Allos Therapeutics Submits New Drug Application for Pralatrexate for Patients with Relapsed or Refractory Peripheral T-cell Lymphoma

Allos Therapeutics, Inc. today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the use of pralatrexate for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The Company has requested a priority review of the application, which, if granted, would give the FDA six months from receipt of the submission to take action on the application. PTCL comprises a biologically diverse group of hematologic malignancies that typically has a worse prognosis than other types of lymphoma and is less responsive to traditional chemotherapy regimens. There are currently no agents approved by the FDA for the treatment of patients with PTCL.

“The NDA submission is based on the encouraging efficacy and safety data we reported earlier this year with pralatrexate in patients with relapsed or refractory PTCL,” said Paul L. Berns, president and chief executive officer of Allos Therapeutics, Inc. “We plan to work closely with the FDA to facilitate the completion of their review as expeditiously as possible. There are currently no agents approved by the FDA for the treatment of patients with PTCL, which demonstrates the clear, high-unmet need for new therapies to treat patients with this devastating disease. If approved, pralatrexate represents a potential first-to-market opportunity for Allos and could be the first agent approved by the FDA for the treatment of patients with relapsed or refractory PTCL.”

The NDA is based on the results from the Company’s pivotal Phase 2 trial known as PROPEL (Pralatrexate in patients with Relapsed Or refractory PEripheral T-cell Lymphoma). The PROPEL trial was conducted under an agreement reached with the FDA under its Special Protocol Assessment, or SPA, process. Pralatrexate has orphan drug designation and fast track designation in the U.S. for the treatment of patients with T-cell lymphoma and orphan medicinal product designation in Europe for the treatment of PTCL. The Company believes the PROPEL trial is the largest prospectively designed single-agent trial conducted to date in patients with relapsed or refractory PTCL.

About PROPEL

This pivotal Phase 2 international, multi-center, open-label, single-arm trial enrolled a total of 115 patients with relapsed or refractory PTCL, 109 of whom are considered evaluable for response, according to the trial protocol. To be eligible for the trial, patients’ disease must have progressed after at least one prior treatment. Patients were considered evaluable if they received at least one dose of pralatrexate and their diagnosis of PTCL was confirmed by independent pathology review. Patients received 30 mg/m2 of pralatrexate intravenously once every week for six weeks followed by one week of rest per cycle of treatment. Patients also received vitamin B12 and folic acid supplementation. The primary endpoint of the trial is objective response rate, as assessed by central independent oncology review using International Workshop Criteria (IWC). Duration of response is the key secondary endpoint.

In February 2009, the Company announced final results from the PROPEL trial. Twenty-nine of 109 evaluable patients, or 27 percent, achieved a response as assessed by central independent oncology review, which is the primary endpoint of the trial. The Kaplan-Meier estimate for the median duration of response was 287 days, or 9.4 months. Duration of response is the key secondary endpoint of the trial. The most common grade 3/4 adverse events were thrombocytopenia, which was observed in 32 percent of patients; mucosal inflammation in 21 percent of patients; neutropenia in 20 percent of patients; and anemia in 17 percent of patients. The results of the trial will be submitted for presentation at an upcoming scientific meeting and for publication in a peer-reviewed journal.

Of the 29 patients who achieved a response according to central independent oncology review, 7 patients had a complete response (CR), 2 patients had a complete response unconfirmed (CRu) and 20 patients had a partial response (PR). Responses were also assessed by the PROPEL investigators, who determined that 42 of 109 evaluable patients, or 39 percent, achieved a response. Of these, 15 patients had a CR, 4 patients had a CRu and 23 patients had a PR. PROPEL patients received a median of three prior systemic treatment regimens (range of 1-12), including 18 patients, or 16 percent, who had previously undergone an autologous stem cell transplant. In the trial, 66 percent of the patients who responded did so after cycle one of therapy. Patients will continue to be followed for long-term survival.

The PROPEL trial is being conducted under an agreement reached with the FDA under its SPA process. The SPA process allows for FDA evaluation of a clinical trial protocol intended to form the primary basis of an efficacy claim in support of an NDA, and provides an agreement that the trial design, including trial size, clinical endpoints and/or data analyses are acceptable to the FDA. The response rate, duration of response and safety profile required to support FDA approval are not specified in the PROPEL trial protocol and will be subject to FDA review. In addition, the median duration of response reported above is a Kaplan-Meier estimate based on the length of follow up for all responders at the time the PROPEL trial database was locked. As a result, the median duration of response may change based on continued patient follow-up.

Source : www.businesswire.com