Roche to present positive results from Ocrevus phase III trial programme in people with RMS and PPMS at EAN congress

Ocrevus significantly reduced disease activity and disability progression in patients with RMS and PPMS, as measured by No Evidence of Progression or Active Disease (NEPAD), a novel composite endpoint in MS. In RMS, Ocrevus significantly increased the proportion of patients maintaining NEPAD by 82 percent compared with Rebif (interferon beta-1a) at 96 weeks in a pooled exploratory analysis of the phase III OPERA I and II studies (p<0.001). In PPMS patients, Ocrevus more than tripled the proportion of those who maintained NEPAD compared with placebo at 120 weeks in an exploratory analysis of the phase III ORATORIO study (29.9 per cent with Ocrevus versus 9.4 per cent with placebo, p<0.001).

NEPAD is considered a clinically meaningful endpoint because it signifies a patient has no relapses, no confirmed disability progression measured by the Expanded Disability Status Scale (EDSS), no progression equal to or above 20 percent on the timed 25-foot walk (T25-FW) and the nine-hole peg test (9-HPT), no gadolinium-enhancing T1 MRI lesions and no new or enlarging T2 MRI lesions.

“These results underline that the significant effects of Ocrevus on disability progression are clinically meaningful,” said Ludwig Kappos, MD, Chair of the Department of Neurology, University Hospital, Basel, Switzerland. “Slowing disability progression, or preventing people with MS from having to use a cane or wheelchair, makes a great difference to their daily lives. It is particularly exciting to see these benefits in people with PPMS, a disabling form of MS without approved treatments in Europe.”

In separate post-hoc analyses of the OPERA I and II studies, Ocrevus significantly reduced the risk of patients with RMS losing the ability to walk long distances unassisted (EDSS =4) or requiring a cane or crutch (EDSS =6) compared with interferon beta-1a at 96 weeks (p=0.005). In the ORATORIO study, Ocrevus significantly reduced the risk of becoming wheelchair-bound (EDSS =7) compared with placebo at 120 weeks in PPMS patients with baseline EDSS =6 (p=0.028).

Furthermore, in a post-hoc analysis of the placebo-controlled ORATORIO study, Ocrevus consistently reduced the risk of 12- and 24-week confirmed disability progression (CDP) across three different definitions of the measure meant to capture more severe disability worsening than traditionally assessed in PPMS patients.

In addition, interim results from FLOODLIGHT, a sensor-based digital monitoring study to determine adherence and correlation with in-clinic testing in people with and without MS, will be presented. Pregnancy outcomes in all female patients treated with Ocrevus will also be presented.

The most common side effects associated with Ocrevus in all Phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.

Ocrevus is approved for use in the US. The Ocrevus Marketing Authorisation Application (MAA) has been validated by the European Medicines Agency (EMA) and is currently under review.

OPERA I and OPERA II are phase III, randomised, double-blind, double-dummy, global multi-centre studies evaluating the efficacy and safety of Ocrevus (600 mg administered by intravenous infusion every six months) compared with interferon beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 people with relapsing forms of MS. In these studies, relapsing MS (RMS) was defined as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. A similar proportion of patients in the Ocrevus group experienced serious adverse events and serious infections compared with patients in the high-dose interferon beta-1a group in the RMS studies.

ORATORIO is a phase III, randomised, double-blind, global multi-centre study evaluating the efficacy and safety of Ocrevus (600 mg administered by intravenous infusion every six months; given as two 300 mg infusions two weeks apart) compared with placebo in 732 people with primary progressive MS (PPMS). The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either Ocrevus or placebo and a predefined number of confirmed disability progression (CDP) events was reached overall in the study. A similar proportion of patients in the Ocrevus group experienced adverse events and serious adverse events compared with patients in the placebo group in the PPMS study.

Ocrevus is a humanised monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with multiple sclerosis (MS). Based on preclinical studies, Ocrevus binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.

Ocrevus is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.

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