Treatment with Ocrevus (ocrelizumab) slows disability progression in primary progressive multiple sclerosis (PPMS) in ways that may be of considerable importance to patients — including the possibility of delaying the need for a wheelchair by up to seven years, according to new data from a Phase 3 study.
Genentech, which developed and markets Ocrevus, will detail this and other latest clinical data in a series of oral and poster presentations at the 4th Congress of the European Academy of Neurology (EAN), running in Lisbon from June 16 to 19.
New analysis of data collected during the extended period of the Phase 3 ORATORIO study (NCT01194570) continue to demonstrate its benefits in PPMS patients, the presentations show.
Of note, researchers found that Ocrevus-treated patients, compared to a placebo group, had a 46% lesser risk of progressing to a wheelchair, based on data using 24-week confirmed disability progression (as measured by the length of time until a person reaches Expanded Disability Status Scale seven or greater, or EDSS≥7).
Data extrapolation suggested that treatment with Ocrevus could delay the need for a wheelchair by seven years compared to placebo, with the median time-to-wheelchair estimated to be 19.2 years for Ocrevus-treated PPMS patients and 12.1 years for the placebo group.
In general, the disability progression rate for placebo patients in the ORATORIO trial was of 12.1 years (median time of reaching EDSS≥7 and possibly being reliant on a wheelchair). The rate is similar to the median 12.4 years reported in untreated PPMS patients in the real-world MSBase registry.
“To a person living with primary progressive MS, for whom disability accumulates twice as fast as in relapsing MS, seven more years without the need for a wheelchair could extend the time they can live independently in their home, continue working or looking after their families,” Helmut Butzkueven, professor and chair of MS and Neuroimmunology Research at Central Clinical School, Monash University, said in a press release.
Safety data, covering 3,778 relapsing MS and PPMS patients and representing 9,474 patient years of exposure to Ocrevus, were also consistent with finding in Phase 3 clinical trials, the study noted.
These results will be discussed at the EAN meeting and are in the study “Risk of Becoming Wheelchair-Confined in Patients With Primary Progressive Multiple Sclerosis: Data From the ORATORIO Trial and a Long-Term Real-World Cohort From MSBase Registry.”
New trials opening
Two new Phase 3b clinical trials, ORATORIO-HAND and CONSONANCE (NCT03523858), are also planned to further evaluate MS progression and Ocrevus’ benefit in maintaining upper-limb strength, Genentech announced in the release.
ORATORIO-HAND will be the first study to evaluate the long-term safety and efficacy of Ocrevus in people with late-stage PPMS, and an EDSS disability score of 3-8. The randomized, placebo-controlled trial is expected to open in late 2018, and to enroll about 1,000 PPMS patients.
It will focus on measurements of preserved arm, wrist and hand function in treated patients, as well as delays in disability progression.
“Addressing the needs of people with progressive MS, who are typically more advanced in their disease course, is one of the major frontiers in MS research. Around a third of people living with progressive MS may already be confined to a wheelchair, so maintaining hand and arm function is essential for them to stay independent and lead active lives,” said the trial’s lead investigator, Gavin Giovannoni, a professor of neurology at Barts and The London School of Medicine and Dentistry, Queen Mary University .
“We’re pleased that in collaboration with Roche and Genentech, we will conduct a clinical trial that uses hand function as a primary outcome for the first time,” Giovannoni added.
The four-year, open-label Phase 3b CONSONANCE trial will assess the Ocrevus’ efficacy in both PPMS and secondary progressive MS (SPMS). It primary goals are determining the long-term impact of treatment using new composite disability endpoints — No Evidence of Progression (NEP) and No Evidence of Progression sustained for 24 or more weeks and Active Disease (NEPAD), in addition to other standard measurements.
Currently recruiting at 84 sites across the U.S., Canada, Europe and elsewhere, the trial is expected to enroll about 600 progressive MS patients.
CONSONANCE will also assess if using Roche and Genentech’s proprietary FLOODLIGHT mobile monitoring technology can help detect disability progression earlier than conventional clinical measures.
FLOODLIGHT study and PPMS forum
Results from a previous pilot study (NCT02952911), recently presented at AAN 2018, showed that the FLOODLIGHT mobile technology can work as a complement to in-clinic testing to provide a more complete and consistent picture of a patient’s disease activity, course, and progression.
Genentech is also launching the FLOODLIGHT Open global study, which is expected to enroll 10,000 MS patients worldwide. An open access database with the collected information will be created and made accessible to the MS research community.
More information on the FLOODLIGHT Open study is available here.
Finally, Genentech will host a live forum in parallel to the EAN 2018 meeting. Taking place June 18, from 4 to 5 p.m. CEST, the forum “Maintaining Independence in Progressive Multiple Sclerosis” will look at the impact of MS disability progression, with a focus on the importance and inherent value of living independently.
Registration for live streaming of the forum can be found here.