Panretin(TM) Capsules Show Activity Against Kaposi's Sarcoma
PR Newswire - May 18, 1998 17:30
LGND %MTC V%PRN P%PRN
------------------------------------------------------------------------
Additional Phase II data from AIDS Malignancy Consortium study presented today at ASCO
LOS ANGELES, May 18 /PRNewswire/ -- Final data from a Phase II study of Ligand (LYE-gand) Pharmaceuticals Incorporated (Nasdaq: LGND) Panretin(TM) capsules (alitretinoin) for patients with AIDS-related Kaposi's sarcoma (KS) resulted in an overall response rate of 37 percent (23 of 62 patients), including two patients with complete response, investigators from the AIDS Malignancy Consortium (AMC) reported today at the 34th Annual American Society of Clinical Oncologists (ASCO) meeting in Los Angeles. The study was conducted under the sponsorship of the National Cancer Institute (NCI).
The final analysis of 66 enrolled patients showed that 74 percent were white males; the median age was 38 years; and median CD4+ count was 195. The majority -- 88 percent -- were receiving at least three antiretroviral agents when the study began, including 56 percent (47 of 66 patients) who were receiving protease inhibitors. Seventy-one percent of the patients had received prior therapy for KS, including 29 patients who had local treatment and 45 patients who had received systemic chemotherapy or immunotherapy.
Despite three- and four-drug antiretroviral regimes, the majority of patients had high levels of detectable HIV RNA. There was no difference in response rate in those patients who had detectable viral RNA and those who did not. Only two patients had greater than a one log decline in viral RNA at any time during the study. "These results clearly demonstrate that the effect of Panretin is not linked to an anti-HIV effect, and that the observed responses were not due to antiretroviral therapy," said Dr. Steven Miles, M.D., Associate Professor, UCLA C.A.R.E Center, Division of Hematology-Oncology, UCLA School of Medicine, and a lead investigator of the AMC trial.
"There is clearly a need for an oral therapy for KS which is safe and effective, and Panretin capsules appear to offer patients a treatment option which is an improvement over existing therapies which must be delivered intravenously," added Dr. Miles.
In the study, Panretin(TM) capsules (alitretinoin) were administered once daily at doses increasing from 60 mg/m2/day to 100 mg/m2/day. Study participants had to have biopsy proven KS associated with AIDS and at least five to six skin lesions that were assessed as indicator lesions every two weeks for response. Response was determined by applying the standard AIDS Clinical Trials Group (ACTG) criteria for complete and partial response based on the indicator lesions. The protocol-defined evaluation period was 16 weeks.
Final results from a second Phase II trial of Panretin capsules in AIDS- related KS sponsored by Ligand and announced last month at the National Institutes of Health - AIDS Malignancy Conference, also showed a response rate of 37 percent. Ligand plans to complete development and to file an NDA for Panretin capsules in AIDS-related KS in 1999. This is in addition to the NDA for Panretin(TM) gel (alitretinoin) 0.1% in AIDS-related KS to be submitted shortly.
Kaposi's sarcoma is the most frequent AIDS-related malignancy and is often characterized by multifocal, widespread lesions at the onset of illness. KS may involve the skin, oral mucosa, lymph nodes and visceral organs, such as the lung and gastrointestinal tract. KS was first described in 1872 by the Austro-Hungarian dermatologist, Moritz Kaposi. Until the HIV disease epidemic identified with AIDS, KS remained a rarely diagnosed tumor.
In addition to the AMC and Ligand Phase II trials in KS, Panretin capsules are in an NCI-sponsored Phase I trial in combination with interferon for patients with AIDS-related KS. Two pivotal Phase III trials of Panretin(TM) gel (alitretinoin) 0.1% in patients with AIDS-related KS, which were designed to support an upcoming NDA submission, have been completed. The international Phase III pivotal trial was stopped early because an interim analysis specified in the protocol of the first 82 patients enrolled showed a 42 percent (15 of 36 patients) response to Panretin gel compared with 7 percent (3 of 46 patients) response to placebo (vehicle gel with no active ingredients). Results on the final data set of all 134 patients enrolled were released in February and showed an overall response rate of 37 percent for Panretin gel versus 7 percent for vehicle gel. In the North American Phase III trial, 35 percent of patients treated topically with Panretin(TM) gel (alitretinoin) 0.1% experienced a clinical complete or partial response compared to 18 percent of patients using a placebo (vehicle gel with no active ingredients).
Phase II trials with Panretin(TM) capsules (alitretinoin) are ongoing in breast, prostate and pediatric cancers, and bronchial metaplasia. A Phase II trial in myelodysplastic syndrome and a Phase II study in severe plaque psoriasis have been completed. Ligand expects to be able to determine additional indications for NDA filings from these studies based on results expected to be announced in 1998. Panretin capsules will continue to be studied in patients with acute promyelocytic leukemia (APL).
Since 1989, Ligand Pharmaceuticals Incorporated has established a leadership position in gene transcription technology, particularly intracellular receptor (IR) technology and Signal Transducers and Activators of Transcription (STATs). Ligand has applied IR and STATs technology to the discovery and development of small molecule drugs to enhance therapeutic and safety profiles and to address unmet patient needs in cancer, women's and men's health and skin diseases, as well as osteoporosis, metabolic, cardiovascular and inflammatory disease.
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 Panretin(TM), or any product in the Ligand pipeline, will be successfully developed, that additional proposed indications will have results in subsequent clinical trials supportive of regulatory filings, that regulatory filings will be made on a timely basis, or at all, 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. Ligand undertakes no obligation to update the statements contained in this press release after the date hereof.
SOURCE Ligand Pharmaceuticals Incorporated
/CONTACT: Investors: Susan Atkins, 619-550-7687 or Media: Mary Kenny,
619-550-7536, both of Ligand Pharmaceuticals Incorporated/
/Company News On-Call: prnewswire.com or fax, 800-758-5804,
ext. 509313/
(LGND) |
