Roche's marketing applications for review of OCREVUS® (ocrelizumab) in two forms of multiple sclerosis accepted by EMA and FDA

• OCREVUS is the first investigational medicine seeking marketing authorisation for both relapsing and primary progressive multiple sclerosis (MS)
• FDA grants Priority Review Designation for OCREVUS Biologics License Application (BLA)

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today 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 (RMS) and primary progressive multiple sclerosis (PPMS) 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 U.S. Food and Drug Administration (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. If approved by the EMA and FDA for both indications, OCREVUS would be the first and only treatment for both forms of multiple sclerosis (MS), which affect approximately 95 percent of people at diagnosis.

“OCREVUS is the first investigational medicine to significantly reduce disability progression in people with relapsing and primary progressive forms of MS,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are pleased by the acceptance of our marketing applications for OCREVUS, which we believe has the potential to help people living with either of these two forms of MS. We will continue to work closely with the EMA and FDA to bring this investigational medicine to people with MS as quickly as possible.”

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. The most common adverse events associated with OCREVUS were infusion-related reactions and infections, which were mostly mild to moderate in severity.

Priority Review Designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment of a serious disease. In February 2016, the FDA granted Breakthrough Therapy Designation to OCREVUS for the treatment of PPMS. OCREVUS is the first investigational medicine to receive Breakthrough Therapy Designation in MS.

If the EMA’s CHMP adopts a positive opinion that is endorsed by the European Commission, OCREVUS will be granted a marketing authorization that will be valid in all 28 member states of the EU.

Roche has also recently submitted regulatory applications in Switzerland and Australia.

OCREVUS® is the proprietary name submitted to global regulatory authorities for the investigational medicine ocrelizumab.

About OCREVUS® (ocrelizumab)

OCREVUS is an investigational, humanised monoclonal antibody designed to selectively 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 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.

The Phase III clinical development programme for OCREVUS (ORCHESTRA) includes three studies: OPERA I, OPERA II and ORATORIO. OPERA I and OPERA II are identical Phase III, randomised, double-blind, double-dummy, global multi-centre studies that evaluated the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with Rebif® (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).¹ORATORIO is a Phase III, randomised, double-blind, global multi-centre study that evaluated the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with placebo in 732 people with primary progressive MS (PPMS).²

About multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects an estimated 2.3 million people around the world, for which there is currently no cure.^3,4 MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the brain, spinal cord and optic nerves, causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability.^5,6,7 Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.⁸

Relapsing MS is the most common form of the disease. Disease activity and progression can occur even when people do not show signs or symptoms of MS, despite available relapsing MS treatments. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission.⁹ Approximately one in 10 people with MS are diagnosed with the primary progressive form of the disease. There are no approved treatments for PPMS.

About Roche in neuroscience

Neuroscience is a major focus of research and development at Roche. The company’s goal is to develop treatment options based on the biology of the nervous system to help improve the lives of people with chronic and potentially devastating diseases. Roche has more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, Alzheimer’s disease, spinal muscular atrophy, Parkinson’s disease, Down syndrome and autism.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry seven years in a row by the Dow Jones Sustainability Indices.

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2015 employed more than 91,700 people worldwide. In 2015, Roche invested CHF 9.3 billion in R&D and posted sales of CHF 48.1 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law. Rebif is a registered trademark of Merck KGaA and EMD Serono, Inc.

References

1. F. Hoffmann-La Roche. ClinicalTrials.gov NCT01247324 and NCT01412333. National Library of Medicine. Available at: https://clinicaltrials.gov/ct2/show/NCT01247324 and https://clinicaltrials.gov/ct2/show/NCT01412333.
2. F. Hoffmann-La Roche. ClinicalTrials.gov NCT01194570. National Library of Medicine. Available at: https://clinicaltrials.gov/ct2/show/NCT01194570.
3. Multiple Sclerosis International Federation. (2013). Atlas of MS 2013. Available at: http://www.msif.org/about-us/advocacy/atlas/.
4. National Institutes of Health-National Institute of Neurological Disorders and Stroke. (2015). Multiple Sclerosis: Hope Through Research. Available at: http://www.ninds.nih.gov/disorders/multiple_sclerosis/detail_multiple_sclerosis.htm#280373215.
5. Ziemssen T. (2005). Modulating processes within the central nervous system is central to therapeutic control of multiple sclerosis. J Neurol, 252(Suppl 5), v38-v45.
6. Hauser S.L. et al. (2012). Multiple sclerosis and other demyelinating diseases. In Harrison’s Principles of Internal Medicine (pp.3395-3409). New York, NY: McGraw Hill Medical.
7. Hadjimichael O. et al. (2007). Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain, 127(1-2), 35-41.
8. Multiple Sclerosis International Federation. What is MS? Available at http://www.msif.org/about-ms/what-is-ms/. Last accessed January 2015.
9. MS International Federation. Types of MS. Available at: http://www.msif.org/about-ms/types-of-ms/.