Valeant Receives FDA Marketing Approval for Cannabinoid Cesamet

Valeant Pharmaceuticals Receives FDA Marketing Approval for Cannabinoid Cesamet

COSTA MESA, Calif., May 16, 2006 -- Valeant Pharmaceuticals International today announced that the U.S. Food and Drug Administration (FDA) has given marketing approval for Cesamet (CII) (nabilone) oral capsules. Cesamet is used to treat nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional anti-emetic treatments.

"There is still a significant unmet need in treating one of the most feared and severe consequences of life-saving cancer therapies," said Timothy C. Tyson, Valeant's president and chief executive officer. "With the approval of Cesamet, Valeant is proud to offer a solution that will help alleviate one of the most common side effects of chemotherapy."

Cesamet is a synthetic cannabinoid that is thought to act as an omnineuromodulator - interacting with the cannabinoid receptor, CB1, which is present throughout the nervous system. This receptor is involved in regulating nausea and vomiting. Because of this omnineuromodulation, the mechanism of action for Cesamet is significantly different from conventional anti-emetics. Cesamet has a long duration of action, which allows for less frequent dosing, typically twice daily.

Valeant acquired Cesamet from Eli Lilly & Company in 2004 and currently sells Cesamet in Canada, where the product has an 86 percent share of the cannabinoid market, according to IMS Compuscript data from February 2006. Last year, Valeant entered into an agreement with Par Pharmaceutical Companies, Inc. to promote Cesamet in the United States. Valeant anticipates launch of Cesamet in the next several weeks following approval.

"In my practice, Cesamet has been used successfully to treat patients with chemotherapy-induced nausea and vomiting," said Paul Daeninck, M.D., assistant professor, Department of Oncology at the University of Manitoba in Winnipeg, Canada. "We have found that it offers long-acting chemotherapy-induced nausea and vomiting relief in a well-tolerated and convenient twice-a-day regimen."

The American Cancer Society estimates that there will be nearly 1.4 million new cancer cases in 2006. Approximately 70 to 80 percent of all patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV). Although the use of anti-emetic agents decreases the incidence and severity of CINV, symptoms continue to occur in 40 to 60 percent of patients.

"There is a need for cannabinoids, such as Cesamet, for patients who have exhausted conventional treatments but are still coping with the debilitating side effects of chemotherapy," said Neal Slatkin, M.D., DABPM and director, Department of Supportive Care, Pain and Palliative Medicine at City of Hope. "CINV dramatically impacts cancer patients' quality of life and can result in patients refusing courses of chemotherapy, which minimizes chances for the best possible outcome."

Cesamet Clinical Trial Overview

Cesamet was evaluated for its effectiveness and safety in the treatment of nausea and vomiting induced by cancer chemotherapy in patients receiving a wide variety of chemotherapy regimens, including low-dose cisplatin (20 mg/m2) in both placebo-controlled and active controlled (prochlorperazine) trials. Efficacy and safety results were derived from eleven well-controlled anti-emetic, double-blind, crossover studies with optional continuation into Cesamet open-label therapy. Either prochlorperazine or placebo was used as the comparator. The prochlorperazine-controlled studies consisted of two flexible-dose, crossover studies (143 patients of which 112 were evaluable for efficacy) and three fixed-dose, crossover studies (126 patients of which 73 patients were evaluable for efficacy). The placebo-controlled studies were six fixed-dose, crossover studies (199 patients of which 129 were evaluable for efficacy). The crossover studies comprised two cycles of cancer treatment, Cesamet in one cycle and control drug in the other. The order of cycles for each patient was randomized. The most frequent dose regimen of nabilone was 2 mg BID (twice-a-day), except in the two flexible-dose studies, where Cesamet daily doses of over 4 mg were frequent. Efficacy was evaluated by comparing the number of vomits and the severity of nausea.

All statistical comparisons significantly favored nabilone, with the exception of one prochlorperazine-controlled flexible-dose study. However, even in this study, nabilone had a lower overall average frequency of vomits and a lower average severity of nausea score than prochlorperazine.

Important Safety Information

Cesamet, a synthetic cannabinoid similar to the active ingredient found in naturally occurring Cannabis sativa L (marijuana; delta-9-THC), is contraindicated in any patient who has a history of hypersensitivity to any cannabinoid. Patients receiving treatment with Cesamet should be specifically warned not to drive, operate machinery, or engage in any hazardous activity while taking Cesamet. During controlled clinical trials of Cesamet, virtually all patients experienced at least one adverse reaction. The most commonly encountered events were drowsiness, vertigo, dry mouth, euphoria (feeling "high"), ataxia, headache, and concentration difficulties. Cesamet should not be taken with alcohol, sedatives, hypnotics, or other psychoactive substances because these substances can potentiate the central nervous system effects of nabilone. Since Cesamet can elevate supine and standing heart rates and cause postural hypotension, it should be used with caution in the elderly, and in patients with hypertension or heart disease. Cesamet should also be used with caution in patients with current or previous psychiatric disorders (including manic depressive illness, depression and schizophrenia), as the symptoms of these disease states may be unmasked by the use of cannabinoids. Caution must be used when administering Cesamet in combination with any CNS depressant.

Cesamet should be used with caution in patients with a history of substance abuse, including alcohol abuse or dependence and marijuana use, since Cesamet is similar to the active ingredient found in naturally occurring marijuana. Cesamet should be used with caution in pregnant patients, nursing mothers, or pediatric patients because it has not been studied in these patient populations.

Source: Valeant

Posted: May 2006


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