The first pill designed to curb a person’s urge to have more than a few drinks at a sitting is undergoing tests in Europe, promising doctors and public-health authorities a new approach to fighting alcoholism.
The drug, nalmefene from H. Lundbeck A/S in Valby, Denmark, blocks brain signals that make activities such as sex and drinking feel good. Should trials succeed, the medicine may win clearance in Europe as early as 2012, becoming the first new alcoholism treatment approved there in more than 15 years.
While the drugs now sold are used to prevent relapses after people quit drinking, nalmefene is aimed at reducing consumption without the abstinence that Alcoholics Anonymous and other treatment programs say is necessary. This less-strict approach may drive more abusers to seek treatment for the first time, said Adron Harris, director of the University of Texas at Austin’s Waggoner Center for Alcohol & Addiction Research.
“A major problem among alcohol abusers is that many are not interested in seeking treatment, perhaps because they do not want to accept the goal of complete abstinence,” Harris said.
The drug’s effects may prove greater on public health than on Lundbeck. Peter Welford, a London-based analyst at Jefferies International Ltd., said nalmefene may have peak sales for alcohol dependence of about $60 million a year, in 2018. That’s equivalent to a fraction of the $2.57 billion in total revenue for the company last year.
Welford’s estimate was held down by uncertainty over what price Lundbeck could demand and whether health-care providers would embrace a drug-based approach to treatment, he said.
“The market remains an untapped gold mine,” said Welford, who recommends buying Lundbeck shares.
Lundbeck rose 0.4 percent to 103.40 kroner at 5:06 p.m. in Copenhagen trading, giving the company a market value of 20.3 billion kroner ($3.6 billion). Of 17 Lundbeck analysts tracked by Bloomberg, 9 say investors should buy the shares, while 5 have “sell” opinions and 3 say “hold.”
Programs such as New York-based Alcoholics Anonymous, founded in 1935, require people to abstain. Choosing not to drink at all may be more effective than trying to curb consumption, according to a U.K. study published in March in Alcohol & Alcoholism, a journal of the London-based Medical Council on Alcohol. Drinkers who had sought treatment and abstained had fewer days of relapse when they imbibed too much, the researchers found.
“Many people make a decision to stop drinking,” said Peter McCann, a recovered alcoholic who is co-founder of Castle Craig Hospital, a rehabilitation clinic near Edinburgh. “They don’t need drugs to stop.”
It would be a great help to patients if nalmefene works, said Marvin D. Seppala, chief medical officer of Hazelden, the Center City, Minnesota-based treatment center whose abstinence-based approach has been adopted in more than 40 countries. Seppala said he is cautious about prescribing medicines without abstinence, having worked with patients who tried to curb intake by taking naltrexone, a generic drug not developed for that purpose.
Naltrexone cuts the desire to drink by blocking the release of dopamine, a brain chemical that generates feelings of pleasure. The drug is approved as a treatment for people who have stopped drinking, and has been taken experimentally to reduce consumption without quitting alcohol. The medicine didn’t help the patients curb intake, Seppala said.
“They were unable to do anything that would be considered beneficial, going from a liter a day of distilled spirits to two drinks short of a liter,” Seppala said in an e-mail interview.
In September, the London-based European Medicines Agency, concerned that the all-or-nothing approach leaves millions untreated, included consumption-cutting medicines in its first guidelines to drugmakers on how to test experimental alcohol treatments. The London-based National Institute for Health & Clinical Excellence, or NICE, an adviser to the U.K.’s National Health Service, is considering new guidelines that recommend medication if other approaches fail.
There is a “critical need” for drugs to reduce drinking because alcoholism causes disability and contributes to suicide and accidents among young adults, said John Krystal, chairman of Yale University School of Medicine’s psychiatry department in New Haven, Connecticut, in an e-mail interview.
In the U.S., fewer than one in 10 overusers of alcohol gets treatment, the Bethesda, Maryland-based National Institute on Alcohol Abuse and Alcoholism, or NIAAA, estimates. Nine of 10 Germans and 19 of 20 U.K. residents who abuse alcohol don’t get help, according to the Geneva-based World Health Organization.
A Danish man whose first name is Niels -- and who asked that his surname be withheld to protect his privacy and prevent embarrassment to himself -- was consuming a bottle of vodka a day, leaving his house only to get more, when his doctor persuaded him to quit drinking six years ago, he said.
Now 66, the former advertising executive said he takes Antabuse. The drug, known generically as disulfiram, reacts with alcohol to induce vomiting in abstainers who backslide and take a drink. His memories of alcohol’s effects remain vivid: waking up sweating and shaking, craving a drink, he said. He wishes he could have a single glass of wine and be able to stop there, he said in an interview.
Antabuse isn’t the only current treatment for alcohol abusers. Acamprosate, the active ingredient in New York-based Forest Laboratories Inc.’s Campral, appears to reduce the symptoms, such as anxiety and insomnia, which abstinence from alcohol can trigger. Campral won approval in France in 1987, before the European Medicines Agency was created in 1995, and U.S. clearance in 2004.
While the experimental nalmefene works similarly to naltrexone, it fits better on cells and lasts longer, said Antero Kallio, chief medical officer of Biotie Therapies Corp., in Turku, Finland. That company licensed the drug to Lundbeck in 2006, having been unable to pay for all of the clinical trials needed to seek regulatory clearance.
Lundbeck agreed to pay Biotie as much as 88 million euros ($115 million) if nalmefene meets development and sales goals.
In a 28-week study, Finnish men and women taking nalmefene cut the number of days on which they drank heavily by as much as 45 percent, to as low as 8.6 days a month, researchers from Biotie and the A-Clinic Foundation, a government-funded treatment provider based in Helsinki, reported in 2007 in the journal Alcoholism: Clinical & Experimental Research. Patients getting a placebo cut heavy-drinking days by about one-third, showing an advantage for nalmefene.
‘Little by Little’
“Little by little, it decreases the craving for alcohol, and the person learns to control the alcohol problem,” said Hannu Alho, the independent coordinator of Lundbeck’s trials in Finland and the president-elect of the Calgary-based International Society of Addiction Medicine, a group of addiction specialists. “It’s a very much needed medicine.”
Lundbeck expects results as early as this month from trials of the drug in 1,850 people. Doctors would prescribe the pill on an as-needed basis. Patients who are worried about drinking too much could take it before their first glass, Lundbeck said.
“We’re not talking about the people on the bench in the park,” Anders Gersel Pedersen, executive vice president of drug development, said in an interview at Lundbeck’s headquarters in Valby, a district of Copenhagen. “We’re talking perhaps about people working in this building here.”
Lundbeck plans to seek European approval for nalmefene in 2011, and is in talks with potential partners who could market the medicine, Chief Executive Officer Ulf Wiinberg said Nov. 3.
Andreas Eggert, 42, is joining Lundbeck as vice president of global product strategy to oversee the introduction of nalmefene and the antidepressant LUAA21004, the company said today in a statement on its website. Nalmefene will reach the market in 2012, and LUAA21004 in 2013, Lundbeck said.
Rival treatments in development include Indianapolis-based Eli Lilly & Co.’s LY2196044, and topiramate, a product that New Brunswick, New Jersey-based Johnson & Johnson, among others, is testing.
Lilly completed a 16-week study of LY2196044, part of the second of three stages of human testing needed for regulatory approval, according to a U.S. government website that tracks clinical trials. Lilly for competitive reasons hasn’t disclosed how the compound works, according to the company’s website.
Topiramate is the active ingredient in Topamax, which J&J sells as an anticonvulsant. Researchers say the medicine, which is approved to prevent seizures and migraine headaches, may help balance electrical activity in the brain. Vivus Inc. in Mountain View, California, is seeking U.S. approval of a diet pill called Qnexa that combines topiramate with phentermine.
Desitin, a closely held company in Hamburg, began selling a naltrexone-based product called Adepend in September.
Lundbeck can’t prevent people who have quit alcohol consumption from using nalmefene to resume drinking, said Mads Kronborg, a company spokesman. The pill isn’t being developed for that purpose, he said in a telephone interview.
A 2006 report by the U.K.’s NICE said finding treatment funding, either private or public, “has proved difficult.” While most U.S. states require health insurers to at least offer treatment, federal law may exempt larger employers, NIAAA said in its five-year strategic plan.
“Every physician knows that alcohol is bad for all parts of your body,” said Christian Haasen, a professor at the University of Hamburg’s Center for Interdisciplinary Addiction Research, who is also an independent investigator in Lundbeck’s nalmefene trials. Doctors will be “quite interested” in the Lundbeck drug, he said.
For now, it’s an open question that the product will work, the Waggoner Center’s Harris said.
“The controversy is whether recovering alcoholics can maintain moderate consumption without returning to harmful drinking,” Harris said.