BioCryst Pharmaceuticals announced long-term data from a Phase 2 study of forodesine, the Company's lead oncology compound, in patients with cutaneous T-cell lymphoma (CTCL).
The data will be presented at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held in Orlando, Florida from May 29-June 2. Forodesine is a transition-state analog inhibitor of purine nucleoside phosphorylase (PNP), a purine salvage pathway enzyme that is essential for the proliferation of T-cells and B-cells.

The poster entitled "Long-Term Treatment of CTCL with the Oral PNP Inhibitor, Forodesine" (Abstract #8552, M. Duvic et. al.) will be in a general ASCO poster session on Saturday, May 30 from 8 a.m. to 12 p.m. Eastern Time on Level 2, West Hall C, Board Q18 of the Orlando Convention Center.

The open-label, dose escalation study evaluated 40-320 mg/m2 of forodesine given once-daily for four weeks to determine the maximum tolerated dose and optimal biologic dose (OBD). The OBD was determined to be 80 mg/m2 of forodesine. Additional patients were enrolled in this trial to further assess the long-term safety and clinical efficacy at the 80 mg/m2 dose level. The primary efficacy endpoint was objective response rate, defined as greater than or equal to a 50 percent improvement by a severity-weighted assessment tool.

The overall response rate in the intent to treat population was 17 of 64 patients (27 percent), including 14 of 36 patients (39 percent) treated with the 80 mg/m2 dose. As of October 2008, nine of 64 patients (14 percent) received forodesine treatment for greater than 12 months. Of these nine patients, six discontinued treatment. Four patients discontinued treatment because of progressive disease, one withdrew consent and one discontinued due to an adverse event (diffuse large b-cell lymphoma). The median time on treatment for these six patients was 440 days. Through October 1, 2008, the other three patients remained on therapy for 416, 710 and 863 days, respectively.

"This Phase 2 trial further shows the safety and efficacy of an oral PNP inhibitor, forodesine, for CTCL patients of all stages who have failed standard therapies," said Madeleine Duvic, M.D., Professor of Medicine and Dermatology, Deputy Chairman, Department of Dermatology at the MD Anderson Cancer Center.

"We believe these data further support the clinical utility of forodesine as a treatment for CTCL and are encouraged by its safety and efficacy profile in this study," said Dr. William P. Sheridan, BioCryst's Chief Medical Officer. "We continue to actively enroll patients in our pivotal Phase 2 study of forodesine in patients with CTCL and look forward to results from this study in the first half of next year."

Of the nine patients that received forodesine treatment for 12 or more months, the most frequent adverse events were nausea (44 percent), fatigue (22 percent), peripheral edema (22 percent), dyspnea (22 percent) and urinary casts (22 percent). Grade 3 or higher adverse events were diffuse large B-cell lymphoma and peripheral edema. There were no hematologic or infection adverse events related to forodesine. Grade 3 lymphopenia and a CD4 count of less than 200 were noted in eight of the nine subjects and four of the nine subjects, respectively.

BioCryst is a biopharmaceutical company that has developed a pipeline of novel therapeutics targeting major illnesses by employing crystallography and structure-based drug design.