SAN FRANCISCO – Bay Area researchers released successful clinical trial results Thursday for a promising new drug that could become the first to treat a devastating progressive form of multiple sclerosis.
The findings of late-phase trials found that the drug, called ocrelizumab, greatly reduced symptoms for progressive multiple sclerosis as well as a more common form of the disease, known as relapsing and remitting multiple sclerosis, which strikes about 85 percent of MS patients.
Treatments exist for the relapsing and remitting form, which is characterized by periodic flareups followed by partial or complete recovery, but no drug has been approved to treat the kind that worsens after diagnosis.
“The results are dramatic,” said UCSF neurologist Stephen Hauser, who has been studying multiple sclerosis for 35 years and presented the findings at a meeting of the European Committee for Treatment and Research in Multiple Sclerosis in Barcelona. “It’s the first time there has been a drug proven to work for people with progressive MS.”
The drug’s manufacturer, South San Francisco’s Genentech, plans to apply early next year to the U.S. Food and Drug Administration for approval of the drug to treat both forms of the disease.
The studies involved two trials for relapsing MS that included more than 1,600 patients and one that tested the drug on more than 700 patients with the progressive disease.
“The results of these three pivotal trials have the potential to transform the treatment of MS,” said Dr. Sandra Horning, Genetech’s chief medical officer and head of global product development, in a release announcing Thursday’s results.
More than 400,000 Americans and 2.5 million people worldwide are living with multiple sclerosis, an unpredictable and mysterious autoimmune disease that involves the central nervous system.
In people who have the disease, the body’s immune system attacks the insulation, or myelin, around nerve cells that carry electric charges needed to communicate with other nerve cells.
When that communication is disrupted, the nerve cells can die or be damaged, causing a wide variety of symptoms in patients, from pain or numbness, typically in the arms and legs, to blindness and severe muscle weakness.
Among its many mysterious properties, MS symptoms vary greatly from patient to patient, becoming a minor inconvenience to some people and a debilitating condition to others, leaving them immobile.
While about 85 percent of MS patients are initially diagnosed with the relapsing and remitting form, 10 to 15 percent are diagnosed with the progressive form. Every year, about 2 percent of patients with the relapsing kind transition to the progressive form.
When UCSF’s Hauser began researching the disease, the prevailing theory among researchers was that the immune system’s T cells were behind the autoimmune reaction. While clearly important to the process, Hauser discovered T cells were not the “smoking gun,” and another theory emerged, this one involving another immune cell, the B cell.
But the medical establishment, Hauser said, was so firmly entrenched in the T cell theory that he couldn’t get federal funding to support B cell research. He turned to Genentech, which had already developed, and received FDA approval for, the first antibody designed to target the B cell.
The drug, Rituxan, was approved to treat lymphoma, but Hauser and his colleagues used it experimentally on MS patients. He said the results on MS patients were remarkable and immediate.
“This pivoted the entire field,” said Hauser, who said he has no financial interest in the drug. “First, it validated the concept and changed the field … and then it sent us back to the lab with laser-like focus.”
In trial results revealed Thursday involving the relapsing multiple sclerosis patients, the researchers tested ocrelizumab against Rebif, which is considered highly effective and is one of 13 drugs approved to treat relapsing MS patients. Ocrelizumab was found to reduce attacks by nearly half over the two-year study period and showed fewer side effects, compared with Rebif.
Results of the separate study of patients with the progressive form of MS won’t be released until Saturday, but Hauser said they are equally promising.
Even though patients with relapsing disease have treatment options, Hauser said they need options that are more effective and better tolerated. “The community now believes, for many people with MS, more highly effective therapies earlier in the disease is likely to be very helpful over the long run,” he said.
MS patients and their advocates welcomed Thursday’s announcement, especially for those with the progressive form who currently are limited to drugs that reduce symptoms but don’t address the mechanisms of the disease.
San Francisco landscape architect Sarah Warto, who was diagnosed with the relapsing form of the disease in 2004, hopes the results will help her continue to stave off symptoms and avoid the type of disabilities she has observed in fellow patients.
Warto had been taking Rebif but recently shifted to a new drug after the birth of her first child triggered a significant flareup, her first relapse in about seven years. Her concern is that her symptoms, which continue to plague her, will worsen if and when she has a second child.
“It’s the most promising I’ve felt in a very long time,” she said of the potential of the new drug. “This is the first time I’ve had a real option I think is valid enough to change the decisions I make in my life.”
Bruce Bebo, executive vice president of research for the National Multiple Sclerosis Society, said he looks forward to seeing the detailed safety and effectiveness results from the trials.
“This has the potential to be a major advance for people living with primary progressive MS who have waited so long for an effective disease-modifying therapy,” he said in a statement before Thursday’s results were released.
