Washington Editor

Preliminary results from a pivotal Phase III trial of Alkermes Inc.'s Vivitrex indicate that a once-monthly injection, along with psychosocial therapy, helps men reduce their rate of heavy drinking. However, the drug does not appear to work as well in women.

Alkermes, of Cambridge Mass., on Monday released favorable preliminary data from a six-month trial that enrolled 624 people described as heavy drinkers (five drinks a day for men and four for women). Trial participants were randomized to receive a combination of therapy plus once-monthly injections of 380 mg of drug, 190 mg of drug or placebo.

As it turns out, men in the 380-mg group demonstrated a 48 percent reduction in the rate of heavy drinking relative to placebo, a highly statistically significant outcome (p<0.0001), the company said. Women in the same group, however, showed no significant difference from placebo.

"This result is particularly striking when one considers that this difference is a 48 percent reduction from a placebo group whose drinking activity is also declining during the study due to the positive impact of psychosocial counseling and, possibly, the psychological impact of the placebo injection," Elliot Ehrich, Alkermes' chief medical officer, said during a conference call Monday.

The results then beg the question, why didn't females respond as well?

"Based on our analysis in prior studies, we had prepared for different responses to gender," Ehrich said. "However, we were surprised at the extent of the difference. We have a lot more work to do here in order to understand the results and we would expect to identify and pursue clinically various hypotheses in the future."

Two-thirds of patients in the study were male, which is representative of the alcohol-dependent population, the company said.

In the overall study population, patients treated with 380 mg of drug experienced about a 25 percent reduction in the rate of heavy drinking relative to placebo, a statistically significant number (p=0.03). And in the overall 190-mg group, patients in the treatment arm experienced a 17 percent reduction in the rate of heavy drinking relative to placebo with a trend toward statistical significance (p<0.10).

Men in the treatment arm of the 190-mg group demonstrated a 25 percent reduction in the rate of heavy drinking, also statistically significant (p<0.03).

While the overall study population produced statistically significant results, Ehrich cautioned that it would be incorrect to infer that reduction is representative of the treatment effect across all patients when, in fact, the entire effect was observed in the male population.

Vivitrex is a long-acting formulation of naltrexone based on Alkermes' Medisorb injectable extended-release technology. Using the technology, naltrexone is encapsulated in microspheres made of a biodegradable polymer that dissolves slowly and releases drug at a controlled rate following intramuscular injection.

Richard Pops, Alkermes' CEO, told BioWorld Today complete results of the Phase III will be submitted for publication in a peer-reviewed journal. He declined to speculate on a timeline for publication.

However, he did say the company hopes to file for regulatory approval in the U.S. in the first half of 2005. The application will be based on the single Phase III.

Despite a great level of interest in Vivitrex, Pops said, the company hasn't decided whether to partner the product in the U.S. The company likely will seek a partner for markets abroad, though.

In the weeks prior to learning of Vivitrex's potential, the FDA approved Risperdal Consta (risperidone, long-acting injection) for schizophrenia. Alkermes' partner, Janssen Pharmaceutica Products LP, a unit of Johnson & Johnson, of New Brunswick, N.J., launched the product last week. (See BioWorld Today, Oct. 31, 2003.)

As for the success of both Risperdal Consta and Vivitrex, Pops said the company has accomplished two of its major milestones for 2003. "In terms of fundamentals of the company, as we go forward into 2004, we feel we are on strong footing," he said.

Alkermes' stock (NASDAQ:ALKS) closed Monday at $12.78, down 25 cents.