Armed with promising early results of its small-molecule candidate, pralatrexate (PDX), in a patient population for which there is no approved therapy, Allos Therapeutics Inc. reached a special protocol assessment agreement with the FDA for a pivotal Phase II study.

Results of the trial are expected to provide the basis for a new drug application for PDX in patients with relapsed or refractory peripheral T-cell lymphoma.

"No agents have been approved for use in that setting," said Jennifer Neiman, corporate communications manager of Westminster, Colo.-based Allos. "Physicians really struggle to find one or more agents that can be effective."

PDX is a small-molecule chemotherapeutic product designed to inhibit dihydrofolate reductase. Last week, the FDA gave the product orphan status. PTCL is a fairly rare disease and accounts for about 10 percent to 15 percent of all non-Hodgkin's lymphoma cases, with an estimated 6,700 PTCL patients in the U.S.

Allos was given the nod largely based on interim results from a Phase I/II study reported in December at the 2005 American Society of Hematology meeting in Atlanta. Those data showed that four of seven evaluable patients with T-cell lymphoma who had failed multiple prior therapies achieved a complete response following treatment with PDX.

"Those results were significantly compelling to warrant a subsequent discussion with the FDA," Neiman told BioWorld Today.

The SPA calls for a non-randomized, open-label study expected to involve about 100 patients at 35 cancer centers in the U.S., Canada and Europe. All patients will receive 30mg/m2 of PDX once a week for six weeks, followed by one week of rest per cycle of treatment. All also will concurrently receive vitamin B12 and folic acid supplementation.

The primary endpoint is response rate. Though the company hasn't specified a rate needed for approval, Neiman said a "20 percent response rate is considered a good barometer of activity," as seen with previously approved drugs.

Cambridge, Mass.-based Genzyme Corp. gained approval of Clolar (clofarabine) in 2004 in pediatric relapsed or refractory acute lymphoblastic leukemia based on a response rate of 20 percent. In 2005, London-based GlaxoSmithKline plc received approval of Arranon (nelarabine) which demonstrated a 22 percent response rate in adults and children with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. (See BioWorld Today, Dec. 30, 2004.)

"And when we looked at those other niche hematologic agents that have achieved approval, we found that they did so with comparably designed single-arm trials," Neiman said.

Allos plans to begin the study this quarter, but beyond that hasn't provided a timeline for getting the product to market.

"It's difficult to say, given that there haven't been many multicenter trials conducted in this patient population," Neiman said, though she added that "we think it will take about a year and a half to two years to complete patient enrollment."

At this time, Allos holds all the rights to PDX, with no plans to partner. Instead, the company intends to build its own specialty sales force to market both PDX and its lead product Efaproxyn (efaproxiral), which is nearing the end of a pivotal Phase III study.

Efaproxyn is a synthetic small molecule designed to sensitize hypoxic tumor tissue during radiation therapy and is being developed as an adjunct to whole-brain radiation therapy in women with brain metastases that originated from breast cancer.

Neiman said Allos expects to complete enrollment soon in the Efaproxyn study, with an interim analysis planned in the second half of the year.

Shares of Allos (NASDAQ:ALTH) closed at $3.74 Wednesday, up 3 cents.