PR Newswire, 810 Seventh Avenue, New York, NY 10019 - Tuesday 26 August 1997.

"The protocol had a provision that permitted early stopping of the trial prior to full patient enrollment if the treatment with Panretin Topical Gel was clearly beneficial to patients," according to Marvin E. Rosenthale, Ph.D., President of Allergan Ligand Retinoid Therapeutics, Inc. (ALRT) (Nasdaq: ALRI).

"These positive interim results are the first confirmation of those obtained in earlier Phase I/II studies," according to John R. Gibson, Ph.D., Allergan Senior Vice President of Development.

This international trial, conducted by Allergan, Inc. (NYSE: AGN) in Europe, Australia and the United States, is the second of two Phase III pivotal trials of Panretin(TM) Topical Gel in KS patients, which have been launched under a U.S. Investigational New Drug (IND) application on behalf of ALRT. Patient accrual is now complete for a North American Phase, III pivotal trial of similar design conducted by Ligand Pharmaceuticals Inc., (Nasdaq: LGND). The results of this trial are expected in the fourth quarter of 1997.

ALRT expects that both Phase III trials could be used in the filing of a U.S. New Drug Application (NDA) later this year or early next year, though the international Phase III trial was not originally scheduled to be part of the U.S. NDA. Panretin Topical Gel would be the first topical product to be submitted to the FDA in this disease.

Study Design

Both Phase III trials are randomized, double-blind, placebo-controlled 12-week studies of topical 9-cis-retinoic acid gel (Panretin(TM)) in the palliative treatment of cutaneous AIDS-related KS. The objectives of the trials are to compare the efficacy of 0.1% Panretin Topical Gel to placebo when applied topically and to determine the safety and tolerability of the formulation in this patient group. Palliative treatment means alleviation of cutaneous lesions, in this case reduction in the size or number of KS lesions on the skin as per AIDS Clinical Trial Group (ACTG) criteria as applied to topical therapy.

Methodology

The protocol for the Phase III trial conducted by Allergan on behalf of ALRT calls for patients to be treated with either a 0.1% gel formulation of Panretin(TM) or placebo vehicle gel, applied twice daily to cutaneous KS lesions for 12 weeks. It was expected that approximately 270 patients would be required to be enrolled based on estimates of a response rate of 25% in the Topical Panretin treatment arm and up to 10% in the placebo arm.

The international trial, conducted at 30 centers, was initiated in September of 1996 and was designed with an interim analysis which would permit its early conclusion if a significant number of patients were receiving clear benefit from Panretin Topical Gel treatment.

The protocol stated:

"If there is a large benefit for the active treatment it will be important to stop the trial early. Therefore one interim analysis will be undertaken. If the results show a clear benefit for the active treatment they may be submitted to European Regulatory Authorities for early Product Registration."

The interim analysis compared the response rates of the two treatment groups statistically to determine if the level of significance ("p value") was 0.005 or less. If that level of significance had not been reached, the trial would have continued to 270 patients as originally planned.

However, the level of significance, "p value" of 0.00027 was reached triggering an early stop as permitted by the protocol.

Results

Of 82 patients with biopsy confirmed KS, 36 received therapy with 0.1% Panretin(TM) Topical Gel and 46 were treated with placebo (vehicle gel with no active drug). Patients were seen for assessment at 2, 4, 8 and 12 weeks after trial entry and responses were defined using ACTG criteria applicable to topical therapy. After 12 weeks, patients could be enrolled in a separate open label protocol and be treated with Panretin Gel for up to nine additional months.

Forty-two percent (42%) of patients treated with Panretin Topical Gel had a complete or partial response as compared with 7% of patients treated with placebo.

Because the required level of significance in response was achieved, ALRT determined that Panretin Gel was active in the trial and new patients should no longer be enrolled. Patients currently enrolled in the Allergan sponsored trial of Panretin Topical Gel will continue with their assigned treatment and, upon completion of the "blinded" phase, be allowed to enroll in the "open label" trial which provides Panretin Topical Gel to all the patients in the trial without comparison to placebo.

In the U.S. Phase III pivotal trial of Panretin Topical Gel in KS sponsored by Ligand, patient accrual is complete and the treatment and follow-up evaluation of 268 patients is ongoing. ALRT does not expect the positive results in the international trial to significantly interfere with the U.S. trial patient follow-up now underway.

"While the results in the Allergan-sponsored international study are quite dramatic, we will continue each patient's assigned treatment in both the Ligand-sponsored and Allergan-sponsored studies through completion of the blinded phase," according to Dr. Rosenthale. "We expect to be able to analyze and announce the final results of the North American Phase III trial early in the fourth quarter of this year, and if the results are positive, to file an NDA within two to three months," Dr. Rosenthale said.

Panretin(TM) Oral Capsules are also being studied in patients with AIDS- related Kaposi's sarcoma. Other studies are ongoing in breast, ovarian and prostate cancer and a study in severe plaque psoriasis has been completed. ALRT expects to be able to determine additional indications for NDA filing from these studies based on results ALRT expects to announce later this year or early in 1998. Oral Panretin is also in Phase III pivotal trials in patients with acute promyelocytic leukemia (APL).

Panretin is a proprietary product of Allergan Ligand Retinoid Therapeutics, Inc., a company whose primary purpose is to discover and develop drugs based on retinoids. Retinoids have a broad range of biological actions, and evidence suggests that retinoids may be useful in the treatment of skin diseases, metabolic diseases, a variety of cancers, including certain forms of leukemia, as well as eye diseases.

This statement may contain certain forward looking statements by ALRT and actual results could differ materially from those described as a result of factors including, but not limited to, the following. There can be no assurance Panretin, or any product in the ALRT pipeline, will be successfully developed, that regulatory approvals will be granted, that patient and physician acceptance of these products will be achieved, that final results of human clinical trials will be consistent with any interim results, or that final results will be supportive of regulatory approvals required to market products. ALRT undertakes no obligation to update the statements contained in this press release after the date hereof.

NOTE TO EDITORS: If you would prefer to receive Ligand's press releases via email, please inform us at investors@ligand.com and request to be placed on our priority email list.

CONTACT: Susan E. Atkins for ALRT, 619-550-7687/

Copyright (c) 1997/PR NewsWire. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, PR Newswire, 810 Seventh Avenue, New York, NY 10019.
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