Two MS Pills Show Promise
Novartis, Merck drugs—effective in trials—could be boon for patients
JANUARY 21, 2010
By JEANNE WHALEN [WSJ]
Two experimental pills for multiple sclerosis proved effective in clinical trials, raising the possibility for the first time that oral treatments might become available alongside the more cumbersome injections and infusions used to treat MS today.
Some patients taking the drugs—made by Switzerland's Novartis AG and Germany's Merck KGaA—experienced adverse events that researchers said need to be carefully weighed against the drugs' benefits. The adverse events included herpes infections, a small number of cancer cases and a type of eye disease that can lead to blindness, according to the results of the clinical trials, which were published Wednesday by the New England Journal of Medicine.
Regulators including the U.S. Food and Drug Administration are deciding whether to approve the drugs for sale.
Oral drugs would mark a notable advancement in MS treatment. The main treatments used today—Copaxone or a group of drugs called interferons—usually need to be injected several times a week, which many patients find burdensome. The drugs are moderately effective in some patients and have few side effects but don't work well in everyone.
A more potent drug called Tysabri is given by monthly infusion, and works well in many patients, but is associated with a serious side effect—a rare but potentially lethal brain infection.
"MS is still an area where there are few options, so we have to be grateful for any entering the arena," said Mike Boggild, a neurologist who treats MS patients at the Walton Centre in Liverpool, England. "An oral agent is something patients have been asking for for many years."
An oral drug that won favor with doctors and patients could have significant commercial potential, possibly generating annual sales of $1 billion or more, analysts have said.
In MS, the body's immune system attacks nerve cells in the brain, which can lead to tingling, muscle weakness and, in severe cases, paralysis and loss of vision. People with the most common form of the disease—relapsing-remitting MS—experience attacks, or relapses, followed by periods of remission.
The New England Journal of Medicine on Wednesday published results of three studies of the oral drugs, known by the generic names fingolimod and cladribine. The studies were financed by the drug makers.
Fingolimod, made by Novartis, was tested against a placebo pill in one study and against an interferon called Avonex, in another. In both studies, patients taking fingolimod had a significantly lower risk of suffering a relapse. When compared with the placebo, fingolimod patients had a lower risk of their disability worsening, though this risk was roughly even when fingolimod was compared with Avonex. Doctors have said Avonex is generally considered to be the weakest interferon.
In a third study, patients taking Merck's cladribine also had a significantly lower risk of relapse compared with patients taking a placebo and a lower risk of worsening disability.
Patients taking both oral drugs experienced higher rates of herpes infections. Two patients who got the infections while taking a high dose of fingolimod died. In one trial, basal-cell carcinoma, melanoma and breast cancer were more common in patients taking fingolimod than in those taking Avonex, though this wasn't the case in the trial comparing fingolimod with a placebo.
In the cladribine trial, tumors were reported in 1.1% of patients taking the drug versus none on a placebo. Researchers leading the trial called these a "small number" of cases that didn't "establish a risk for the use of cladribine."
Other side effects in patients taking fingolimod included abnormally slow heart rate, hypertension, elevated liver-enzyme levels and an eye disease called macular edema.
Moses Rodriguez, a neurologist and director of the MS Center at Mayo Clinic in Rochester, Minn., said he wasn't particularly impressed by the efficacy data and was concerned about the side effects. In terms of efficacy, "my feeling is, these drugs will be similar to the interferons," he said, with a side-effect profile that is "a lot worse."
The National Multiple Sclerosis Society called the side effects "manageable" but said they should be closely monitored over the long term.
Write to Jeanne Whalen at jeanne.whalen@wsj.com |
