Alkermes Inc. applied for FDA approval of Vivitrex (naltrexone long-acting injection) to treat alcoholism, making it the first injectable product filed for the indication.
The drug delivery company submitted a new drug application to market Vivitrex for alcohol dependence. The product, a reformulated version of a long-approved alcohol treatment drug, would be used as a once-monthly injection. It employs Alkermes' Medisorb technology to encapsulate naltrexone in microspheres that dissolve slowly, releasing the drug at a controlled rate following intramuscular injection.
"Alcohol dependence is a very serious disease, and it affects behavior through brain mechanisms that have to do with reward," said David Gastfriend, Alkermes' vice president of medical affairs. "The data in our submission supports the significant benefit of our medication, Vivitrex, in combination with counseling for patients with alcohol-dependence."
Vivitrex is delivered during office visits, during which patients also receive concurrent counseling, which Gastfriend labeled "a learning process."
The company, of Cambridge, Mass., estimated that 18 million people comprise the alcohol-dependence market in the U.S., with about 2.3 million adults seeking treatment each year. Products already marketed in the indication include two off-patent products, standard naltrexone and Antabuse (disulfiram), which causes an unpleasant reaction when alcohol is ingested, and the newly approved Campral (acamprosate, from Forest Laboratories Inc.). The latter was cleared for maintenance of alcohol abstinence in patients who are abstinent at treatment initiation.
The drugs already on the market also are used in combination with counseling.
"What's unique about Vivitrex is that it's a single injection that lasts not for a day, but for 30 days," Gastfriend told BioWorld Today. "So the continuity of that concentration in the bloodstream" gives confidence that the biological foundation of the drug is being sustained.
He added that because the drug is delivered intramuscularly, rather than through gastrointestinal channels, more of the active ingredient gets into the bloodstream without passing through the liver to avoid first-pass hepatic metabolism.
The application is based largely on data from a single pivotal trial that showed a 380-mg dose of the drug to be particularly effective among males. They demonstrated a 48 percent reduction in the rate of heavy drinking relative to placebo (p<0.0001), a statistically significant difference relative to that primary endpoint. In the overall study population, patients treated with the same dose of Vivitrex experienced about a 25 percent reduction in the rate of heavy drinking relative to placebo (p<0.025), also a statistically significant difference. That latter reduction translates to lowering an alcoholic's monthly heavy drinking days from 19 to three.
"That reduction in heavy drinking is the parameter with the strongest correlation to disease, health and injury," said Gastfriend, who before joining Alkermes served as a principal investigator at one of 24 sites at which the trial was conducted. "It's a well-accepted metric for measuring outcome."
Two-thirds of patients in the 624-subject study were male, which is representative of the alcohol-dependent population. Gastfriend said the trial was not designed to test differences between men and women, but added that women tolerated the drug as well as men, retention rates were similar in both groups and women were interested in continuing the therapy at the same rate as men. Treatment with both the drug and placebo was accompanied by counseling, and Vivitrex's safety and tolerability profiles proved positive. In the past, the company indicated that the Phase III study's full data would be published in a peer-reviewed journal. (See BioWorld Today, Dec. 9, 2003.)
Also in the study, men in a 190-mg group demonstrated a 25 percent reduction in the rate of heavy drinking, also statistically significant (p<0.03). But Alkermes, which owns all rights to Vivitrex, has applied solely for approval of the 380-mg dose.
"This is the first proprietary agent in the Alkermes portfolio," Gastfriend said, "so this is an important step for our company. Considerations about partnering are well under way." He added that should a partnership not be secured before launch, Alkermes is prepared to build a small internal sales force.
The company already has experience with a commercial product and related partnership through its drug, Risperdal Consta (risperidone long-acting injection), a long-acting atypical antipsychotic for schizophrenia. It is marketed worldwide by Janssen-Cilag, a wholly owned subsidiary of Johnson & Johnson, of New Brunswick, N.J.
Still in Alkermes' development pipeline are other extended-release injectable products and pulmonary drug products based on its delivery technology. Its primary research areas lie in diseases of the central nervous system and diabetes.
On Friday, its shares (NASDAQ:ALKS) dropped 37 cents to close at $10.01.