Good news for LGND. Initially, it appears there is just an 17% response rate over the placebo (35% vs. 18%), which is statistically significant and with other trials, more than sufficient for FDA approval. However, a closer reading shows that 49.3% of those treated continuously with Panretin responded. It seems like some patients just took a bit longer to respond than others. In any case, given the data from all the trials, FDA approval for Panretin is a virtual certainty.
>>Company Press Release
SOURCE: Ligand Pharmaceuticals Inc.
Ligand's Panretin(TM) Gel Demonstrates Positive Results in Second Pivotal Phase III Trial for Aids-Related KS - NDA Planned 1Q98
SAN DIEGO, Dec. 10 /PRNewswire/ -- Ligand Pharmaceuticals Inc. (Nasdaq: LGND - news) announced today the positive results of its North American Phase III pivotal trial for Panretin Gel in patients with AIDS-related Kaposi's sarcoma (KS). In the trial, 35.1 percent of patients treated topically with Panretin Gel experienced complete or partial response compared to 17.9 percent using a placebo (vehicle gel with no active ingredient). Based on the results of both the North American and international Phase III trials, which were launched under a U.S. Investigational New Drug (IND) application, the Company intends to file a U.S. New Drug Application (NDA) in the first quarter of 1998. The Company believes Panretin Gel would be the first NDA submitted to the FDA for a topical product to be used in the treatment of KS.
Patients in the Panretin Gel group had the option of continuing treatment after the blinded portion of the study was complete. The response rate (complete and partial response) for patients initially assigned to Panretin Gel using all currently available data from the blinded phase through the open-label phase is 49.3 percent (66 of 134 patients).
Patients who were initially assigned to placebo could begin Panretin Gel therapy after the blinded phase. For those 86 patients who elected to receive Panretin Gel, the response rate was 29.1 percent (25 of 86 patients) after recalibrating the measurements of the baseline lesions prior to starting the open-label phase.
In August 1997, an international Phase III trial of Panretin Gel in patients with AIDS-related KS was stopped early because an interim analysis specified in the protocol showed a 42 percent (15 of 36 patients) response to Panretin Gel(TM) compared with 7 percent (3 of 46 patients) response to placebo.
''We are pleased with the results of Panretin Gel's pivotal trials for the treatment of cutaneous KS lesions, and will continue preparation for filing an NDA in the first quarter of 1998. If approved, Panretin Gel will likely be the first topical treatment approved for this disfiguring and debilitating disease. We believe the topical product will find a unique role in this therapeutic market and, if ongoing studies to expand its utility in additional indications are successful, Panretin Gel would quickly become an interesting first revenue product,'' said Ligand Chairman, President and CEO David E. Robinson.
''Panretin Gel differs from currently available therapies such as chemotherapy and cryotherapy in that it is a patient-controlled form of therapy that can be administered on an outpatient basis, is non-invasive and has exhibited a very tolerable side effect profile in clinical trials,'' said Richard Yocum, M.D., Medical Director, Clinical Research at Ligand, who was the principal medical monitor for the Panretin Gel trials.
Study Design
Both the North American and international Phase III trials were randomized, double-blind, placebo-controlled, 12-week studies of topical Panretin Gel in the treatment of cutaneous AIDS-related KS. The objectives of the trials were to compare the efficacy of Panretin Gel (containing 0.1% 9-cis-retinoic acid as the active agent) to placebo when applied topically, and to determine the safety and tolerability of the formulation in this patient group.
The protocols for the Phase III trials called for patients to be treated with either Panretin Gel or placebo, applied two to four times daily to cutaneous KS lesions for at least 12 weeks. Patients were assessed at two, four, eight and 12 weeks after trial entry and responses were defined using AIDS Clinical Trial Group (ACTG) criteria applicable to topical therapy of designated KS index lesions. After 12 weeks, qualifying patients could continue treatment with open-label Panretin Gel.
North American Trial Results
Of 268 patients with biopsy confirmed KS, 134 received initial therapy with Panretin Gel and 134 were treated initially with placebo.
Thirty-five percent of patients treated with Panretin Gel had a complete or partial response as compared with 17.9 percent of patients treated with placebo (p=0.002). ''The results of three clinical trials of more than 500 patients are consistent and clearly demonstrate the activity of Panretin Gel in Kaposi's sarcoma associated with AIDS. The meaningful response rate of almost 30 percent for the patients who initially were assigned to placebo but then went on to open-label Panretin Gel treatment further points to the activity of Panretin Gel in this disease,'' according to Steven D. Reich, M.D., Ligand Senior Vice President, Clinical Research.
International Trial
The international Phase III trial of Panretin Gel(TM) in patients with AIDS-related KS included 82 patients in the interim analysis. Fifteen of 36 patients (42%) on Panretin Gel achieved complete or partial response versus only three of 46 patients (7%) patients on placebo, a result that was statistically significant at a ''p value'' of 0.00027. The trial, conducted at approximately 30 centers internationally, 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 Gel treatment. A total of 132 patients were enrolled by the conclusion of the trial and will be included in the final report to the FDA. This study also will be used to file a Marketing Authorization Application in Europe.
Kaposi's Sarcoma
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. From that time until the HIV disease epidemic identified with AIDS, KS remained a rare tumor.
Panretin(TM) Oral Capsules
Panretin(TM) Oral is in single-agent Phase II trials and in a Phase I trial in combination with interferon for patients with AIDS-related Kaposi's sarcoma. Phase II trials are ongoing in breast, ovarian, and pediatric cancers, bronchial metaplasia and myelodysplastic syndrome, and a study in severe plaque psoriasis has 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 Oral is also in Phase III pivotal trials 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 statement 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 Gel, or any product in the Ligand 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. Ligand undertakes no obligation to update the statements contained in this press release after the date hereof.
SOURCE: Ligand Pharmaceuticals Inc.<< |
