FDA Oncologic Drugs Advisory Committee Recommends Marketing Approval for Ligand's Targretin Capsules for Treatment of Advanced-Stage Cutaneous T-Cell Lymphoma

Business Wire, Dec 13, 1999

SAN DIEGO--(BW HealthWire)--Dec 13, 1999--

--ODAC Declines to Recommend for Early-Stage Patients--

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced today that the Oncologic Drugs Advisory Committee (ODAC) of the U.S. Food and Drug Administration (FDA), by a vote of 13 to 2 (with one abstention), recommended marketing approval for Targretin(R) (bexarotene) capsules in the advanced-stage cutaneous T-cell lymphoma (CTCL) Stages IIb, III, IVa, IVb patient population as evaluated in Ligand's advanced-stage pivotal trial included in its new drug application (NDA). In a vote of 5 to 7 (with 4 abstentions), the committee declined to recommend marketing approval of Targretin capsules in the early-stage CTCL population as evaluated in its early-stage pivotal trial (Stages Ia, Ib, IIa).

The FDA is expected to consider the committee's recommendation for approval in its review of the NDA for Targretin capsules. While the FDA is not bound by the committee's decision, the agency usually follows committee advice. The FDA is expected to complete its review of the Targretin capsules NDA in December 1999. If Targretin capsule therapy is approved for marketing, it will be the first oral retinoid approved by the FDA specifically for the treatment of patients with CTCL.

"We are pleased with the panel's vote to recommend Targretin capsules approval for advanced-stage CTCL patients but disappointed that Targretin capsules was not also recommended at this time for the early-stage CTCL patient population," said David E. Robinson, Ligand Chairman, President and CEO. "We have worked closely with the FDA during this process, and we intend to have additional conversations with the FDA about the most appropriate patient populations for Targretin capsules following ODAC's recommendations including any additional information necessary for early-stage patients. The advanced-stage disease patient population, Stages IIb, III, IVa, IVb, are half or more of the prevalent patient population in the US and Targretin capsules will represent a significant therapeutic option as a new oral oncologic agent for them."

Other Committee Votes

Six questions were submitted to the committee for a vote. In addition to the primary questions of recommending approval of Targretin capsules in both early-stage and advanced-stage CTCL, the committee voted on four additional questions. The committee voted 11 to 4 (with one abstention) that a clinically meaningful tumor response rate using acceptable tumor response criteria had been adequately demonstrated and 0 to 14 (with two abstentions) that clinical benefit other than tumor response had been adequately demonstrated.

The committee voted as well on several other questions posed by the FDA including recommending an additional post approval/clinical study in advanced-stage patients.

"We are pleased that the FDA's ODAC panel has supported the conclusion from our data that Targretin capsules represent a positive risk benefit for advanced-stage CTCL patients," said Ligand Senior Medical Director and Physician Team Leader for the CTCL project, Richard C. Yocum, M.D. "The prompt and durable responses to Targretin capsule therapy are especially remarkable in this heavily pre-treated patient population with refractory CTCL and with few if any remaining treatment options. We look forward to continuing to work with the FDA to address requirements for approval in the early-stage disease patient population as well as commencing our dialogue on the recently submitted Targretin gel NDA in early-stage disease."

Targretin Capsules

The NDA for Targretin capsules was submitted by Ligand in June 1999 and was accepted for priority review by the FDA. Targretin has also received orphan drug designation in the U.S. In November 1999, Ligand submitted a Marketing Authorization Application (MAA) with the European Medicines Evaluation Agency (EMEA) seeking marketing clearance for Targretin capsules for the treatment of patients with CTCL. Ligand is conducting Phase II trials with Targretin capsules for the treatment of patients with moderate to severe plaque psoriasis and for the treatment of women with advanced breast cancer.

The NDA is based on the results from two multi-center, multinational clinical trials involving 152 patients with CTCL. The dose regimen recommended in the NDA is a single daily oral dose of Targretin capsules at an initial dose level of 300 milligrams per square meter (mg/m2) of body surface area, administered with a meal. In both clinical trials, this initial dose level provided efficacy that exceeded the protocol-defined targets of response rates.

Ligand has the worldwide rights to Targretin. If approved in the respective territories, Ligand expects to market and sell Targretin capsules in the U.S., Canada and selected European markets through its specialty oncology sales and marketing group. In Spain, Portugal, Greece, and Central and South America, Ferrer Internacional, S.A., will market and distribute, if approved in the respective jurisdictions, Targretin as well as certain other Ligand oncology products.