Manhattan Pharmaceuticals, Inc. said it has concluded successful pre-IND (Investigational New Drug) meetings with the US Food and Drug Administration (FDA) and may file IND applications for both Altoderm and Altolyn(tm). The company intends to develop Altoderm (topical cromolyn sodium) to treat pruritus (itching) associated with atopic dermatitis, and Altolyn (oral tablet cromolyn sodium) to treat mastocytosis.

The pre-IND meetings were held to obtain the FDA's concurrence regarding the requirements for IND applications, and to clarify development pathways and regulatory status of both products in the US.

Based on a review of the submitted package for Altoderm, including data from the two previously reported phase III clinical studies (conducted in Europe by Thornton & Ross Ltd.), the FDA determined that following completion of certain nonclinical studies and the acceptance of an IND, phase II clinical studies may be initiated in the US. The FDA also concurs that the proposed indication of pruritus associated with dermatologic conditions including atopic dermatitis can be pursued.

Based on a review of the submitted package for Altolyn, the FDA concurred that the 505(b)(2) NDA would be an acceptable approach provided a clinical bridge is established between Altolyn and Gastrocrom, the oral liquid formulation of cromolyn sodium currently approved in the US to treat mastocytosis. The FDA also affirmed that a single, phase III study demonstrating the efficacy of Altolyn over placebo may be sufficient to support a product approval in the US. In addition, the FDA also concurs that no additional nonclinical studies will be required to support an IND application. Manhattan Pharmaceuticals expects to file an IND with a phase III protocol following completion of the required IND enabling tablet development and manufacturing work.

"We are pleased to have confirmed the regulatory and development paths for Altoderm and Altolyn with the FDA," stated Douglas Abel, president and chief executive officer, Manhattan Pharmaceuticals. "The successful completion of these meetings is an important milestone for the company because it provides important clarity for our clinical programMEs here in the US."

Section 505(b)(2) of the US Food, Drug and Cosmetic Act permits the FDA to approve a New Drug Application (NDA) in part on the basis of published literature or on a previous finding of safety or effectiveness of a drug. The process allows the sponsor to use the existing information in the public domain to support their approval. A 505(b)(2) application can apply to new chemical entities or to changes to previously approved drugs. Examples of 505(b)(2) applications include changes to formulation, dosage forms, or routes of administration. This procedure potentially allows for a more rapid approval timeline compared to new chemical/molecular entities based in part by referencing this information, the company said.

Altoderm is a topical formulation of cromolyn sodium, a non-steroidal, anti-allergic medication which is categorized as a mast cell stabilizer. Cromolyn sodium has been shown to block allergic reactions by inhibiting the release of inflammatory mediators, including histamine and leukotrienes. It has been used worldwide for over 35 years to treat a number of allergic conditions including asthma, allergic rhinitis, allergic conjunctivitis, and mastocytosis.

Altolyn is a novel tablet formulation of cromolyn sodium that has been formulated using site specific drug delivery technology. This unique formulation targets release of the drug in the upper region of the small intestine. Since cromolyn sodium is a mast cell stabilizer, treatment with Altolyn may control the symptoms of mastocytosis, as well as other mast cell associated disorders (e.g., food allergies and symptoms of irritable bowel syndrome).