FDA grants marketing approval for VALCHLOR gel for treatment of early stage CTCL

Ceptaris Therapeutics, Inc., a privately held, specialty pharmaceutical company, announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for the orphan drug VALCHLOR™ (mechlorethamine) gel 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. VALCHLOR is the first and only FDA-approved topical formulation of mechlorethamine, commonly known as nitrogen mustard. VALCHLOR is a gel that is applied topically once a day and dries on the skin.

“This is good news for patients and the treatment community”

"This is good news for patients and the treatment community," said Youn H. Kim, M.D., 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 a 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 (CTCL) who have received prior skin-directed therapy."

Mechlorethamine is a chemotherapeutic agent previously approved 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 by the National Comprehensive Cancer Network (NCCN). Prior to the approval of VALCHLOR, there were no FDA-approved topical mechlorethamine products; only non-standardized, pharmacy-compounded petroleum ointment or aqueous-based topical preparations were available. Information about pharmacy-compounded preparations is not required to be submitted to or reviewed by FDA prior to their use by patients. Therefore, such preparations do not undergo the same rigorous FDA review as FDA-approved products.

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

"The use of topical mechlorethamine has been documented over several decades, but this is the first time that a product has gone through the rigorous FDA approval process," said Stuart R. Lessin, M.D., former Director of Dermatology at the Fox Chase Cancer Center, President of the Board of Directors of the Cutaneous Lymphoma Foundation and lead investigator in the VALCHLOR pivotal trial. "Not only is VALCHLOR manufactured under FDA's good manufacturing practices, but it will also be accompanied by patient support and assistance programs which are not currently available with compounded mechlorethamine."

Results of the VALCHLOR Pivotal Trial

The approval of VALCHLOR was based on a randomized, observer-blinded, non-inferiority pivotal trial comparing VALCHLOR to a pharmacy-compounded mechlorethamine preparation in patients with stage IA-IIA MF-type CTCL. Patients had received at least one prior skin-directed therapy. Qualifying prior therapies included topical corticosteroids, phototherapy, Targretin® gel, and topical nitrogen mustard (mechlorethamine). Patients were not required to be refractory to or intolerant of prior therapies. In the thirteen center study, 260 patients (the vast majority of whom were IA and IB) were enrolled (1:1 randomization), making it the largest randomized study ever conducted in mycosis fungoides-type CTCL. Results of the study were published earlier this year in JAMA Dermatology.

In the study, 60% of patients treated with VALCHLOR 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 VALCHLOR treatment.