Phase III positive results from ORATORIO trial of ocrelizumab in primary progressive multiple sclerosis- Genentech + Roche

Genentech has announced positive results from a pivotal Phase III study that evaluated the investigational medicine ocrelizumab in patients with primary progressive multiple sclerosis (PPMS). The study (called ORATORIO) met its primary endpoint, showing treatment with 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). Overall, the incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was also similar to placebo.

The positive study results observed with ocrelizumab in both people with PPMS (ORATORIO) as well as those with relapsing forms of MS (OPERA I and OPERA II) validate the hypothesis that beta cells are central to the underlying biology of the disease. Top-line data from the ORATORIO study will be presented as a late-breaking abstract at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) by Xavier Montalban, chair of the Scientific Steering Committee of the ORATORIO study, on 10 October.

Additionally, Phase III results in patients with relapsing MS (OPERA I and OPERA II studies) will be presented at ECTRIMS by Stephen Hauser, chair of the Scientific Steering Committee of the OPERA studies, on 9 October.

Genentech plans to pursue marketing authorisation 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 the FDA in early 2016.

Comment: Ocrelizumab may be defined by its results in primary progressive MS, where it could become the first drug to gain approval for this difficult-to-treat population that comprises nearly 10% of patients. Novartis' oral sphingosine 1-phosphate receptor (S1PR) modulator Gilenya (fingolimod) failed at Phase III in PPMS leaving ocrelizumab the leading product in this indication.