Roche drug shows promise against hard-to-treat MS

Patients with the hard-to-treat 'primary progressive' form of multiple sclerosis could benefit from a new drug.

Roche's biotech division Genentech has just released a preview of phase III data from its ORATORIO study, which shows ocrelizumab reduced progression of the condition for at least 12 weeks.

The firm says the monoclonal antibody is the first ever drug to show efficacy against primary progressive multiple sclerosis (PPMS), which affects around 10 per cent of patients, and currently has no approved treatments.

Ocrelizumab has already shown efficacy against the more common relapsing forms of the disease, and outperformed Merck Serono's Rebif (interferon beta-1a) in its head-to-head OPERA phase III trials earlier this year.

The new data adds to existing predictions of the drug becoming a major player in the therapy area, rivalling new treatments such as Biogen's oral drug Tecfidra.

Ocrelizumab is given as an intravenous infusion every six months, in the form of two infusions two weeks apart.

Genentech says it is preparing to file with the US FDA in early 2016, and analysts predict ocrelizumab could earn around $800 million by 2020 if approved.

The ORATORIO study met its primary endpoint, showing ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo, as measured by the Expanded Disability Status Scale (EDSS).

"People with the primary progressive form of MS typically experience symptoms that continuously worsen after the onset of their disease, and there are no approved treatments for this debilitating condition," said Sandra Horning, MD, chief medical officer and head of Global Product Development. "Ocrelizumab is the first investigational medicine to show a clinically meaningful and statistically significant effect on the progression of disease in primary progressive MS."

The level of adverse events (AE) was also reassuring, being similar to placebo, with mild-to-moderate infusion-related reactions. Serious AE numbers, such as infections, were also similar to placebo – good news as the drug had originally been developed for rheumatoid arthritis (RA) and lupus nephritis, but was abandoned because of serious infections.

Ocrelizumab works by targeting the CD20 antibody, a mechanism Genentech researchers know well from Rituxan/Mabthera (rituximab), for non-Hodgkin's Lymphomas and RA which it co-developed with Idec and launched in 1997.

Genentech says its latest results validate the longstanding hypothesis that B cells are central to the underlying biology of MS. But it is not the only company with a CD20 antibody in the running: Novartis recently acquired all rights to Arzerra (ofatumumab) from GSK for $1billion to develop it as a treatment for MS.

Top-line data from the OPERA and ORATORIO studies will be presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) conference in Barcelona, on 9 and 10 October, respectively.