Experimental Pill for Multiple Sclerosis Shows Promise
MONDAY April 16, 2012 -- An experimental pill reduced the number of lesions in the brains of people with multiple sclerosis (MS), researchers report.
The drug, which currently goes by the name ONO-4641, "actually caused a reduction in relapses, which is somewhat unusual in a study this small and is quite encouraging," said lead researcher Dr. Timothy Vollmer, a professor of neurology and medical director of the Rocky Mountain MS Center, located at the University of Colorado, in Denver.
The medication is also "more selective than other drugs in its class and hopefully that will provide a better safety profile long-term," Vollmer said. He added that the aim of the therapy is to prevent MS-linked disability and prevent brain damage.
"We are shifting our therapeutic goals. We are no longer interested in just slowing the disease, we are actually interested in putting patients into what we call a 'disease activity-free' state," he explained.
"And in some patients, with these highly effective therapies, our goal is to induce a remission of symptoms and that's doable in patients with early disease. The goal is going to treat early and aggressively to prevent brain injury," Vollmer said.
The results of the phase 2 clinical trial were released April 16 and will also be presented next week at the American Academy of Neurology's annual meeting in New Orleans.
Commenting on the study, Dr. Gary Birnbaum, director of the Multiple Sclerosis Treatment and Research Center at the Minneapolis Clinic of Neurology, said that ONO-4641,"appears to be similar in mechanism of action to the approved drug, fingolimod (Gilenya), but appears to be more selective in its action."
Nevertheless, based on the recent post-marketing reports of sudden death in patients on fingolimod, and the data reported in this trial of slowed heart rate in patients receiving ONO-4641, similar safety concerns may arise with this drug, Birnbaum said.
"In addition, the drug induces a lymphopenia [low white blood cell count], indicating it too is an immune suppressant. Immune suppression has its own dangers, as noted with fingolimod, where two patients died of liver infections, and there was an increased risk of skin cancer," Birnbaum said.
More study is needed to assess the long-term effectiveness and safety of ONO-4641, he said.
"At first glance, the drug appears to reduce central nervous system inflammation, but data on reducing [MS] disease progression and long-term safety will be needed to assess the final value of this drug," Birnbaum said.
For the trial, investigators randomly assigned 407 people aged 18 to 55 with relapsing-remitting MS to one of three daily doses of the drug or placebo. Patients underwent brain scans once every month between weeks 10 and 26 of treatment.
After 26 weeks, Vollmer's group found that compared to those taking a placebo, patients on the low dose of ONO-4641 experienced an average 82 percent reduction in what experts call "MS-enhancing brain lesions."
For those receiving the middle dose the reduction was 92 percent and for those on the high dose, 77 percent, they found.
Adverse events were related to the dose of the drug patients received and included cardiovascular events such as a slower heartbeat, blood pressure changes or other heart problems.
Other side effects included liver-enzyme elevations. In addition, lymphopenia occurred in 4 percent of people receiving the high dose of ONO-4641 and in 1 percent of those receiving the middle dose, the researchers note.
The study was supported by the drug's maker, Ono Pharmaceutical Co., Ltd.
Another expert, Nicholas LaRocca, vice president for health care delivery and policy research at the National MS Society, said that "MS is a complex disease that affects each person differently and so it is important for people with MS to have access to a variety of options for safe and effective therapies."
"Based on this phase 2 study, ONO-4641 appears promising and so we look forward to the results of larger studies of this new agent," he said.
Findings presented at medical meetings are typically considered preliminary until published in a peer-reviewed journal.
To learn more about MS, visit the National Multiple Sclerosis Society.
Posted: April 2012