Phase 3 trials test the efficacy and safety of a new drug in human patients.
In one phase 3 trial, patients with primary progressive MS who were given the experimental drug ocrelizumab had less medical evidence and brain scan evidence of disease progress compared to patients given a placebo.
And in two other, separate phase 3 trials, patients with relapsing forms of MS who were given ocrelizumab showed lower rates of disease activity and progression compared to patients receiving Interferon beta 1a, a standard MS treatment.
The researchers caution that extended observation is required to determine the long-term safety and efficacy of the drug.
Ocrelizumab is under review
by the Food and Drug Administration for approval for both primary progressive and relapsing MS. For the primary progressive multiple sclerosis indication, the FDA has given Breakthrough Designation and priority review, in order to move up the time line for potential approval.
The FDA does not comment on drugs that are under review. Still, the reason for an expedited approval process seems obvious. It is needed.
"No treatments have been approved by the FDA for primary progressive MS," said Dr. Jack Burks, chief medical consultant for the Multiple Sclerosis Association of America
. He said only about 10% of the MS population is estimated to be diagnosed with the primary progressive form of MS, but "this still represents tens of thousands of individuals who currently have no available treatment options."
How it works
Ocrelizumab selectively targets CD20-positive B cells, a type of immune cell. B cells are thought to be a key contributor to myelin (nerve cell insulation) and nerve cell damage, which can result in disability for patients with MS, said Dr. Peter Chin, group medical director for neuroscience at Genentech
, the company that makes the drug.
"B cells have been targeted in other disease states with other drugs (notably Genentech's Rituxan, which has been used to treat certain blood cancers and rheumatoid arthritis)," said Chin in an email. Because Ocrelizumab attacks only B cells, other cells may remain unharmed and important functions of the immune system may be preserved.
According to Chin, ocrelizumab is new because it is the first B cell targeting therapy that has had an impact on both relapsing and primary progressive MS and it is important because it is the first and only therapy that has an impact in primary progressive MS.
There are 14 therapies available to treat the relapsing forms of MS, noted Burks.
During the clinical trial for patients with primary progressive MS, 488 patients were randomly assigned to receive ocrelizumab while 244 received placebo. On average, patients remained in the study for nearly three years.
Overall, the rates of adverse events did not differ significantly between the two groups. At 12 weeks, 32.9% of the ocrelizumab group patients had confirmed disability progression versus 39.3% with placebo. At 24 weeks, 29.6% of the ocrelizumab patients had confirmed disability progression compared to 35.7% with placebo.
In clinical trials for patients with relapsing forms of MS, the annual relapse rates were lower for patients taking ocrelizumab than patients taking interferon beta-1a.
"In addition to slowing disease activity for individuals with primary progressive MS -- which includes reduction in the progression of clinical disability as well as a reduction in brain-lesion activity -- data for ocrelizumab has shown to be highly effective for people with relapsing MS," said Burks, who explained the drug reduced the frequency of relapses in relapsing MS, along with decreasing progression of disability and brain-lesion activity when compared to another established treatment.
Burks said the side-effects also appear to be reasonable compared to other highly effective drugs: "The potential is very exciting."