Ligand Submits New Drug Application for Panretin(R) Gel in AIDS-Related Kaposi's
Sarcoma
PR Newswire - May 27, 1998 17:36
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- Milestone Marks Company's First NDA -
SAN DIEGO, May 27 /PRNewswire/ -- Ligand (LYE-gand) Pharmaceuticals Incorporated (Nasdaq: LGND) announced today that the Company
has submitted its first new drug application (NDA) to the U.S. Food and Drug Administration for Panretin(R) gel (alitretinoin) 0.1% for the
treatment of patients with AIDS- related Kaposi's sarcoma (KS). If approved, Panretin gel would provide the first topical therapy for KS, a
cancer common in people who have AIDS.
The NDA is based on two multicenter, randomized, double-blind, vehicle- controlled Phase III clinical trials; one conducted internationally at
30 sites in Europe, Australia and the U.S., and one conducted at 35 sites in North America. The international trial was halted early in August
1997 after only 82 patients had been evaluated because a planned interim analysis of data demonstrated Panretin gel's activity to meet the
targeted efficacy stopping rules; 42 percent of patients in the treatment group showed a response to therapy compared to only seven percent
of those in the study's vehicle gel treatment arm, a "p-value" of 0.00027.
Final results of the North American trial, which were released in December 1997, demonstrated that 35 percent of patients treated topically with
Panretin gel experienced complete or partial response compared to 18 percent of patients applying vehicle gel (p = 0.002).
"The filing of our first NDA is an important milestone for Ligand. We are very pleased that, if approved, Panretin gel will offer a new,
non-invasive and less toxic alternative therapy to people with AIDS-related KS," said Ligand Chairman, President/CEO David E. Robinson.
"Ligand has not only realized an important clinical milestone that all biotechnology companies aspire to achieve, but we have also progressed
on our learning curve toward the establishment of the infrastructure necessary for filing three more NDAs in 1998 and 1999 for key products to
our march to profitability in 1999."
Both Phase III trials supporting the NDA submission were designed to evaluate safety and efficacy of Panretin(R) gel in patients with
cutaneous AIDS-related KS. Protocols for the trials called for patients to be treated with either Panretin gel or vehicle gel, 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. Responses were defined
using AIDS Clinical Trials Group (ACTG) criteria as applied to topical therapy of designated KS index lesions. After 12 weeks, qualifying
patients could continue treatment with open-label Panretin gel.
In all clinical trials to date, Panretin gel was generally well-tolerated. Side effects primarily included erythema or skin irritation at the application
site.
"We believe that investigations undertaken to date with Panretin gel in the 465 patients with AIDS-related KS in Ligand's clinical trials clearly
demonstrate the drug's safety and efficacy," said Steven D. Reich, M.D., Ligand Senior Vice President, Clinical Research. "The patient
response rates in our international and North American trial consistently demonstrated superiority over vehicle gel. We hope to soon be able
to provide this valuable therapy to the thousands of people who are affected each year in the U.S."
Of the patients in the North American Phase III trial randomized to Panretin gel, the median baseline CD4+ count was 154; 36 percent had
received prior systemic anti-KS therapy and 49 percent had received prior local/topical anti-KS therapy. Ninety-three percent were receiving
concurrent antiretroviral therapy, including 72 percent who were receiving three or more antiretroviral therapies. Seventy-four percent of the
patients on Panretin gel were receiving concurrent protease inhibitor therapy. Twenty percent of patients in the Panretin gel group had
baseline CD4+ counts below 50; 23 percent in the vehicle gel group had baseline CD4+ counts below 50.
"The observation that the response to Panretin gel in the North American trial increased to 49 percent in the open-label phase of the study
suggests that the full potential of the drug was not realized during the initial 12 weeks of blinded treatment. Panretin gel produced durable
responses that were not dependent on the patient's immunologic status and that occurred independently of the potential effects of concurrent,
highly active antiretroviral therapy. Responses were seen not only in patients on various anti-KS therapies, but also in patients who were
refractory to prior chemotherapy for KS," said Richard C. Yocum, M.D., Ligand Senior Medical Director, Clinical Research.
Of the patients in the International Phase III trial who received Panretin gel, the median baseline CD4+ count was 137; 95 percent were
receiving concurrent antiretroviral therapy, including 78 percent who were receiving triple or greater antiretroviral combination therapies.
Seventy-two percent of the patients on Panretin gel were receiving concurrent protease inhibitor therapy. Twenty-eight percent of patients
both in the Panretin gel group and in the vehicle gel group had baseline CD4+ counts below 50.
Kaposi's Sarcoma
Kaposi's sarcoma was first described in 1872 by the Austro-Hungarian dermatologist, Moritz Kaposi. Until the HIV disease epidemic, KS was a
rarely diagnosed tumor. However, KS is the most frequent AIDS-related malignancy seen in patients 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. The Company estimates that between 15,000 to 25,000 patients in the U.S. are affected by the disease.
Oral Form of Panretin (R) Completes Phase II Advanced Clinical Testing
Panretin(R) capsules (alitretinoin) have been studied for patients with AIDS-related Kaposi's sarcoma in two single-agent, open-label Phase II
trials and are being evaluated in a Phase I/II trial in combination with interferon. In both Phase II trials with Panretin(R) capsules in patients
with AIDS- related KS, analyses showed intent-to-treat patient response rates of 37 percent at 16 or more weeks.
The two Phase II studies were similar in design, with one conducted by the AIDS Malignancy Consortium (AMC) sponsored by NCI and the
other sponsored directly by Ligand. Both were multicenter, open-label studies designed to evaluate the safety and efficacy of Panretin
capsules in patients with AIDS- related KS.
Results from the AMC trial were presented at the National Cancer Institute's (NCI) AIDS Malignancy Conference in Bethesda, MD in April and
at the American Society of Clinical Oncology meeting on May 18. Four abstracts pertaining to Panretin studies in KS will be presented at the
12th International AIDS Conference in June in Geneva, Switzerland.
Additional Studies with Panretin Capsules
Phase II trials with Panretin capsules are ongoing in breast and pediatric cancers, and in bronchial metaplasia. A trial in myelodysplastic
syndrome and in severe plaque psoriasis have been completed. The results of the ongoing studies are expected to be announced in 1998 and
may support additional studies upon which additional NDAs could be based. In addition, Panretin capsules are planned to be studied in a
European trial in patients with acute promyelocytic leukemia.
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 results from more advanced clinical trials will be consistent with earlier results, that drug
candidates will show efficacy in all indications currently being studies, that final data will be consistent with interim data, that regulatory
approvals will be granted in a timely manner, or at all, that patient physicians 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
/CONTACT: Investors: Susan Atkins, 619-550-7687, or Media: Mary Kenny,
619-550-7536, both of Ligand Pharmaceuticals Incorporated/ |
