Ligand Receives FDA Marketing Clearance for Bexarotene Gel

The US Food and Drug Administration (FDA) has granted marketing clearance for bexarotene (Targretin) gel 1%, a novel therapy for the topical treatment of cutaneous lesions in patients with early-stage (IA and IB) cutaneous T-cell lymphoma (CTCL) who develop refractory or persistent disease after undergoing other therapies or who have not tolerated other therapies. Developed by Ligand Pharmaceuticals Inc, bexarotene gel is the first and only topical therapy approved by the FDA for the treatment of CTCL.

Because it is topically applied, the new dosage form of bexarotene offers patients with CTCL a noninvasive, self-administered treatment that is directed only to the affected areas of the skin. Other currently available but unapproved treatments for early-stage CTCL, including mechlorethamine (Mustargen) and carmustine (BCNU), may be limited by allergic hypersensitivity reactions, commercial availability, and an increased risk of secondary skin cancers.

Simpler Administration

Unlike bexarotene gel, topical mechlorethamine is generally applied to skin over the entire body; this can be a time-consuming and difficult task for many patients. Many other current therapies for CTCL, such as electron-beam treatment, photopheresis, and psoralen plus UV-A light (PUVA), require administration by health-care professionals and, therefore, frequent visits to a clinic, hospital, or doctor’s office.

The FDA based its decision to approve bexarotene gel on a multicenter, open-label phase III clinical trial that was conducted in 50 patients in the United States, Canada, Europe, and Australia; a phase I/II clinical program involving 67 patients; and supporting data from 200 patients with CTCL treated with bexarotene capsules. Efficacy results in the phase III trial exceeded the protocol-defined response rate target. Side effects were limited primarily to local skin reactions and included rash, itching, skin disorder, and pain.

“Patients studied in the phase III clinical trial for Targretin gel failed at least two prior therapies and often had received multiple other treatments,” said Steven D. Reich, md, senior vice president of clinical research for Ligand. “Targretin gel can provide patients with early-stage CTCL a treatment alternative that is both effective and generally well tolerated in managing the cutaneous manifestations of CTCL, a progressive and symptomatic disease.”

The FDA granted marketing approval in December 1999 for bexarotene capsules in the treatment of cutaneous manifestations of early- and advanced-stage CTCL in patients who were refractory to at least one prior systemic therapy. Ontak (denileukin diftitox), the first in a new class of agents known as fusion proteins, was approved by the FDA in February 1999 for the treatment of patients with persistent or recurrent CTCL whose malignant cells express the CD25 component of the interleukin-2 receptor.

“With Targretin capsules and Ontak, the introduction of Targretin gel allows us to offer patients and physicians a comprehensive range of therapeutic options for all stages of CTCL,” said Dr. Reich.