By Mary Welch

Ligand Pharmaceuticals Inc. popped the champagne bottles a few days early as the FDA approved Targretin capsules for treating all stages of refractory cutaneous T-cell lymphoma (CTCL). It is the third FDA approval for the San Diego-based company this year.

"We're absolutely delighted," said Christiane Sheid, Ligand's vice president of finance and corporate communications. "We had three FDA approvals this year. Targretin gel is under FDA review. We have a productive portfolio and we're advancing our projects with our partners. A very good year."

The approval was for once-daily oral administration for the treatment of cutaneous manifestations of CTCL in patients who are refractory to at least one prior systemic therapy. However, the FDA requested post-approval Phase IV clinical and pharmacokinetic studies.

"The FDA requested the studies and we agreed," she said. "I don't know what the nature of those studies are but one might speculate that it would be the longer-term effects of the drug."

The company expects to launch the product no earlier than mid-January. So far, no pricing points have been set, Sheid said.

Some 16,000 to 20,000 people in the U.S. suffer from CTCL, which is a cancer of T lymphocytes (the white blood cells involved in the body's immune system). The disease generally manifests itself initially in the skin but, over time, it can progress to other organs. Early stage CTCL has a median survival of 10 years while late-stage disease has a median survival of three years. Current treatments are limited and may include electron beam therapy and photophoresis or psoralen plus UV-A light.

"There is no cure but Targretin helps in reducing the effects of the disease," Sheid said. "Patients have super-sensitive skin and patients have reported that they couldn't even sleep because they kept itching. With Targretin the skin moves to a more normal condition. It alleviates the situation."

Targretin (bexarotene) is a synthetic retinoid analogue. Retinoids are naturally occurring hormones chemically related to vitamin A, and are known to regulate a number of cellular activities, including cell growth. They work through six receptors that can be classified into two groups: retinoid acid receptor (RAR) and retinoid X receptor (RXR). Targretin acts through RXR.

The approval is based in part on two Phase II/III multicenter, open-label, historically controlled studies involving 152 patients. The studies showed Targretin, taken at a dose of 300 milligrams per square meter, resulted in at least 50 percent improvement in 48 percent of patients. That cleared the FDA's hurdle requiring that 20 percent of patients show a 50 percent improvement. (See BioWorld Today, June 25, 1999, p.1.)

Targretin also is in Phase II studies for breast cancer and psoriasis.

Although Targretin was discovered by Ligand, it was being developed in a collaboration with Eli Lilly and Co., of Indianapolis. The two companies signed a deal worth up to $190 million in 1997. However, Lilly stopped Targretin's development earlier this year, opting instead to focus on developing with Ligand second-generation RXR products for diabetes. (See BioWorld Today, Feb. 19, 1999, p. 1.)

Ligand also has filed a new drug application for Targretin gel for cutaneous lesions in patients with Stage IA, IB, or IIA cutaneous T-cell lymphoma. If approved, it would be the first topical treatment for patients with CTCL. (See BioWorld Today, Dec. 13, 1999, p. 1.)

In February, the FDA approved two of Ligand's drugs: Ontak, a fusion protein therapy for the treatment of persistent or recurrent CTCL, and Panretin (aliretinoin) gel for Kaposi's sarcoma. Ontak was developed by Seragen Inc., of Hopkinton, Mass., a wholly owned subsidiary of Ligand. (See BioWorld Today, Feb. 8, 1999, p. 1; and Feb. 4, 1999 p. 1.)

Ligand's stock (NASDAQ:LGND) closed Wednesday at $12.75, up $1.625.