Ligand's Panretin Gel Safety and Effectiveness for Treatment of Patients with Cutaneous Kaposi's Sarcoma Presented in Latest JAIDS Publication
SAN DIEGO--(BW HealthWire)--Dec. 14, 1999--
-- November/December 1999 Edition --
Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced today the publication of an article in the Journal of Acquired Immune Deficiency Syndromes (JAIDS) November/December 1999 issue detailing the results of a Ligand-sponsored randomized, controlled, Phase III clinical trial of 0.1% Panretin(R) gel (alitretinoin) for the topical treatment of cutaneous lesions of patients with AIDS-related Kaposi's sarcoma (KS). The article, first authored by Sharon Walmsley, M.Sc., M.D., of the Toronto Hospital in Toronto, Ontario, Canada, concludes that Panretin gel is effective in the topical treatment of AIDS-related Kaposi's sarcoma (KS), noting that researchers observed 35% of patients treated with the drug in the 12-week blinded phase of the study had at least 50% improvement in their cutaneous lesions.
Dr. Walmsley stated, "Panretin gel, in the largest randomized, blinded, vehicle-controlled study conducted with a topical agent in AIDS-related Kaposi's sarcoma, demonstrated statistically significant and clinically meaningful efficacy with an easily manageable safety profile. Treatment with Panretin gel led to at least 50% improvement of the cutaneous lesions in half of the patients during the entire course of the blinded and unblinded phases of study. The effect of the drug was seen in patients who had been previously treated and in those who were on highly active antiretroviral therapy (HAART). Panretin gel is not meant to treat systemic disease, but for those patients with cutaneous manifestations, the drug is a safe and effective treatment that can be applied by patients at home without needing to visit a health care provider."
Clinical Trial Design and Results
A total of 268 HIV infected patients participated in a 12-week, multicenter (in the U.S. and Canada), randomized, double-blind, vehicle-controlled, safety and efficacy Phase III evaluation of Panretin gel applied to cutaneous KS lesions. Patients were to be treated topically three times a day to begin, escalating to four times daily as tolerated, with either Panretin gel or a matching vehicle gel for a minimum of 12 weeks, followed by an open-label phase for patients who elected to continue with Panretin gel or to commence Panretin gel treatment if they had received vehicle gel.
The primary efficacy endpoint was the patient's KS tumor response rate, as determined by evaluation of six index lesions representative of the patient's overall KS cutaneous disease, using AIDS Clinical Trials Group (ACTG) response criteria applied to topical therapy. Patients were also to complete a quality of life questionnaire regarding their satisfaction with the treatment.
In total, 268 patients (134 per group) were assigned randomly to receive initial treatment with either Panretin gel or placebo. Of the 134 patients entered in the 12-week blinded treatment phase of the study and treated with Panretin gel, 47 (35%) had an objective, positive response (at least 50% improvement), compared with 24 (18%) of the 134 patients treated with vehicle gel (p = 0.002, Fisher's exact test). Of 184 patients receiving open-label Panretin gel treatment following the 12-week blinded phase of the trial, 90 patients (49%), including 2 patients who achieved a clinical complete response, met criteria for a positive response. Positive responses to Panretin gel were seen in previously untreated patients and in patients previously treated with systemic and/or topical KS therapy. Patient self-assessment of satisfaction with the drug effect on all treated lesions significantly favored Panretin gel.
During the clinical trial, responses were seen as early as two weeks; however, most responding patients required four to eight weeks of treatment, and some patients did not experience significant improvement until 14 or more weeks of treatment. For patients initially assigned to blinded treatment with Panretin gel and continuing the treatment, the Kaplan-Meier analysis projected a 75% response rate for patients still on treatment at 191 days (27 weeks). Thus, the 35% response rate (47 of 134 patients) limited by the initial 12-week (84 days) blinded phase of the study underestimated the treatment response with Panretin gel, which is projected to be substantially higher with longer duration of treatment. Panretin gel was superior to vehicle gel regardless of the number of concurrent antiretroviral therapies, and side effects include rash, pain, pruritus, erythema, and edema.
Most adverse events were mild to moderate in severity, limited to the application site and reversible upon reduction in application frequency or suspension of application. Relatively few patients (7%) discontinued using Panretin gel due to drug-related adverse events. The results of this study show that Panretin gel is safe and generally well tolerated.
Published today in the Journal of Acquired Immune Deficiency Syndromes (JAIDS) November/December 1999 issue, the article was titled "Treatment of AIDS-Related Cutaneous Kaposi's Sarcoma with Topical Alitretinoin (9-cis-Retinoic Acid) Gel." Authors of the article were Sharon Walmsley, M.Sc., M.D. of the Toronto Hospital in Toronto, Ontario, Canada; Donald W. Northfelt, University of California, San Diego, CA; Barbara Melosky, B.C. Cancer Clinic, Vancouver, British Columbia, Canada; Marcus Conant, Conant Medical Group, San Francisco, CA; Alvin E. Friedman-Kien, Department of Dermatology, Skin and Cancer Unit, New York University Medical Center, New York, NY; Bridget Wagner, ViRx Inc., San Francisco, CA; and the Panretin Gel North American Study Group.
Kaposi's Sarcoma and Panretin Gel
KS is the most frequent malignancy seen in AIDS patients, is often characterized by multi-focal, widespread lesions at the onset of illness, and may involve the skin, oral mucosa, lymph nodes and visceral organs, such as the lung and gastrointestinal tract. The Company estimates that between 20,000 and 35,000 patients in the U.S. and Western Europe, where Ligand intends to be the primary marketer for Panretin gel, are affected by the disease.
In February 1999, Panretin gel was approved by the Food and Drug Administration for the treatment of lesions of patients with AIDS-related Kaposi's sarcoma when systemic therapy is not required. In June 1999, Ligand received approval in Canada to market Panretin gel, which will be marketed and sold through Ligand's wholly owned Canadian subsidiary. Ligand is currently awaiting a response from the European Medicines Evaluation Agency on the Panretin gel Marketing Authorization Application submitted in February 1999.
Alitretinoin, the active ingredient in Panretin gel, is a small-molecule, non-peptide hormone isolated and characterized by Ligand in collaboration with scientists at The Salk Institute and Baylor College of Medicine. Also known as 9-cis-retinoic acid, a derivative of vitamin A, alitretinoin is one of the body's natural regulatory hormones and has a broad range of biological actions influencing cell growth, differentiation, and apoptosis (programmed cell death), among other activities. The discovery of 9-cis-retinoic acid represented the first non-peptide hormone discovery in more than 25 years. Clinical trials using Panretin gel for the treatment of persons with AIDS-related KS were initiated in 1994.
Journal of Acquired Immune Deficiency Syndromes
The Journal of Acquired Immune Deficiency Syndromes is an interdisciplinary journal co-edited by the foremost leaders in clinical virology, molecular biology, and epidemiology. It provides a synthesis of information on AIDS and human retrovirology from all relevant clinical and basic sciences. Under the guidance of an eminent international editorial board, this groundbreaking journal brings together rigorously peer-reviewed original articles, reviews of current research, results of clinical trials, well-documented case reports, and discussions of national policy issues.
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's first two drugs
-- Panretin(R) gel and ONTAK(R) -- were approved for marketing in the U.S. in early 1999 and are being marketed through its specialty cancer and HIV-center sales force in the U.S. Four additional oncology-related products are in late-stage development, including Targretin(R) capsules, Targretin(R) gel, Panretin(R) capsules, and Morphelan(TM) (licensed from Elan). 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).
Except for the historical information contained herein, this news release may contain certain forward looking statements by Ligand 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 that results shown in clinical trials will be repeated in patient population, that any development candidate or any compound or product in the Ligand pipeline will be successfully developed, that any regulatory filings will be made, that any regulatory approvals will be granted in a timely manner, or at all, that if approved any product will be accepted by patients, or that any products will be commercially successful. Additional information concerning these and other factors affecting Ligand's business can be found in press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available via our web site at ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.
Note: Panretin(R) and Targretin(R) are registered trademarks of Ligand Pharmaceuticals Incorporated, and ONTAK(R) is a registered trademark of Seragen, Inc., a wholly owned subsidiary of Ligand. Full prescribing information for Panretin gel may be obtained from Ligand Professional Services by calling toll-free 1-800-964-5836.
Requests for reprints of the article should be directed to Sharon Walmsley, Toronto Hospital, EG219--200 Elizabeth Street, Department of Medicine, Division of Infectious Diseases, Toronto, Ontario, M5G 2C4 Canada; e-mail: sharon.walmsley@uhn.on.ca
Ligand Pharmaceuticals' releases are available on the World Wide Web at www.businesswire.com/cnn/lgnd.htm.
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CONTACT:
Ligand Pharmaceuticals Incorporated
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