negotiations between the company and the FDA took 10 months before both parties finalized the protocol, Bugg said. Ultimately, if the trial succeeds, the company would submit two new drug applications, one for the intravenous formulation and another for the oral version. However, the Birmingham, Ala.-based company has not provided guidance on a timeline for finishing the study or filing for approval.

Patients with acute lymphoblastic T-cell leukemia/lymphoma often receive initial treatment with chemotherapy, followed by experimental products if cytotoxic therapy fails. The FDA recently approved a T-cell leukemia drug, Arranon (nelarabine, from GlaxoSmithKline plc).

Fodosine also is being studied in clinical trials including cutaneous T-cell lymphoma, B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. Abstracts from those studies are being submitted for presentation at the American Society of Hematology meeting, and the next stage of pivotal work on the drug will center on cutaneous T-cell lymphoma.

Its development in Europe, Asia and Australia is moving forward in collaboration with Mundipharma International Holdings Ltd., a company principally focused on chronic lymphocytic leukemia and acute myelogenous leukemia. Bugg said that Cambridge, UK-based Mundipharma offered considerable input in this pivotal trial design and expects that it also could support approval in Europe. The deal between the partners potentially is worth $190 million. (See BioWorld Today, Feb. 3, 2006.)

Beyond Fodosine, BioCryst is advancing a second-generation PNP inhibitor, BCX-4208, for transplantation and autoimmune diseases through a worldwide partnership with Basel, Switzerland-based F. Hoffmann-La Roche Ltd. worth up to $560 million. That product is in Phase I. Its other principal products include peramivir for seasonal and pandemic flu, which is entering Phase II in the coming flu season, as well as BCX-4678 for hepatitis C, for which an investigational new drug application is on the not-too-distant horizon.

On Monday, the company's stock (NASDAQ:BCRX) gained 6 cents to close at $11.12.