By Mary Welch
Ligand Pharmaceuticals Inc. received an approvable letter from the FDA for Panretin (alitretinoin) gel as a treatment for AIDS-related Kaposi's sarcoma, and the company expects marketing approval by the end of the year.
"This is not a tremendously major drug, period," said Stefan Loren, an analyst with Legg Mason Wood Walker Inc., in Baltimore. "It has advantages. It's a topical therapy, but it doesn't treat the systemic problem, as other [current therapies] do."
Whatever Panretin's economic benefits, the product proves that Ligand "can take a drug from inception to market," Loren said. "[The company] can play the drug game. As other drugs come to market, the sales force will be in place and will be well-positioned to sell other drugs. That's the principal importance of this," he told BioWorld Today.
Panretin received FDA priority review status, which meant the agency would act on the new drug application (NDA) within six months of May 27, when San Diego-based Ligand submitted it.
The FDA approvable letter follows an 8-1 vote by the Oncologic Drugs Advisory Committee earlier this month. As part of its application, Ligand submitted data from two Phase III trials, one conducted in North America, and the other internationally. The latter trial was stopped at 82 patients in August 1997, when a planned interim analysis showed a 42 percent response rate with Panretin gel, compared with a 7 percent response rate to the placebo. The North American study included 268 patients, half of whom took Panretin, the other half a placebo. After a 12-week blinded period, 35 percent of the Panretin patients showed a response, versus 18 percent of the control group.
Endpoints in both studies were defined using AIDS Clinical Group Criteria, which measure height and size of the Kaposi's lesions.
Side effects included redness, rash, and pain, which could be managed by a reduction in the number of times the drug was applied each day or by temporarily discontinuing the treatment, Ligand officials noted in the NDA. (See BioWorld Today, Nov. 17, 1998, p. 1.)
"There is a high degree of irritation," Loren said. "It's hard to detect exactly the degree, but relief probably would come if you stopped taking it. I don't see it as a huge seller at the present time. It's not a one-stop drug and, if there really is a problem with irritation, I can't see people putting it on their entire body. It could be used as a combination therapy, which would be interesting. It hasn't been studied."
The company expects Panretin gel, the topical formulation of 9-cis retinoic acid, to reach $35 million to $70 million in annual sales. Loren doubted those figures. "But, if peak sales reach $25 million, that still winds up being 50 cents per share," he said. "That's not trivial."
Kaposi's sarcoma, first described in 1872 by Austro-Hungarian dermatologist Moritz Kaposi, was rare until the AIDS epidemic. It is characterized by skin lesions, and may involve oral mucosa, lymph nodes, lungs and gastrointestinal tract. Current therapies include chemotherapy and cryotherapy.
Panretin gel drug was developed in a joint venture with Allergan Inc., of Irvine, Calif., called Allergan Ligand Retinoid Therapeutics (ALRT). In November 1997, Ligand bought ALRT from Allergan for $71.2 million and retained the rights to Panretin. However, Ligand agreed to pay Allergan 15 percent of North American sales revenues from topical Panretin and 10 percent of the international sales revenues. (See BioWorld Today, Nov. 25, 1991, p. 1, and Sept. 26, 1997, p. 1.)
Ligand's stock (NASDAQ:LGND) closed Tuesday at $10.125, up $0.187. *