Company Press Release
SOURCE: Ligand Pharmaceuticals Incorporated
Positive Phase II Data of Panretin(TM) Capsules in Kaposi's Sarcoma Presented at AIDS Malignancy Conference
First Public Presentation of Interim Data Confirmed by Final Analysis
SAN DIEGO, April 7 /PRNewswire/ -- Clinical investigators presented interim and final Phase II data today which showed that Ligand (LYE-gand) Pharmaceuticals Incorporated (Nasdaq: LGND - news) Panretin(TM) Capsules have substantial antitumor activity in patients with AIDS-related Kaposi's sarcoma (KS). The results were presented today at the Second National AIDS Malignancy Conference sponsored by the National Cancer Institute (NCI) in Bethesda, Maryland and showed response rates based on intent-to-treat analysis of 46 percent (12 of 26 patients) at interim and 37 percent (21 of 57 patients) at final analysis. The response rates based upon the protocol-defined evaluable patient data set were 63 percent (12 of 19 patients) at interim analysis and 57 percent (21 of 37 patients) at final analysis. Assuming Phase III data which is supportive, Ligand is working to complete development and to file an NDA for Panretin Capsules in AIDS-related KS in 1999. This is in addition to the Panretin(TM) Gel NDA for AIDS-related KS to be submitted shortly.
This study was conducted by Ligand and is one of two similar multicenter, open-label studies designed to determine the safety and efficacy of Panretin Capsules in patients with AIDS-related KS. The second study was conducted directly by the AIDS Malignancy Consortium (AMC). Preliminary findings from the final data analysis from both studies were announced by Ligand earlier this year.
''With final analysis of the data confirming the response rates from the interim analysis, we can say that Panretin Capsules are improving the condition for many study participants suffering from this devastating disease,'' said lead investigator of the Ligand study, David Aboulafia, M.D., attending hematologist/oncologist at Virginia Mason Medical Center and Medical Director, Bailey-Boushay House in Seattle.
The Study
In a Phase II, multicenter, open-label clinical trial, Panretin(TM) Capsules (9-cis-retinoic acid) were administered orally to HIV-positive patients with biopsy proven Kaposi's sarcoma (KS) in once daily doses of 60 mg/m2/day escalating to 100 mg/m2/day. Five study sites enrolled a total of 57 patients, of whom 26 were available for the intent-to-treat dataset for the interim analysis (received study drug and had at least one set of KS lesion assessments as of the interim date). All patients were men, with a median age of 40 years (range 30 to 59), and median CD4+ count of 176/mm3 (range 2 to 672). The mean number of cutaneous KS lesions was 35 (range 7 to 117).
Responding patients had a median CD4+ count of 170 (range 4 to 349); baseline CD4+ counts did not appear to be predictive of response. Nearly all patients (98 percent) were on highly active antiretroviral therapy, including at least one protease inhibitor (86 percent) prior to the start of Panretin Capsules therapy and there was no statistical association between antiretroviral therapy and response.
The most frequent related side effects, which were generally mild to moderate, included headache (70 percent), dry skin (51 percent), redness (47 percent), alopecia (42 percent), peeling (33 percent) and itching (21 percent). Two patients developed pancreatitis; one patient fully recovered and the other subsequently died of an unrelated, disseminated fungal infection.
Results and Conclusion
The overall response rate at the interim analysis determined by applying AIDS Clinical Trial Group criteria to each patient's group of 6 indicator lesions was 46 percent (12 of 26 patients) for the intent-to-treat dataset, and 63 percent (12 of 19 patients) for the protocol-defined evaluable patient dataset. The median time to response was 6.9 weeks (range 2.3 to 21.1) and the median duration of response was 16.6+ weeks (range 6.3+ to 33.9) with all but one responding patients continuing on treatment.
The final analysis of the interim study suggests that Panretin Capsules have substantial anti-tumor activity in AIDS-related KS with a manageable safety profile. The final data will include information on all 57 study participants. A preliminary analysis of the final data showed no statistical difference from response rates in the interim analysis.
When only protocol-defined evaluable patients were evaluated, the response rates were 63 percent (12 of 19 patients) at the interim and 57 percent (21 of 37 patients) at the final analysis.
Kaposi's sarcoma is the most frequent malignant cancer lesion in patients who are HIV-positive and is often characterized by multifocal, 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. 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.
Panretin(TM) Capsules have completed two single-agent Phase II trials and are in an NCI-sponsored Phase I trial in combination with interferon for patients with AIDS-related Kaposi's sarcoma. Two pivotal Phase III trials of Panretin(TM) Gel in KS have been completed, which were designed to support an NDA filing early in 1998. The international Phase III pivotal trial was stopped early because an interim analysis specified in the protocol 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 134 patients were released last month 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, 35.1 percent of patients treated topically with Panretin(TM) Gel experienced complete or partial response compared to 17.9 percent of patients using a placebo (vehicle gel with no active ingredients).
Phase II trials with Panretin Capsules are ongoing in breast, prostate and pediatric cancers, and bronchial metaplasia. A trial in myelodysplastic syndrome and a 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 Capsules, Panretin Gel, or any product in the Ligand pipeline, will be successfully developed, that final data will be consistent with interim data, that regulatory approvals will be granted in a timely manner, or at all, that patient and physician acceptance of these products will be achieved, 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 |
