Is Idebenone Worth Waiting For?

The word is out about idebenone. It's shown encouraging effects against Friedreich's ataxia in clinical trials in France, and for those who want it and are willing to pay, it's available in the United States. But from the standpoint of U.S. researchers and health officials, the French results fall short of proving that the drug is safe and effective for FA.

When their son Keith Andrus experienced a sudden decline in cardiac function, Ron and Raychel Bartek decided he should start taking idebenone.

That leaves families with FA in a quandary. Should they wait for the completion of the U.S. idebenone trial at NIH, or should they trust the French trials and start using idebenone now?

Trials…

The French trials, led by Pierre Rustin and Arnold Munnich at the Hospital for Sick Children in Paris, have made idebenone a popular and accepted treatment for FA in France.

"Idebenone is covered by the [French] social security system, and FA patients can get it by a somewhat tedious

"I think that there is a general agreement, not only from the published work of Munnich and Rustin but also from personal communications with others, that idebenone has some beneficial effect on the hypertrophic cardiomyopathy [heart enlargement] in FA. The other point is that idebenone is known to be a safe drug. For these two reasons, we believe in France that idebenone therapy is warranted for FA," Koenig says.

But the French trials didn't meet the standards of the U.S. Food and Drug Administration (FDA), and therefore, idebenone hasn't been approved for treating FA in this country.

Rob Wilson, a lead investigator in the NIH idebenone trial, says the FDA has good reasons for being cautious about the drug. One is that the French trials didn't compare idebenone to a placebo (an inert substance not expected to have a therapeutic effect), and another is that the results showed only that idebenone shrank the enlarged hearts of people with FA. That's not enough to prove that idebenone can enhance heart function, Wilson says.

"We can't rule out the alternative hypothesis that the drug is somehow shrinking the heart for some other reason," he says. "To grant an indication for a drug, the FDA needs more than that. They need something that is truly meaningful for patients' lives."

Assessments of cardiac function usually require exercise tests, like stair climbing or jogging, that would be impossible for many people with FA, Wilson says. So, in the NIH trial, he and collaborator Kenneth Fischbeck hope to show that idebenone (at much larger doses than previously tested) can alleviate ataxia or improve overall well-being in FA.

…And Tribulations

A Japanese company, Takeda Chemical Industries, holds the patent on idebenone and has sold limited amounts of it to retailers of vitamins and dietary supplements. That means it's available to Americans with FA (mostly via the Internet). But is it effective? Is it even safe?

"It's a tough choice," Wilson says. "The evidence is suggestive, but there's no proof that it helps. Plus there could be some long-term toxicity that we don't know about."

Pat Kiernan, whose 13-year-old daughter Erin has FA, echoes Wilson's concerns. "This is a very difficult thing for a parent," he says. "My perspective is that without [idebenone], she's not going to live a very long life. On the other hand, we want to make sure that we're not poisoning her."

Kiernan and his wife, Karen, plan to at least wait for preliminary results from the NIH trial; other families with FA are already using idebenone.

Ron and Raychel Bartek, whose 16-year-old son Keith Andrus has FA, are supportive of the NIH trial, and since they live in Annandale, Va. (not far from NIH), they've registered Keith to participate. "We have great regard for the preliminary [French] trials, but we also want to know the effect of larger doses and whether they affect symptoms in addition to the heart," Ron says.

Like the Kiernans, the Barteks were planning to wait for the trial's completion before making a decision about idebenone. But recently, Keith began having serious

Kenneth Fischbeck

"We've agonized for several months about what to do," Raychel says. "The change happened almost overnight. [Keith] was fine when he saw the cardiologist in November, but in February he started complaining that his heart felt like it was racing. It turned out he had an arrhythmia and a dramatic drop in cardiac function."

The Barteks have informed Keith's cardiologist about their choice and continue to take Keith in for regular checkups, hoping they'll see a measurable improvement in his condition.

More Uncertainties

By the way, idebenone is expensive (the Barteks are paying nearly $250 a month), and unless the FDA approves it for FA treatment, families can't get insurance coverage for it.

In fact, if it doesn't get FDA approval, retailers may run out of the Takeda product. Originally, idebenone was developed as a treatment for stroke, but when the drug didn't work for stroke patients, Takeda stopped making it. The company sees little to gain in marketing it for a rare disease like FA.

Fortunately, Wilson and Fischbeck were able to work with FDA officials and persuade Takeda to provide enough idebenone for the NIH trial. They hope the trial will show that idebenone works against FA, and that Takeda will license the drug to a smaller company.

In the meantime, Wilson says, "I tell parents, 'If your kid has overt cardiomyopathy and you're terribly worried about it, put your kid on idebenone.'"

Fischbeck is more cautious. "I don't recommend people getting the drug over the Internet or from other sources," he says. "When you get drugs from abroad, you don't get the same guarantees that they're effective and safe. Give us the time to show that idebenone is safe, and to show that it works over a long period. We're pushing [the trial] as fast as we can."