Early Clinical Results of Ligand's Novel RAR-Selective Retinoid, LGD1550 Reported at ASCO Meeting In Los Angeles
PR Newswire - May 18, 1998 17:30
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Additional studies planned for cervical, head and neck cancer
LOS ANGELES, May 18 /PRNewswire/ -- Investigators reported today at the 34th Annual American Society of Clinical Oncology (ASCO) meeting in Los Angeles that Ligand (LYE-gand) Pharmaceuticals Incorporated (Nasdaq: LGND) compound, LGD1550, has been well-tolerated in Phase I/II clinical trials in advanced cancer. LGD1550 is a retinoic acid receptor (RAR)-selective retinoid that has shown potent anti-tumor activity in pre-clinical animal studies. Results from two independent Phase I/II trials conducted at Memorial Sloan- Kettering Cancer Center and at Georgetown University Lombardi Cancer Research Center were reported at the meeting.
According to Steven D. Reich, M.D., Senior Vice President of Clinical Research at Ligand, "These preliminary results from our initial human clinical trials support exploration of the potential efficacy of LGD1550. Data generated from animal squamous cell cancer models of LGD1550 therapy, coupled with the favorable safety profile in our initial human studies, support Ligand's plans to implement additional studies with LGD1550 in combination with chemotherapy for the treatment of cervical cancer and head and neck cancer."
The objectives of the two Phase I/II trials, which were similar in design, were to evaluate the tolerability, safety, and pharmacokinetics of LGD1550 capsules to determine the maximum tolerated dose, and to evaluate the potential efficacy of LGD1550 in patients with advanced cancer. The studies were open-label, dose-escalation studies in which a minimum of three patients were treated at each dose level.
A treatment duration of four weeks was the intended duration of treatment with the option for longer duration therapy if patients were judged to have clinical benefit with no unacceptable toxicities.
Investigators from Memorial Sloan-Kettering led by Raymond P. Warrell, Jr., M. D., Attending Physician at Memorial Sloan-Kettering Cancer Center and Professor of Medicine, Cornell University Medical College, reported results from 23 patients enrolled in seven dose levels ranging from 20 mcg/m2/day to 400 mcg/m2/day administered as a single daily oral dose. Primary cancer diagnoses included: thyroid (seven patients); non-small cell lung (five patients); prostate (three patients); leiomyosarcoma (two patients); bladder (two patients); and renal, adenoid cystic, nasopharyngeal and neurodendocrine cancers (one patient each).
With limited information from the higher dose levels, Memorial Sloan- Kettering investigators observed no dose-limiting toxicities and observed only minor adverse events in LGD1550 treated patients. The maximum tolerated dose has not been determined. Unlike all-trans retinoic acid, a retinoid approved for the treatment of acute promyelocytic leukemia, LGD1550 does not appear to induce its own metabolism over the dose range tested since blood levels are maintained with continued therapy.
"LGD1550 has been well tolerated with only minor adverse effects of dry skin and fatigue observed at the doses studied," according to Steven L. Soignet, M. D., Fellow, Developmental Chemotherapy Service, Memorial Sloan- Kettering Cancer Center, who presented the data from the Memorial Sloan- Kettering study.
In the second Phase I/II trial, investigators from Georgetown University, led by Michael J. Hawkins, M.D., Associate Professor of Medicine, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, reported results from 33 patients enrolled in eight dose levels ranging from 20 mcg/m2/day to 400 mcg/m2/day as a single daily oral dose. Primary cancer diagnoses included: non-small cell lung (nine patients); prostate (six patients); head and neck (five patients); colon (three patients); renal cell (two patients); unknown primary (two patients); breast (2 patients); and anal, ovarian, thymoma and liposarcoma cancers (one patient each). Investigators observed dose-limiting skin toxicities during the first four weeks of therapy at 240 mcg/m2/day, 300 mcg/m2/day and 400 mcg/m2/day, and they have observed dose-limiting diarrhea and abdominal cramps at 400 mcg/m2/day. The maximum tolerated dose or recommended Phase II dose has not yet been determined.
"Dose-limiting toxicities, such as headache and lipid abnormalities frequently observed with other retinoids, have not been observed with LGD1550 to date," said Dr. Naiyer Rizvi, Assistant Professor of Medicine, Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, who presented the data from the Georgetown University trial.
The Company plans to begin Phase II studies with LGD1550 in patients with cervical and head and neck cancers after determining the recommended dosage levels, which will be based on review of Phase I data.
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 LGD1550 capsules, or any product in the Ligand pipeline, will be successfully developed, that later stage human clinical data will be consistent with preclinical data, 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, 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
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