Here's Panretin topical:
Studies Presented At 12th International AIDS Conference
Support Ligand's Panretin Gel Effectiveness in Controlling
Dermal Lesions in Aids-Related Kaposi's Sarcoma
Business Wire - June 30, 1998 09:21
%LIGAND LGND %CALIFORNIA %MEDICINE %PHARMACEUTICAL V%BW P%BW
GENEVA, Switzerland--(BW HealthWire)--June 30, 1998--
Up to 50 Percent of Patients Studied Experienced Clearing/Reduction of Lesions; Tumor Reduction
Observed Independent of Concurrent Antiretroviral Therapy
Scientists participating in the 12th International AIDS Conference in Geneva today presented data
from two Phase III studies demonstrating that Ligand (LYE-gand) Pharmaceuticals Incorporated's
(NASDAQ:LGND) Panretin(R) gel (alitretinoin) 0.1% is clinically effective in treating dermal lesions of
AIDS-related Kaposi's sarcoma (KS) in up to 50 percent of patients studied.
These data further support previous safety and efficacy findings for Panretin gel reported in earlier
investigations. The data presented today were used to support a New Drug Application (NDA) which
Ligand submitted to the U.S. Food & Drug Administration on May 26, 1998.
Patient responses to Panretin gel in Phase III investigations were significant enough that one of the two
studies, the results of which were presented today, had stopped enrollment early in accordance with
the study's protocol after an 82-patient interim analysis. The interim analysis concluded that patients
treated with Panretin gel were six times more likely to have shown a complete or partial regression of
KS lesions compared to patients receiving a vehicle gel without active ingredient as a placebo control.
Reported for the first time today was the 134-patient final analysis which confirmed the positive results
of the interim analysis.
A second trial showed that 35 percent of patients receiving Panretin gel demonstrated either a
complete or partial response compared to only 18 percent of those receiving vehicle gel. This
investigation also included an open-label follow-on phase of treatment. Results from the open-label
portion of the study showed that nearly one out of every two patients (49 percent) exhibited a
complete or partial response to therapy with Panretin gel.
Side effects in both trials were principally confined to local skin irritations, pain and erythema and were
easily managed, according to investigators. Patient disease status and response rates were evaluated
using the AIDS Clinical Trial Group (ACTG) criteria as applied to topical therapy of cutaneous lesions.
"The scientific presentations made in Geneva today support the growing body of clinical evidence that
Panretin gel has significant potential as a therapeutic in the management of AIDS-related KS," said
Ligand chairman, president and chief executive officer David E. Robinson. "With our recent NDA
submission, we hope to bring this non-invasive and less toxic therapy to KS patients and the physicians
who treat them as rapidly as possible."
50 Percent Response Strongest Panretin Gel Data Reported to Date
The data from the North American trial were presented by Dr. Alvin Friedman-Kien of New York
University's Ronald O. Perelman Department of Dermatology. This trial, conducted by the North
American Panretin Gel KS Study Group, involved 268 patients at 35 medical centers (32 in the U.S.
and three in Canada). HIV-positive patients with biopsy-proven KS were randomized to receive
Panretin gel or vehicle gel, with treatment intended to last 12 weeks. Evaluation of six index lesions
was conducted at least every four weeks.
Treatment and control arms were well matched as to baseline CD4+ count (median 154 cells/mm3
compared to 144 cells/mm3); percentage receiving prior systemic therapy for KS (36 percent
compared to 34 percent) and prior topical/local anti-KS therapy (49 percent compared to 53
percent). The percentage receiving concurrent antiretroviral (ARV) therapy included: any ARV (93
percent compared to 93 percent), three or more ARV (72 percent compared to 79 percent) and
protease inhibitors (74 percent compared to 82 percent).
The overall response (complete or partial) determined by applying ACTG criteria to each patient's six
index lesions was 35 percent (47 of 134 patients) for Panretin gel compared to 18 percent (24 of 134
patients) for patients receiving vehicle gel. The cumulative response rate for all patients treated with
Panretin gel, including the follow-on open-label phase, was 49 percent (90 of 184 patients), with two
patients experiencing a complete clearing of all index lesions.
"Response to Panretin gel was very clear in nearly half of all patients studied," said Dr. Friedman-Kien,
principal investigator. "Even more provocative, however, is our finding that responses remained
statistically significant even after adjusting for ARV therapy. Clinicians evaluating Panretin gel may have
questioned whether it is the antiretrovirals or the gel that is impacting tumor growth. This study
indicates that Panretin gel provides an anti-tumor effect independent of AVR therapy."
Tumor regression among the control group correlated with the degree of ARV therapy, but after
adjusting for concurrent ARV therapy, response rates for Panretin gel remained substantially higher
(p=0.0015) than the control. Patient quality-of-life responses were also higher in the study's Panretin
gel arm.
Researchers also noted the benefits of the drug's easy application, strong compliance rates, limited and
manageable side effects and, most encouraging, responses among patients who had previously failed
chemotherapy treatment or had CD4+ counts below 50 cells/mm3.
Final Results Reported for International Study
Also reported today by Neil Bodsworth, M.D., director and research program coordinator at the
Taylor Square Private Clinic, Sydney, Australia, was a further analysis of results from an international
Phase III study. The study was conducted at 22 enrolling sites in Australia, the United States and
Europe. This trial was designed to evaluate the effectiveness of Panretin gel in the palliative treatment of
cutaneous AIDS-related KS.
Patient accrual was halted in August 1997 after a planned interim data analysis found that patients
receiving Panretin gel were significantly more likely to improve than those receiving the control, or
vehicle, gel. With 82 evaluable patients enrolled, researchers were able to determine a statistically
significant drug response -- with a "p value" of 0.00027 -- and accrual was stopped.
"While a portion of these data have been previously reported," said Dr. Bodsworth, "we are
particularly excited by the final results, which confirm the positive findings from the interim analysis."
The final analysis included 134 patients. Patients assigned active gel were significantly more likely than
placebo patients to respond to treatment (37 percent compared to 7 percent). The study's treatment
arms -- Panretin gel compared to vehicle gel -- were well matched for various demographic factors as
well as CD4+ cell count at baseline (160 cells/mm3 compared to 132 cells/mm3); proportion receiving
any ARV on study (92 percent compared to 96 percent), and protease inhibitor (73 percent
compared to 81 percent) and any triple or greater ARV combination (73 percent compared to 82
percent).
All patients completing the trial were eligible to receive Panretin gel following the study's termination.
Of the 134 patients, 99 patients continued treatment with Panretin gel.
Kaposi's Sarcoma
KS is the most frequent AIDS-related malignant cancer and is often characterized by multifocal,
widespread lesions. 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.
Value of Retinoids in Cancer Therapy
Panretin gel and Panretin(R) capsules (alitretinoin) are two Ligand-developed retinoid-based drugs that
have reached advanced stages of testing. These products can be described as vitamin A derivatives
which are designed to act selectively on diseased or malfunctioning cells. Current treatments for many
diseases, including cancers such as KS, often have serious unwanted toxic effects that can impede
aggressive treatment regimens and negatively impact quality of life.
In addition to the Panretin gel trials, the oral form of Panretin has been studied in two Phase II trials for
the treatment of AIDS-related KS. Panretin capsules are also being evaluated in an NCI-sponsored
Phase I trial in combination with interferon for patients with AIDS-related KS. Research on Panretin
capsules for the treatment of KS is also being presented today at the International AIDS Conference.
Phase II trials with Panretin capsules are ongoing in breast and pediatric cancers, and in bronchial
metaplasia. Phase II trials 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 Transducer 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 diseases.
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(R), or any product in the Ligand pipeline, will be successfully
developed, that subsequent clinical trials will be supportive of additional regulatory filings, that
regulatory filings will be made on a timely basis, or at all, that regulatory approvals will be granted, that
patient and physicians 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.
Ligand Pharmaceuticals' releases are available via fax at no charge by calling 888/329-9832 or on the
world wide web at www.businesswire.com/cnn/lgnd.htm
CONTACT: Ligand Pharmaceuticals Incorporated
Susan Atkins, 619/550-7687
Mary Kenny, 619/550-7536
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