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.
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 doctors 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.