02/13/2012 0 Comments Contact Our News Editors

By Amy Marcus

A drug used to treat multiple sclerosis has also been shown to slow the progression of Lou Gehrig's disease in mice, a nonprofit biotechnology company plans to announce Tuesday. Now, scientists face a dilemma.

Amy Dockser Marcus on Lunch Break discusses the growing trend of studying existing drugs for use in other illnesses and why it's hard to get patients into clinical trials for drugs already on the market.

Many patients with Lou Gehrig's disease, a fatal disorder formally known as amyotrophic lateral sclerosis, may want to try the drug on their own—even though there's no evidence that it is safe or effective in patients with the disease.

But scientists want patients to enroll in a clinical trial, one that specifically examines how the drug, Gilenya, works in people with ALS. They hope to launch that trial later this year.

"We want to make sure we are not doing any harm. We want to do the trials correctly and quickly," said Steven Perrin, president and chief executive officer of the ALS Therapy Development Institute, a Cambridge, Mass.-based group that is releasing preliminary findings on Gilenya.

Still, Dr. Perrin acknowledged the difficulty in asking ALS patients to hold off while a clinical trial is conducted on a drug that could potentially ease their condition. When it comes to developing therapies for the disease, "for ALS patients, yesterday is not fast enough," Dr. Perrin said.

This research dilemma is occurring with increasing frequency, as scientists and public-health officials look to already approved medicines to see if they can treat other illnesses.

Last week, a paper in the journal Science showed that skin-cancer drug bexarotene improved brain function in mice bred with Alzheimer's disease. Following publication, Alzheimer's patients asked their doctors to prescribe the drug off-label before researchers even launched a trial in people.

Doctors are allowed to prescribe approved medications off-label when they believe the patient may benefit, but many are reluctant because the drug may prove to be toxic in a different condition.

There are many reasons why patients seek a drug off-label. Designing clinical trials and getting them approved by hospitals and the Food and Drug Administration takes time, and patients with deadly diseases often feel they cannot wait. Drug trials often cannot accept very ill patients, who often feel they have little to lose if they take the drug off-label. Most important, many patients object to the possibility of getting a placebo, which helps researchers determine if a drug is really working.

Merit Cudkowicz, the co-principal investigator on the planned Gilenya trial in ALS, cited a previous effort to test a promising ALS drug. Published studies indicated that a widely used antibiotic, minocycline, appeared to slow disease progression in mice. But it took several years to enroll enough patients in a trial because so many people started taking the drug off-label, Dr. Cudkowicz said. In the end, the trial showed not only that minocycline didn't work in ALS, but that it accelerated the illness. "If we knew the drug worked, we wouldn't need the trial," said Dr. Cudkowicz, professor of neurology at Massachusetts General Hospital and Harvard Medical School.

She said that Massachusetts General has started bringing in patients and their families to explain the importance of enrolling in a trial. They're also emphasizing the need for a placebo group in order to compare the drug's impact on patients' functional change and survival. But in response to patients' concerns, ALS doctors are trying to find ways to shorten the length of time on a placebo, and they sometimes promise that if the drug works, all patients in the trial will have access to the compound at a later stage.

Christopher Austin, scientific director of the National Institutes of Health Center for Translational Therapeutics, which is running clinical trials of already approved drugs in different diseases, said patients taking drugs off-label can also raise ethical questions.

Many insurers won't cover the costs of a drug taken off-label. Some drugs, including Gilenya, are very expensive, so that only wealthier patients can afford to pay for a drug out-of-pocket. "That is not an ideal situation," Dr. Austin said, since it raises equity issues. A spokeswoman for Novartis, the drug's maker, said that the cost of Gilenya runs approximately $52,365 annually.

Trying approved drugs in new indications raises complicated questions for companies, too. A drug maker may not be interested in pursuing new trials, and serious adverse events may also draw regulatory attention. There are expenses as well. The ALS institute would like Novartis to cover the cost of Gilenya in the planned trial, something the company has not yet agreed to do.

"It's hard to do good quality research, and bad research hurts everyone. No matter what the companies do, someone will be upset," said Jamie Heywood, chairman of PatientsLikeMe, a closely held health-data sharing company in Cambridge, Mass. When ALS patients on the company's site shared data about off-label use of the drug lithium, the company analyzed the results and published findings in Nature Biotechnology last year.

A spokeswoman for Novartis said in a written statement that the company is committed to working with the ALS institute about a planned trial of Gilenya in ALS p