BioWorld International Correspondent

Basilea Pharmaceutica Ltd.'s lead molecule, an oral treatment for patients with chronic hand dermatitis refractory to topical therapy, attained its primary endpoint in a Phase II trial.

In a double-blind, placebo-controlled, randomized, dose-finding study, 53 percent of patients in the highest dosage group were rated as clear or almost clear after 12 weeks of treatment with the compound, BAL4079. The equivalent statistic for those in the placebo group was 27 percent.

Planning for a Phase III clinical trial is under way. "We would hope to start that this year," Chief Development Officer Anthony Man told BioWorld International. Basel, Switzerland-based F. Hoffmann-La Roche Ltd., which spun out Basilea, also of Basel, in 2000, has an option to license the product at this stage. Basilea is engaged in discussions with it and with other prospective partners, Man said.

The multicenter European Phase II study involved 319 patients who received either placebo or 10, 20 or 40 mg of BAL4079. The 10-mg and 20-mg dosage groups had response rates of 37 percent and 41 percent, respectively. The primary efficacy endpoint was defined by the physician global assessment, a static severity assessment scale, while the main secondary endpoints were patient global assessment and total lesion symptom score, both of which also were attained.

Follow-up is ongoing, Man said. In a previously published Phase II study conducted by an academic group, which was not placebo controlled, there was a wide variation in patient relapse. Some went for more than one year without recurrence, whereas symptoms reappeared in others within six to eight weeks.

"It's quite a heterogeneous condition. The common factor is that all the patients have not had a satisfactory response to topical therapy," Man said. Current treatment is based on the use of hydrating emollients and escalating doses of steroids to control the inflammatory aspects of the condition.

BAL4079 (alitretinoin; 9-cis retinoic acid) is a vitamin A derivative, similar to other natural and synthetic retinoids. It binds to and activates retinoid receptors, which then trigger expression of genes involved in a diverse range of physiological activities, including cell proliferation and differentiation.

Retinoids, Man said, have a long history of application in cancer and in skin disease therapy. "This molecule had been tested in an advanced cancer setting by Roche a number of years ago, but that indication was not pursued," Man said. It is the active ingredient in Panretin gel, marketed as a treatment for skin lesions in AIDS-related Kaposi's sarcoma by Ligand Pharmaceuticals Inc., of San Diego. Basilea, he said, has patent protection covering its use in chronic hand dermatitis.