By Randall Osborne
Staff Writer
Based on strongly positive data from its second Phase III trial of a topical treatment for AIDS-related Kaposi's sarcoma, Ligand Pharmaceuticals Inc. said it will file a new drug application (NDA) for Panretin with the FDA during the first quarter of next year.
"That's incredibly fast," said Susan Atkins, spokeswoman for San Diego-based Ligand, "but we've been compiling data throughout the trial and doing as much preparation as we could."
About 500 patients have been studied with Panretin Gel, she added. Those evaluated in Phase III trials in North America (268) and internationally (132) join the 115 patients studied in Phase I/II trials, completed last year.
The company hopes for quick approval. "We think it's not unusual to expect a six-month turnaround at the agency," said Atkins. Treatments for AIDS-related conditions often are given special consideration, she noted.
Panretin Gel, the topical formulation of 9-cis retinoic acid, is expected to be the first such drug for Kaposi's sarcoma to reach the FDA for marketing clearance. The disease, first described in 1872 by Austro-Hungarian dermatologist Moritz Kaposi, was rare until the epidemic of AIDS. It is characterized by skin lesions, and may involve oral mucosa, lymph nodes, lungs and gastrointestinal tract.
Currently available therapies for Kaposi's sarcoma include chemotherapy and cryotherapy. Panretin Gel is an alternative that is non-invasive and patient-controlled, with tolerable side effects.
"It shrinks the lesions," Atkins said.
Ligand developed the drug in a joint venture with Allergan Inc., of Irvine, Calif. In August, their company, called Allergan Ligand Retinoid Therapeutics (ALRT), put an early halt to the pivotal Phase III international trial of Panretin. The decision to end the trial, which was conducted by Allergan, was based on highly significant improvement seen in the treated patients as compared with controls. An interim analysis of 82 patients showed a 42 percent response rate among those using Panretin, compared with 7 percent of those given a placebo. (See BioWorld Today, Aug. 28, 1997, p. 1.)
By the conclusion of the international trial — data from which will be included in the FDA filing and used to seek a marketing authorization application in Europe — 132 patients were enrolled.
In November, Ligand bought ALRT from Allergan for $71.2 million. Allergan exercised its option to obtain one-half interest in the assets and technologies of ALRT, which had 2,000 retinoid compounds. Allergan paid $8.9 million to Ligand to take part in a lottery dividing the compounds, but Ligand retained rights to Panretin. (See BioWorld Today, Nov. 25, 1997, p. 1.)
The data from the North American trial show 35 percent of 134 patients using Panretin responded to treatment, compared with 17.9 percent of the same number given a placebo.
Like the international trial, it was a randomized, double-blind, placebo-controlled study lasting 12 weeks, comparing the efficacy of Panretin to placebo and determining the safety and tolerability of the gel when applied to cutaneous lesions two to four times daily.
Responses were defined using AIDS Clinical Trial Group criteria, which measure height, area and color of lesions, examined at two, four, eight and 12 weeks after the study began.
Patients Improved More With Longer Treatment
Patients given Panretin in the North American trial had the option of continuing treatment when the blinded portion of the trial was finished. "For the people who were on Panretin during the blinded trial, the response was 35 percent, but when they stayed on, it went up to almost 50 percent," Atkins said.
Sixty-six patients continued with Panretin, and their response rate, from the blinded phase through the open-label phase, was 49.3 percent. "People who work with retinoids have known all along that they are not the fastest working drugs on the block," Atkins said. "But the responses are very durable."
Patients initially given a placebo were allowed to begin Panretin therapy after the blinded phase. Measurements of baseline lesions were calibrated again before starting the open-label phase. For the 86 who chose Panretin, the response rate was 29 percent.
"That's very impressive," Atkins said. "They were starting fresh."
Ligand has an oral formulation of Panretin in Phase II trials as a single agent, and in a Phase I trial in combination with interferon. Phase II trials of Panretin Oral also are ongoing in breast, ovarian and pediatric cancers, bronchial metaplasia and myclodysplastic syndrome. A study in severe plaque psoriasis has been completed.
Results from these studies, to be available next year, are expected to produce other indications for NDA filings.
Phase III pivotal trials are ongoing for Panretin Oral against acute promyelocytic leukemia, Atkins said, and the drug is on track for an NDA filing in 1999.
Ligand's stock (NASDAQ:ALRI) closed Thursday at $13.438, down $0.438. *