FDA Approves Mechlorethamine Gel for Cutaneous T-Cell Lymphoma

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Ceptaris Therapeutics, Inc, recently announced that the U.S. Food and Drug Administration (FDA) has granted marketing approval for the orphan drug mechlorethamine gel (Valchlor) for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) in patients who have received prior skin-directed therapy. This gel is the first and only FDA-approved topical formulation of mechlorethamine, which is commonly known as nitrogen mustard. The gel is applied topically once a day and dries on the skin.

Mechlorethamine was approved previously for intravenous treatment of mycosis fungoides, the most common type of CTCL. Topical mechlorethamine preparations are currently recommended for the treatment of early-stage CTCL. Prior to approval of the gel, there were no FDA-approved topical mechlorethamine products; only nonstandardized, pharmacy-compounded petroleum ointment or aqueous-based topical preparations were available.

The availability of the FDA-approved mechlorethamine gel will allow physicians to use this FDA-approved version of topical mechlorethamine to treat patients with stage IA and IB mycosis fungoides-type CTCL who have received prior skin-directed therapy. In addition to consistent, controlled manufacturing processes, the gel will be provided with labeling, which includes data and instructions for proper use to help achieve the best possible clinical results.

Pivotal Trial

The approval of mechlorethamine gel was based on a randomized, observer-blinded, noninferiority pivotal trial comparing the gel to a pharmacy-compounded mechlorethamine preparation in patients with stage IA–IIA mycosis fungoides–type CTCL. Patients had received at least one prior skin-directed therapy. Qualifying prior therapies included topical corticosteroids, phototherapy, bexarotene gel (Targretin), and topical nitrogen mustard (mechlorethamine). Patients were not required to be refractory to or intolerant of prior therapies.

In the 13-center study, 260 patients were enrolled in a 1:1 randomization. The vast majority of patients were stage IA and IB. Results of the study were published earlier this year in JAMA Dermatology.

In the study, 60% of patients treated with mechlorethamine gel had a confirmed response at 12 months, defined as reduction of at least 50% in the Composite Assessment of Index Lesion Severity (CAILS) score, while 48% of those treated with the compounded control achieved a confirmed response. Complete responses constituted a minority of the CAILS overall response. CAILS responses were seen as early as 1 month, with further responses observed through 11 months of treatment. No systemic absorption of mechlorethamine was detected with mechlorethamine gel treatment.

‘Good News’ for CTCL Treatment

“This is good news for patients and the treatment community,” said Youn H. Kim, MD, Joanne and Peter Haas Jr. Professor for Cutaneous Lymphoma Research, Professor of Dermatology, and Director, Multidisciplinary Cutaneous Lymphoma Clinic, Stanford University School of Medicine. “We now have the confidence of an FDA-approved product backed by evidence from a well-controlled clinical trial that demonstrated clinically meaningful responses in the majority of patients with stage IA and IB mycosis fungoides–type cutaneous T-cell lymphoma who have received prior skin-directed therapy,” Dr. Kim said. ■