April 30, 2009 (Seattle) -- Two new oral drugs cut by about half the relapse rate in people with multiple sclerosis (MS).
If approved by the FDA, the drugs -- cladribine and fingolimod -- would become the first treatments for MS that don't involve regular injections or infusions.
In a second study, 80% to 84% of MS patients taking the immune-suppressing drug fingolimod were relapse-free after one year of daily treatment, compared with 67% of those taking the standard injectable MS drug Avonex.
Either drug will meet a huge unmet need as "a lot of patients refuse to go on treatment right now because it involves injections," says Lily Jung, MD, medical director of the neurology clinic at the Swedish Neurology Institute in Seattle. Jung was not involved in either study.
Both studies were presented at the annual meeting of the American Academy of Neurology.
Cladribine Fights Multiple Sclerosis
Cladribine, already licensed for treating leukemia under the brand name Leustatin, suppresses the autoimmune responses thought to cause MS. In MS, T cells -- the "generals" of the immune system -- go haywire and order attacks on the myelin sheaths that surround and protect the brain cells.
"Cladribine damages the ability of the T cells to reproduce and proliferate," Jung says.
The new phase III study involved about 1,200 patients with the relapsing form of multiple sclerosis, characterized by repeated relapses with periods of recovery in between. They suffered from the disease for an average of six to seven years, and all had at least one relapse in the year before entering the study.
Patients were given either four courses of low-dose cladribine tablets or six courses of higher-dose cladribine tablets, or a placebo.
Each course consisted of one to two tablets per day for four or five days, "meaning that individuals with MS only have to take tablets for eight to 20 days a year," says Gavin Giovannoni, MD, of the Barts and London School of Medicine and Dentistry, which led the study.
That should improve compliance, he says.
The patients were followed up for nearly two years and monitored using MRI scans.
Cladribine Cuts Relapse Rate
Compared with patients who were taking a placebo, those taking cladribine were 55% to 58% less likely to suffer a relapse in a year and 33% less likely to suffer worsening in their disability, such as having more trouble walking.
MRI scans showed that patients taking cladribine also had significantly fewer lesions in the deep parts of the brain or spinal cord that are characteristic of MS.
"These results are really exciting," Giovannoni tells WebMD. "They have the potential to make a big difference in the lives of patients with MS."
Manufacturer Merck Serono, which funded the study, says it plans to seek FDA approval in the coming months.
Fingolimod Fights MS
Fingolimod also suppresses the autoimmune responses thought to cause MS, but in a different way. It's a molecule that locks T cells inside the lymph nodes, so they can't float around in the bloodstream and make their way to the brain and spinal cord. It was originally designed to help prevent organ rejection in kidney transplant patients, but that didn't work out very well, Jung says.
In that phase III study, more than 1,200 patients with the relapsing form of MS received one of two doses of fingolimod or Avonex daily for one year.
They suffered from the disease for an average of seven years, and all had an average of two relapses in the two years before entering the study.
Compared with patients who were taking Avonex, those taking fingolimod were 38% to 52% less likely to suffer a relapse in a year. They also had fewer new lesions and fewer lesions overall than those on the injectable drug.
The study wasn't long enough to show an effect on disability, says study head Jeffrey Cohen, MD, of the Cleveland Clinic.
The most common side effects were head colds, headache, and fatigue. But there were also eight cases of skin cancer and four cases of breast cancer. It is unclear whether the drug was responsible for the events.
Jung again cautions that longer-term data are needed. Fingolimod is a potent inhibitor of immune responses and patients are being watched carefully, she notes.
Two other large studies of fingolimod are still ongoing, with results expected later this year. Drugmaker Novartis, which funded the current trial, hopes to apply for FDA approval by the end of 2009.