Ligand Pharmaceuticals Inc. will begin this fall three open-labelPhase III studies of its retinoid-derived drug, Targretin, for cutaneousT cell lymphoma (CTCL), a disfiguring and potentially fatal cancerthat starts in the skin and spreads throughout the body.
The trials, slated to enroll a total of 180 patients, are expected to becomplete in about a year. Ligand, of San Diego, anticipates filing anew drug application (NDA) with the FDA in the first half of 1998.
Retinoids are naturally occurring hormones chemically related tovitamin A and known to control cellular activities through activationof intracellular receptors.
Targretin, a synthetic compound, is designed to selectively stimulateretinoid X receptors (RXR), which are believed to have a strong linkto cell death, or apoptosis.
Ligand's most advanced retinoid-based compound, Panretin, is asynthetic version of 9-cis-retinoic acid, a retinoid discovered by thecompany's scientists. Panretin binds to RXRs and retinoic acidreceptors (RARs), which are two subfamilies of six intracellularreceptor types involved in controlling cell growth, differentiation andapoptosis.
A topical gel form of Panretin is in Phase III trials for cutaneousKaposi's sarcoma in AIDS patients. The drug is being developed byAllergan Ligand Retinoid Therapeutics Inc., of San Diego, a jointventure between Ligand and Allergan Inc., of Irvine, Calif. Thecompanies expect to file an NDA in the second half of 1997.
In the Targretin studies oral and topical gel forms of the compoundwill be evaluated in three trials each involving 60 patients. One oftwo Phase II/III studies with Targretin oral capsules will enroll CTCLpatients with refractory or persistent early stage disease. Patients withadvanced refractory CTCL will participate in the other Phase II/IIItrial.
The third study _ a Phase III trial _ of topical Targretin also willtarget patients in early stages of CTCL.
Clinical endpoints include reduction of tumors, duration of responseto the drug and time to progression of the disease.
Current treatments for CTCL include photophoresis and vinblastine,an anti-cancer agent. No topical therapy is available.
Targretin also is under evaluation in Phase IIb trials for four othercancers: lung, head and neck, kidney and Kaposi's sarcoma.
Earlier this year, a Phase I/II study of the drug for CTCL showed twoof nine patients taking the oral capsules experienced reduction in skintumors. In another trial of Targretin topical gel, results showed 11 of30 patients receiving the treatment saw clearance of at least 50percent of their tumors.
Ligand's stock (NASDAQ:LGND) closed Thursday at $12.63, up 38cents. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.