A long-term study of the drug Gilenya shows the medication to be consistently effective in treating multiple sclerosis (MS) without any new side effects.
The phase 3 TRANSFORMS study began enrolling patients in May 2006, meaning that some patients have potentially been on the drug for nearly a decade.
Gilenya, also know by its scientific name of fingolimod, is the first-ever pill form of treatment for MS. The Novartis drug has been on the market since late 2010.
According to the study’s co-author, Dr. Jeffrey Cohen, director of the Mellen MS Center at the Cleveland Clinic, there were no surprises from these long-term findings.
“[The results] were very reassuring,” Cohen told Healthline. “We are now, on average, four or more years on follow-up with over 1,600 people and there didn’t appear to be an increase in side effects or safety issues over time. There didn’t appear to be new adverse effects emerging and lymphocyte count didn’t appear to be going down.”
A Clever Design
The TRANSFORMS study was designed as a comparator trial, meaning there was no placebo.
Instead, the drug was compared to Avonex, at the time considered to be one of the most effective treatments for MS. One out of three participants would take Avonex while the other two would be randomly assigned to take one of two different doses of fingolimod.
But comparing an injection like Avonex to a pill and preventing patients from knowing which drug they were on presented a unique set of challenges.
Researchers decided to have participants take a shot once a week and a pill once a day. Either the shot or the pills would be fake and the patient would only be taking one real drug. So, for a year, participants in the TRANSFORMS study injected themselves weekly and took a daily capsule.
It’s difficult to design a blind study where two drugs with such different delivery methods are compared and some patients may have had a guess as to what they were on, said Cohen, “particularly if they had very prominent side effects typical of interferon.”
However, studies in MS comparing a new drug to an existing one are becoming the norm, according to Cohen.
He said it’s becoming more difficult, practically and ethically, to do lengthy studies with a placebo group because there are now so many effective treatments available for MS.
But there is still room for short term, phase 2 trials use MRI studies as they are “more efficient, and you can do the study much quicker, with fewer people if you have a placebo group,” he explained, “But I think phase 3 studies [with placebo groups] will become more and more uncommon.”
Karen Hertel, a homemaker and community volunteer from Eugene, Oregon, took part in both the core study and the long-term extension.
“I began the TRANSFORMS study May 7, 2007,” she explained in an interview with Healthline. “When I was unblinded, I was told that I had been on the [0.5] dose of fingolimod [since the beginning].”
Having previously been on Avonex before the study, Hertel pointed out that “I had to take two drugs to counteract the side effects [at the time]. When I didn't experience flu-like symptoms [after starting the TRANSFORMS trial], it was obvious to me that I was on Gilenya.”
Examining the Long-Term Effects
After the core study was completed, all participants were invited to continue in the extension phase of the study so that long-term monitoring could begin.
People originally assigned to the higher dose of fingolimod and those on Avonex would be switched over to the 0.5 mg arm. This was the dose that won final approval by the Food and Drug Administration (FDA).
As part of any drug testing, researchers experiment with doses to try and identify the smallest possible amount of a drug necessary to give the greatest benefit.
“The original phase 2 study [of fingolimod] actually looked at 5 mg and 1.25 mg and there didn’t seem to be any difference in [effectiveness],” Cohen explained, “but the 5 mg dose seemed to have more safety issues.”
The phase 3 studies used the 1.25 mg dose from the earlier trial and compared it to an even smaller 0.5 mg dose as well as Avonex.
“Again, … there did not appear to be any difference in benefit, but the 0.5 mg dose seemed to have fewer safety issues so that was the dose that was ultimately approved by the FDA and other regulatory agencies,” said Cohen.
More Studies Under Way
So are there any ongoing studies looking at an even lower dose?
According to Cohen, “Yes. That was one of the stipulations [made by the FDA] at time of approval that lower doses also be subsequently tested.”
Indeed, there is a currently enrolling study being conducted at 216 sites worldwide to test .25 mg and .5 mg against the effectiveness of Copaxone, another MS drug.
The long-term data continue to support the original findings that Gilenya is a highly effective disease-modifying therapy. But you don’t have to convince Hertel.
Although everyone’s experience is different, Hertel went from relapsing frequently before the trial — needing a cane and sometimes a wheelchair to get around — to only having two mild relapses since beginning the study.
“Now I can participate in so much more of life.”