European CPMP Recommends Approval for Ligand's Panretin Gel; First Product for Ligand Europe

Business Wire, July 17, 2000

Business Editors/Health & Medical Writers

BIOWIRE2K

SAN DIEGO--(BW HealthWire)--July 17, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) announced today that the Committee for Proprietary Medicinal Products (CPMP) adopted a positive opinion recommending the grant of a Marketing Authorization for Panretin(R) gel (alitretinoin) 0.1% for the topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma (KS). If granted final Marketing Authorization by the European Commission (EC), Panretin gel will be the first approved topical therapy in Europe for KS, the most common AIDS-related malignancy.

"We are pleased with the CPMP's positive recommendation for the approval of the Marketing Authorization Application (MAA) for Panretin gel, the first of our European marketing submissions for four products which have now been approved in the US," said David E. Robinson, Ligand's Chairman, President and CEO. "We view Panretin gel as the first, though not the largest, building block of our European revenue stream. We expect to market this product directly in some countries, with existing partners Ferrer and Alfa Wassermann, and with additional new partners in other markets in Europe."

Ligand submitted its MAA to the European Agency for the Evaluation of Medicinal Products (EMEA) in February 1999. The recommendation of the CPMP serves as the basis for approval by the EC, which would result in one single Marketing Authorization valid in all 15 Member States of the European Union. Typically, final EC approval is issued within three to four months of a positive CPMP opinion.

Ligand has agreements with Ferrer Internacional, S.A., to exclusively market and distribute Panretin gel in Spain, Portugal, Greece, and Central and South America and with Alfa Wassermann to exclusively market and distribute Panretin gel in Italy.

Basis for CPMP Recommendation

The MAA for Panretin gel was based on two multi-center, randomized, double-blind, vehicle-controlled, parallel group Phase III clinical trials, one conducted internationally at 17 sites in Europe, Australia and the U.S. and one conducted at 35 sites in North America. The patient response rate was evaluated using the AIDS Clinical Trials Group (ACTG) criteria for lesion response in KS. The overall response in the international study was 37 percent (clinical complete or partial response) for Panretin gel and 7 percent for the vehicle control group. Results of the North American trial demonstrated that 35 percent of patients treated with Panretin gel experienced complete or partial response compared to 18 percent of patients applying the vehicle gel. Both studies demonstrated statistically significant (p[LESS THAN]0.002) superiority of Panretin gel compared to vehicle gel. Panretin gel was generally well tolerated, and the most common side effects, primarily mild to moderate, occurred almost exclusively at the site of application; side effects included, in most patients, erythema (redness) or skin irritation and, in some patients, pain, skin disorders, itching, flaking and stinging.

"If approved by the EC, Panretin gel will be the first specialist-prescribed, patient-applied treatment for AIDS-related KS in Europe, offering patients and physicians a non-invasive treatment option when currently available therapies have failed or are not appropriate," said Timothy Allington, President of Ligand's European Operations. "We will be working closely with the EMEA, the National Regulatory and Reimbursement authorities and our marketing partners to make this product available to patients in Europe as quickly as possible."

Panretin gel and Kaposi's Sarcoma

Panretin gel received U.S. Food and Drug Administration (FDA) approval in February 1999 for the topical treatment of cutaneous lesions in patients with AIDS-related KS. Ligand currently markets Panretin gel through its specialty oncology and dermatology sales force in the U.S. KS is the most common AIDS-related malignancy and is usually characterized by multi-focal, widespread lesions at the onset of illness. The disease may involve the skin, mouth, lymph nodes and visceral organs, such as the lung and gastrointestinal tract. Ligand estimates that KS affects 10,000 to 20,000 people in North America and Western Europe.

Ligand Pharmaceuticals Incorporated

Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, skin diseases, and men's and women's hormone-related diseases, as well as osteoporosis, metabolic disorders and cardiovascular and inflammatory diseases. Ligand has four drugs approved for marketing in the U.S. -- Targretin(R) (bexarotene) capsules, Targretin(R) gel, ONTAK(R) (denileukin diftitox) and Panretin(R) (alitretinoin) gel -- that are being marketed through its specialty cancer and dermatology sales force. Morphelan(TM), licensed from Elan, is currently under review by the FDA for marketing approval in the U.S. In Europe, a Marketing Authorization Application for Targretin capsules for the treatment of cutaneous T-cell lymphoma is currently under review. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IR) and Signal Transducers and Activators of Transcription (STATs).