BARCELONA -- An investigational agent targeting B-cells diminished relapses and disease progression over 2 years in relapsing-remitting MS compared with interferon therapy, according to results from the OPERA trials.
In the two phase III studies, patients taking the anti-CD20+ drug ocrelizumab had about a 50% reduction in annualized relapse rates compared with those taking interferon-beta 1a (Rebif) (P<0.0001 for both studies), according to , of the University of California San Francisco, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- In two randomized, controlled studies, OPERA I and II, the investigational anti-CD20+ drug ocrelizumab administered as a 600mg IV infusion every 24 weeks reduced annualized relapse rate in RRMS patients by approximately 50% compared with high dose interferon, and additionally reduced disease progression by approximately 40%.
- Ocrelizumab was well tolerated and rates of serious adverse events in the ocrelizumab arm were low and similar to those seen in the interferon arm.
Patients on the novel drug also had about a 40% reduction in progression that was sustained for both 12 and 24 weeks compared with those on interferon in pooled analyses, the researchers reported here at the .
"These trials demonstrate that targeting CD20+ B cells with ocrelizumab is potentially a highly effective and well tolerated approach for patients with relapsing-remitting MS," Hauser said during the presentation.
Drugmaker Roche/Genentech also reported positive results for the monoclonal antibody in primary progressive MS evaluated in the ORATORIO study at the meeting.
Ocrelizumab is not the first anti-CD20+ monoclonal antibody tested in progressive as well as relapsing-remitting MS. The pioneering drug in this class, rituximab (Rituxan), has also been tested in both progressive and relapsing-remitting MS and showed promise, but Roche/Genentech chose not to fund further trials.
The new drug is a fully humanized monoclonal antibody, whereas rituximab is chimeric, and it binds more tightly to its target than the older drug.
For the OPERA studies, researchers randomized 1,656 patients with relapsing-remitting MS to a 600-mg IV infusion of ocrelizumab every 6 months or to interferon beta-1a (Rebif) given as 44-mg subcutaneous injections three times per week.
They found that the investigational agent reduced the annualized relapse rate by about 50% over 2 years compared with interferon (0.292 versus 0.156 in OPERA I and 0.290 versus 0.155 in OPERA II, P<0.0001 for both studies).
The investigational drug also slowed progression as measured by EDSS scores by a relative 40% sustained for both 12 and 24 weeks compared with interferon in both studies: 15% versus 9.8% with progression after 12 weeks (P=0.0006) and 12% versus 7.6% with progression after 24 weeks (P=0.0025).
Ocrelizumab-treated patients also had significant reductions in the number of T1-gadolinium-enhancing lesions at 24, 48, and 96 weeks compared with those on interferon (by about 90% between groups), as well as about an 80% reduction in T2 hyperintense lesions at all those time points compared with interferon.
In exploratory analyses, the researchers found a reduction in the rate of brain volume loss as well as a significant improvement in No Evidence of Disease Activity (NEDA) scores for those on ocrelizumab compared with those on interferon.
Overall adverse events were similar in both groups in both trials at about 83%, but as expected, infusion-related reactions were higher in the ocrelizumab group (34.3% versus 9.7%). There were similar rates of serious adverse events including serious infections (6.9% and 8.7%), and there were no cases of progressive multifocal leukoencephalopathy (PML), Wolinsky said.
Many experts interviewed by ľֱ noted that 2-year data may be insufficient to detect all of the potential safety issues with the drug.
after seeing an increased risk of serious and opportunistic infections, some of which were fatal. Patients in the MS population, however, may be getting a different dose of the drug and may be younger and healthier than those in the RA studies.
The study also raises the question of whether more physicians will now seek to use rituximab off-label in both forms of MS -- a practice that is already not uncommon. (At least half a dozen presentations are scheduled at the 2015 ECTRIMS meeting that describe clinical experience with rituximab in MS and related conditions such as neuromyelitis optica.)
Roche and Genentech are no strangers to having two competing drugs for a single condition, with one offered at a significantly cheaper price. The companies manufacture both bevacizumab (Avastin) and ranibizumab (Lucentis) for a host of ophthalmic conditions, and physicians have long preferred the cheaper bevacizumab, especially after studies largely showed equal efficacy and safety profiles between the two.
Whether such a situation will arise with rituximab-ocrelizumab remains speculative, but , at which point market pressures may force Roche/Genentech to drop the price for rituximab.
Several experts interviewed by ľֱ said the ocrelizumab data were the most exciting results presented at the meeting, and that although several other agents are available to treat relapsing-remitting disease, a newer agent with a better side effect profile is always welcome.
, co-director of the MS Center at the University of Colorado Denver, noted that ocrelizumab could be taken infrequently, would be well tolerated, with high efficacy and very good safety: "We will always be interested in a drug like that," he said.
The fact that ocrelizumab could be used to treat both forms of disease is appealing, said , director of the MS Center at Columbia University Medical Center.
"It's hard to tell in some patients" whether they're relapsing-remitting or primary progressive, Riley said. "What we need so desperately is a drug that will address both of those issues."
Disclosures
Hauser disclosed financial relationships with Hoffman La Roche, Symbiotix, and Bionure.
Primary Source
European Committee for Treatment and Research in Multiple Sclerosis
Hauser SL, et al "Efficacy and safety in relapsing multiple sclerosis -- results of the interferon-beta-1a-controlled, double-blind, phase III OPERA I and II studies" ECTRIMS 2015; Abstract 246.