Type of information: Granting of a Market Authorisation in the EU
Product name: Ocrevus™
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
- monoclonal antibody. Ocrelizumab is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells. CD20-positive B cells are a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage, which can result in disability in people with MS. Based on preclinical studies, ocrelizumab 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.
Company: Genentech, a member of Roche Group (USA - CA - Switzerland)
- primary progressive multiple sclerosis (PPMS)
- relapsing multiple sclerosis (RMS)
- • On January 8, 2018, the European Commission has granted marketing authorisation for Ocrevus® (ocrelizumab) for patients with active relapsing forms of multiple sclerosis defined by clinical or imaging features and for patients with early primary progressive multiple sclerosis in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity.
- • On November 10, 2017, the European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for Ocrevus® for the treatment of adult patients with relapsing multiple sclerosis (RMS) and early primary progressive multiple sclerosis (PPMS). Ocrevus® is the first medicine in the EU intended to treat some patients with PPMS. There are currently no disease-modifying therapies available for this particular form of MS. The recommendation from EMA’s CHMP is based on data from three pivotal Phase III clinical trials in 1,423 patients with MS (two in RMS and one in PPMS patients). Treatment with Ocrevus® significantly reduced the annualised relapse rate by 46.4% at 96 weeks compared with interferon beta-1a treatment in patients with RMS. For patients with PPMS, treatment with Ocrevus® led to a 24% reduction in the risk of 12-week confirmed disability progression compared with placebo. Data from the clinical trial in PPMS indicate that patients in the early stage of disease benefit more from the medicine. More investigation is needed to better understand how beneficial Ocrevus® might be in the more advanced stages of the disease. The most common adverse reactions observed with Ocrevus® are infusion-related reactions and infections. The CHMP therefore recommended that Ocrevus® treatment should be initiated and supervised by an experienced healthcare professional with access to appropriate medical support to manage severe reactions.
- • On July 17, 2017, Roche announced that Ocrevus™ (ocrelizumab) has been approved by the Australian Therapeutic Goods Administration (TGA) for the treatment of relapsing forms of multiple sclerosis and primary progressive multiple sclerosis, marking the second approval of Ocrevus™ for both indications following the FDA decision in the US in March 2017.
- • On March 28,2017, the FDA approved Ocrevus™ (ocrelizumab) to treat adult patients with relapsing forms of multiple sclerosis and primary progressive multiple sclerosis. This is the first drug approved by the FDA for primary progressive multiple sclerosis. The efficacy of Ocrevus™ for the treatment of relapsing forms of multiple sclerosis was shown in two clinical trials in 1,656 participants treated for 96 weeks. Both studies compared Ocrevus™ to Rebif® (interferon beta-1a). In both studies, the patients receiving Ocrevus™ had reduced relapse rates and reduced worsening of disability compared to Rebif®.
- In a study of PPMS in 732 participants treated for at least 120 weeks, those receiving Ocrevus™ showed a longer time to the worsening of disability compared to placebo. The FDA granted this application breakthrough therapy designation, fast track designation, and priority review.
• On December 20, 2016, Roche announced that the FDA has extended the Prescription Drug User Fee Act (PDUFA) date for its review of the Biologics Licence Application (BLA) of Ocrevus™ (ocrelizumab) to 28th March 2017. The extension is the result of the submission of additional data by Roche regarding the commercial manufacturing process of Ocrevus™, which required additional time for FDA review. The extension is not related to the efficacy or safety of Ocrevus™.
- • On June 26, 2016, Roche announced that the European Medicines Agency (EMA) has validated the company’s Marketing Authorisation Application (MAA) of Ocrevus® (ocrelizumab) for the treatment of relapsing multiple sclerosis and primary progressive multiple sclerosis in the European Union (EU). Validation confirms that the submission is complete and signifies the MAA is under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP).
- The FDA has also accepted for review Roche’s Biologics License Application (BLA) for Ocrevus® for the treatment of RMS and PPMS, and has granted the application Priority Review Designation with a targeted action date of 28 December 2016.
- The Ocrevus® marketing applications are based on positive results from three Phase III studies, which met primary and key secondary endpoints. Data from two identical studies (OPERA I and OPERA II) in people with RMS showed superior efficacy of Ocrevus in reducing annualised relapse rates and disability progression sustained for at least three and for at least six months compared with Rebif® (interferon beta-1a). Data from the ORATORIO study in people with PPMS showed significant reductions in disability progression sustained for at least three and for at least six months, as well as in other measures of progressive disease compared with placebo. Overall safety (proportion of patients with adverse events and serious adverse events) of Ocrevus in the Phase III studies was similar to interferon beta-1a in the RMS studies and to placebo in the PPMS study.
- Roche has also recently submitted regulatory applications in Switzerland and Australia.
- • On February 16, 2016, Genentech announced that the FDA has granted Breakthrough Therapy Designation for ocrelizumab (Ocrevus™) for the treatment of people with primary progressive multiple sclerosis. There are currently no approved treatments for this form of multiple sclerosis characterized by steadily worsening symptoms and typically without distinct relapses or periods of remission. Genentech plans to pursue marketing authorization for both primary progressive multiple sclerosis and relapsing multiple sclerosis. The company will submit data from three pivotal Phase III studies to the FDA in the first half of 2016.
- The Phase III clinical development program for ocrelizumab includes three studies: OPERA I, OPERA II and ORATORIO. ORATORIO is a Phase III, randomized, double-blind, global multi-center study evaluating the efficacy and safety of ocrelizumab (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 PPMS. OPERA I and OPERA II are Phase III, randomized, double-blind, double-dummy, global multi-center studies evaluating the efficacy and safety of ocrelizumab (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 (i.e., relapsing-remitting MS and secondary-progressive MS with relapses). In contrast to the OPERA I and OPERA II studies, where the blinded treatment period was two years, the blinded treatment period of the ORATORIO study continued beyond that until all patients had received at least 120 weeks of either ocrelizumab or placebo and a predefined number of CDP events was reached overall in the study.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-03-28
UE authorization: 2018-01-08
Favourable opinion UE: 2017-11-10
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: