Manhattan Pharmaceuticals To Focus On Dermatology After Obesity Candidate Fails

Firm will discontinue development of oral oleoyl-estrone for obesity after it failed to show a significant difference over placebo in Phase IIa studies.

Manhattan Pharmaceuticals will focus its drug development program on four dermatology candidates after the company announced plans to discontinue development of oral oleoyl-estrone for obesity July 9.

"Going forward, we intend to continue with the advancement of our four clinical stage product candidates and the exploration of additional opportunities in the area of dermatology/immunology, as well as endocrine/metabolic disorders," CEO Douglas Abel said during a conference call July 10.

The company opted to discontinue development of OE after it failed to show a statistically significant effect on weight loss over placebo in two Phase IIa studies. The studies also showed OE resulted in dose-dependent increases in estrone and estradiol and concomitant suppression of testosterone. Although the hormonal changes returned to baseline after treatment was stopped, they preclude studying OE at higher doses, Chief Medical Officer Alan Harris explained.

"These two Phase IIa studies produced very high quality data that provided definitive results," Harris said. "We are able to conclude with complete confidence that Manhattan's program of OE should be discontinued."

New York-based Manhattan Pharmaceuticals had initiated the Phase IIa studies, one in commonly obese patients and one in morbidly obese patients, based on positive preclinical data and an encouraging Phase I clinical profile.

The multi-center, randomized, double-blind, placebo-controlled trials enrolled 100 patients in the common obesity study and 24 patients in the morbid obesity study. Subjects in the common obesity trial were randomized to one of four treatment groups: 5 mg, 10 mg, or 20 mg OE or placebo once daily for two 14-day dosing cycles, each followed by a 28-day treatment-free period. In the morbid obesity study, patients were randomized to receive 10 mg or 30 mg OE or placebo once daily for 30 days.

Decreases in body weight were seen in the 5 mg OE arm in the common obesity study and in the 30 mg OE arm of the morbid obesity study. However, those changes were not statistically significant, Harris reported.

Manhattan's four clinical stage opportunities in dermatology include topical PTH (1-34) for psoriasis, Altoderm for atopic dermatitis and eczema, Altolyn for mastocytosis and Hedrin , a non-insecticidefor head lice. The company acquired the North American development rights to Altoderm (topical cromolyn) and Altolyn (oral cormolyn) from U.K. drug maker Thornton & Ross Limited in April. The firms followed up in June with a third similar licensing arrangement for Hedrin, which is already available in Europe.

Preliminary data from a Phase III trial on Altoderm, already ongoing in Europe, is anticipated in the third quarter.

"Our team at Manhattan Pharmaceuticals is presently preparing to meet with FDA to determine the regulatory pathway for Altoderm in the U.S., Abel said. "It is our expectation that this meeting will take place in the second half."

The exec noted that the firm is also preparing to meet with FDA to determine a path forward for Altolyn and Hedrin. Manhattan believes Altolyn, a novel tablet formulation of cromolyn sodium, may be a candidate for accelerated approval; the firm would file the NDA via the 505(b)(2) pathway.

In addition, the company is seeking to file an IND for PTH (1-34), a parathyroid hormone-related peptide analog, for psoriasis in the third quarter, which could potentially result in the initiation of a Phase IIa clinical trial in the second half of the year.

In line with the firm's strategic focus, Manhattan said it plans to pursue out-licensing opportunities for Propoful Lingual Spray for pre-procedural sedation.

- Jessica Merrill ([email protected])