Valchlor (mechlorethamine) gel 0.016% is applied topically once a day to affected areas of the skin. Valchlor is the first and only FDA-approved topical formulation of mechlorethamine.
In the US, Valchlor gel 0.016% is indicated for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in patients who have received prior skin-directed therapy.
Valchlor is commercially available in the US (since 2013) and in Israel through special import authorization procedure (since 2016). In France, patients benefit from the drug under a temporary authorization for use ("ATU") program initiated during the second half of 2014.
In March 2017, the European Commission granted marketing authorization for the use of the active ingredient of Valchlor under the brand name Ledaga® (chlormethine gel) 160 micrograms/g for the treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL). Subject to fulfilling the agreed commitments and achieving market access in various countries, a potential first European launch of Ledaga is not expected before H1 2018.
The efficacy of Valchlor was assessed in a randomized, multicenter, observer-blind, non-inferiority trial of 260 patients. Patients were stratified based on Stage (IA vs IB and IIA) and then randomized to receive Valchlor gel 0.016% w/w of mechlorethamine (equivalent to 0.02% mechlorethamine HCl) or Aquaphor®-based mechlorethamine HCl 0.02% ointment (compounded mechlorethamine). Patients had received at least one prior skin-directed therapy. Qualifying prior therapies included topical corticosteroids, phototherapy, Targretin® gel, and topical nitrogen mustard. Patients were not required to be refractory to or intolerant of prior therapies. Treatments were applied topically on a daily basis for 12 months.
60% of the patients on the Valchlor arm and 48% of patients on the comparator arm achieved a response based on the Composite Assessment of Index Lesion Severity (CAILS) score. Valchlor was non-inferior to the comparator based on a CAILS overall response rate ratio of 1.24 (95% CI 0.98, 1.58). Complete responses constituted a minority of the CAILS or Severity Weighted Assessment Tool (SWAT) overall responses. The onset of CAILS overall response for both treatment arms showed a wide range from 1 to 11 months.
The most common adverse reactions (≥5%) were dermatitis (56%), pruritus (20%), bacterial skin infection (11%), skin ulceration or blistering (6%), and skin hyperpigmentation (5%). These reactions may be moderately severe or severe. Elderly patients aged 65 and older may be more susceptible. Depending on severity, treatment reduction, suspension, or discontinuation may be required.
Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, et al. Topical chemotherapy in cutaneous T-cell lymphoma: Positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013;149(1):25-32.