LEDAGA

What it is

Ledaga is a gel containing chlormethine hydrochloride, with each gram of gel containing chlormethine hydrochloride equivalent to 160 micrograms of chlormethine. Chlormethine is a bifunctional alkylating agent that reacts with DNA to form cross-links, inducing the death of rapidly proliferating cells.

Approved indications

— Topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-type CTCL) in adult patients.

Dosing overview

A thin film of Ledaga should be applied once daily to affected areas of the skin. Treatment with Ledaga should be stopped for any grade of skin ulceration or blistering, or moderately severe or severe dermatitis. Upon improvement, treatment with Ledaga can be restarted at a reduced frequency of once every 3 days. If reintroduction of treatment is tolerated for at least 1 week, the frequency of application can be increased to every other day for at least 1 week and then to once-daily application if tolerated. The dosing recommendation for elderly patients (≥65 years old) is the same as for younger adult patients.

Key safety warnings

Contact with mucous membranes, especially those of the eyes, must be avoided. Exposure of mucous membranes such as the oral mucosa or nasal mucosa causes pain, redness, and ulceration, and these may be severe. Exposure of the eyes to chlormethine causes pain, burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior eye injury may occur. Patients should be assessed during treatment for skin reactions such as dermatitis, pruritus, blisters, ulceration, and skin infections. The face, genitalia, anus, and intertriginous skin are at increased risk of skin reactions to topical chlormethine. Therefore, administration of Ledaga in these areas should be avoided. Skin-directed therapies for MF-type CTCL have been associated with secondary skin cancers, although the specific contribution of chlormethine has not been established. Patients should be monitored for development of skin cancers during and after discontinuation of treatment with chlormethine. This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information.

Contraindications

Hypersensitivity to chlormethine or to any of the excipients listed in section 6.1.

PBS listing

Ledaga 160 micrograms (as hydrochloride) per gram, 60 gram tube is listed on the PBS with authority required restriction at an ex-manufacturer price of A$1622.09.

Regulatory history

Ledaga was first registered on the ARTG on 22 June 2021. In March 2023, the PBAC recommended against listing for mycosis fungoides-type cutaneous T-cell lymphoma in adults with MF-type CTCL. In November 2023, the PBAC recommended the medicine for topical treatment in adult patients with no more than 25 percent body surface area involved, cost-minimised to phototherapy with a small price premium for improved accessibility. The TGA identified an unmet medical need for an approved topical treatment for mycosis fungoides-type cutaneous T-cell lymphoma. Ledaga, containing chlormethine hydrochloride, demonstrated significant clinical efficacy for early stage disease, addressing this need despite potential for skin reactions.