Fat-fighting drugs may be a far riskier business than they seem

Experts are warning that despite the fact that obesity is one of the biggest preventable causes of death, fat-fighting drugs may be a far riskier business than they seem, particularly for investors.

Arena Pharmaceuticals has announced that its new experimental drug APD356 has enabled patients to shed an average of 2.9 pounds in only 28 days. However the limited duration of the study may mean safety issues have not been addressed.

Arena's new pill originates from one of the drug industry's biggest disasters, the diet combo fen-phen, a combination of fenfluramine and phentermine, which damaged the heart valves of some of the people who took it. Fenfluramine was withdrawn from the market, and resulted in massive legal costs for drugmaker Wyeth which has now had to reserve some $21 billion to pay for legal settlements related to the drug. Some analysts expect that number could be greater.

Fenfluramine worked by increasing the amount of serotonin in the brain in a way that reduced appetite, and Arena explains that fen-phen hit more brain receptors than was necessary.

Apparently APD356 is far more specific, and so far the heart valve damage that led to fen-phen's withdrawal has not been repeated.

According to Jack Lief, Arena's chief executive, the heart valve side effects with Fenfluramine were rare, and a big clinical trial could settle the issue. He says the current trial is too small to lead to definite conclusions, and to finish developing the drug, and Arena may need to enlist a big pharmaceutical partner.

The field of anti-obesity medicines has an array of failures and disappointments. Fen-phen was effective but proved deadly, many doctors saying it was overused on patients whose obesity was cosmetic and not a health risk. Meridia, from Abbott Laboratories, and Xenical, from Roche, have both failed to succeed, partly because of side effects.

Steven Nissen, a cardiologist at the Cleveland Clinic who is working on another obesity drug Acomplia from Sanofi-Aventis, says the news from Arena is promising but also 'scary'.

Sanofi's new effort, Acomplia, which will be submitted for approval to the FDA this year, is the exception that proves the rule. The drug blocks the same receptors that gives pot smokers the appetite, and could help overweight patients lose weight. It may also be used to make it easier for tobacco smokers to quit smoking.

Some analysts predict annual sales of $5 billion or more for Acomplia, and the reason for the optimism is that the same cannabinoid (from cannabis or marijuana) receptors that reduce cravings, are also present in fat cells.

Along with helping heavy patients lose weight , Acomplia also raises good cholesterol, cuts bad cholesterol, reduces triglycerides and generally seems as if it should reduce the risk of heart disease and other obesity-related killers.

The trial aims at proving that the drug will reduce the amount of plaque that builds up in arteries. Acomplia's potential is to be a chronic medicine on a par with Pfizer's cholesterol-lowering medicine Lipitor, the world's top seller.

Bristol-Myers Squibb also recently licensed its own Acomplia-like drug, which is in early safety trials.

An appetite-reducing drug that works in the brain probably doesn't have the same potential and even if Arena's pill clears all safety hurdles, investors might need to exercise caution. But Arena, a small company, does have some other irons in the fire, including a couple of experimental drugs, one of which is a sleeping pill.

Arena also recently signed a deal with the potential worth $317 million with Johnson & Johnson to develop diabetes medicines. Lief says it is the biggest such deal ever in biotech.