Ocrelizumab Positive in Primary Progressive MS

Pauline Anderson

September 29, 2015

The investigational drug ocrelizumab significantly reduces progression of clinical disability compared with placebo in patients with primary progressive multiple sclerosis (PPMS), topline results of a pivotal phase 3 study (ORATORIO) released by Roche show.

"Ocrelizumab is the first investigational medicine to show a clinically meaningful and statistically significant effect on the progression of disease in primary progressive MS," Sandra Horning, MD, Roche's chief medical officer and head of global product development, said in a press release.

The injectable humanized monoclonal antibody is also showing promise in relapsing forms of MS. Ocrelizumab is designed to selectively target CD20-positive B cells, immune cells thought to be a key contributor to myelin and axonal damage in MS.

B Cells Central

The new positive results validate the hypothesis that B cells are central to the underlying biology of the disease, according to the press release.

According to preclinical studies, ocrelizumab does not bind to stem cells or plasma cells. This suggests that important functions of the immune system may be preserved.

ORATORIO is a randomized, double-blind, multicenter study evaluating the efficacy and safety of ocrelizumab (600 mg administered by intravenous infusion every 6 months; given as two 300-mg infusions 2 weeks apart) compared with placebo in 732 patients with PPMS. Its primary endpoint, which was met, was time to onset of confirmed disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) that is sustained for at least 12 weeks.

Overall, the incidence of adverse events (AEs) associated with ocrelizumab was similar to that seen with placebo. The most common AEs were mild-to-moderate infusion-related reactions. The incidence of serious AEs, including serious infections, was also similar between the treatment and placebo groups.

There are currently no approved treatments for PPMS.

In addition to ORATORIO, Roche's phase 3 clinical development program for ocrelizumab includes two randomized, double-blind, double-dummy, multicenter studies in people with relapsing forms of MS (OPERA I and OPERA II).

These studies, too, are reporting positive topline results. Results released in July showed that compared with the interferon β-1a Rebif (EMD Serono/Pfizer), treatment with ocrelizumab significantly reduced the annualized relapse rate as well as the progression of clinical disability as measured by the EDSS, and the number of lesions in the brain on MRI.

Researchers will present topline data from the ORATORIO study at the upcoming European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in Barcelona, Spain. They will also release full phase 3 results of OPERA I and OPERA II.

Roche plans to pursue marketing authorization for ocrelizumab in relapsing MS and in PPMS. Data from the OPERA I and II studies and from the ORATORIO study will be submitted to global regulatory authorities in early 2016.

The current market for MS drugs is worth an estimated $20 billion a year. It mostly includes drugs for relapsing MS. Treatments already on the market include long-standing interferons, several oral agents, and injectables such as natalizumab (Tysabri, Biogen) and alemtuzumab (Lemtrada, Sanofi).

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