International Approvals: Ebixa, Depromel/Luvox, M-Vax

Yael Waknine

October 18, 2005

Oct. 18, 2005 — The European Commission has approved memantine HCl for the treatment of moderate Alzheimer's disease; Japan's Ministry of Health, Labor, and Welfare has approved fluvoxamine maleate for the treatment of social anxiety disorder; and the Swiss regulatory authority Swissmedic has approved an autologous cell vaccine for the treatment of stage 3 and 4 melanoma.


Memantine (Ebixa) for the Treatment of Moderate AD in EU

On Oct. 12, the European Commission approved an expanded indication for memantine HCl (Ebixa, made Merz Pharma GmbH & Co. and marketed by H. Lundbeck A/S), allowing its use for the treatment of moderate Alzheimer's disease (AD). The drug was previously approved for the treatment of moderately severe and severe AD.

The approval was based on the results of a meta-analysis from six international phase 3 placebo-controlled, six-month studies that showed a statistically significant effect in favor of memantine therapy for the cognitive, global, and functional domains of the Mini Mental-State Examination (MMSE) in patients with moderate to severe AD (baseline MMSE score < 20).

Further analysis showed that twice as many memantine-treated patients showed a statistically significant reduction in marked clinical worsening for all three domains compared with those who received placebo.

Memantine HCl (Namenda, made by Forest Laboratories, Inc., under license from Merz Pharma GmbH & Co.) is approved by the U.S. Food and Drug Administration for the treatment of moderate to severe AD.


Fluvoxamine Maleate (Depromel/Luvox) for Social Anxiety Disorder in Japan

On Oct. 11, Japan's Ministry of Health, Labor, and Welfare (MHLW) approved a new indication for fluvoxamine maleate (Depromel, made by Meiji Seika/Luvox and Solvay Seiyaku, and marketed by Astellas Pharma, Inc.), allowing its use in daily doses ranging from 50 to 160 mg for the treatment of social anxiety disorder (SAD).

The approval was based on data from a 10-week clinical trial in adults that confirmed the efficacy of fluvoxamine therapy for SAD, as evaluated using the Liebowitz Social Anxiety Scale Japanese Version. Results showed that treatment with fluvoxamine decreased anxiety related to social situations and also suppressed avoidance of such situations, thereby increasing patient quality of life.

Adverse events reported by fluvoxamine-treated patients in the study were similar to those observed in studies of the drug for depression and obsessive-compulsive disorder.

Fluvoxamine (50-160 mg/day) was previously approved by Japan for the treatment of depression and obsessive-compulsive disorder. It is approved by the U.S. Food and Drug Administration for obsessive-compulsive disorder in patients aged 12 years and older.


Melanoma Vaccine (M-Vax) Approved in Switzerland

The Swiss regulatory authority Swissmedic approved in October an autologous cell vaccine (M-Vax, made by AVAX Technologies, Inc., and marketed by Pro Vaccine AG) for the treatment of stage 3 and 4 melanoma.

The vaccine is formulated by adding the hapten dinitrophenyl (DNP) to a sample of the patient's melanoma cells.

Treatment consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with bacilli Calmette-Guerin as an immunological adjuvant. In most patients, the vaccine induces a delayed-type hypersensitivity (DTH) to the DNP-modified melanoma cells; about 50% of patients also exhibit DTH to unmodified tumor cells.

The approval was based in part on data from a study of 214 patients with clinically evident stage 3 melanoma, showing that postlymphadenectomy vaccine therapy yielded a five-year survival rate of 44% that compared favorably with the reported surgical rate of 20% to 25%.

Results also showed a statistically significant positive relationship between induction of DTH response to unmodified autologous tumor cells and survival.

In another trial, the vaccine elicited antitumor responses in 11 of 83 patients with stage 4 melanoma with measurable metastases (complete response, 2; partial response, 4; mixed response, 5).

Consideration was also given to unpublished safety and efficacy data from a clinical trial in more than 400 stage 3 and 4 melanoma patients. The most commonly reported adverse reactions to the vaccine included mild nausea, vomiting, and injection-site reactions (papules or pustules).

The vaccine has been granted orphan drug status for this indication in the U.S. and is currently being considered for approval in France. It is approved for compassionate use in Spain and Belgium, and was previously approved for use in Australia but was withdrawn from the market in September 2002 due to company financial constraints.

According to a company news release, additional clinical trials are expected to begin in the U.S. and France by the end of 2005 to evaluate the drug's safety and efficacy in patients with non-small cell lung cancer, metastatic ovarian cancer, and metastatic colorectal cancer.

Reviewed by Gary D. Vogin, MD

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