Roche's ocrelizumab first investigational medicine to show efficacy in people with primary progressive multiple sclerosis in large Phase III study
Basel, 28 September 2015
Phase III study meets primary endpoint in debilitating form of multiple sclerosis with no approved treatments
Ocrelizumab is the first investigational medicine to show positive study results in both primary progressive and relapsing forms of multiple sclerosis
Roche will submit data to global regulatory authorities for both forms of multiple sclerosis in early 2016
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced positive results from a pivotal Phase III study that evaluated the investigational medicine ocrelizumab in people 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.
"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, M.D., Roche's 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 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 B 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, M.D., Ph.D., Chair of the Scientific Steering Committee of the ORATORIO study and Professor of Neurology and Neuroimmunology at Vall d'Hebron University Hospital and Research Institute, Barcelona, Spain, on Saturday, 10th October (Abstract #228, 8:52 - 9:03 CET) in Barcelona, Spain.
Additionally, Phase III results in people with relapsing MS (OPERA I and OPERA II studies) will be presented at ECTRIMS by Stephen Hauser, M.D., Chair of the Scientific Steering Committee of the OPERA studies and Chair of the Department of Neurology at the University of California San Francisco School of Medicine, on Friday, 9th October (Abstract #190, 14:40 - 14:52 CET).
Roche 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 global regulatory authorities in early 2016.
About the ORATORIO study
ORATORIO is a Phase III, randomised, double-blind, global multi-centre 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.1 The primary endpoint of the ORATORIO study was time to onset of confirmed disability progression (CDP), defined as an increase in EDSS that is sustained for at least 12 weeks.
Ocrelizumab is an investigational, humanised 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.
In addition to ORATORIO, the Phase III clinical development programme for ocrelizumab includes OPERA I and OPERA II, which are randomised, double-blind, double-dummy, global multi-centre studies in people with relapsing forms of MS.2,2
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 the nerve cells (myelin sheath) in the brain, spinal cord and optic nerves, causing inflammation and consequent damage.5,6 Damage to these nerve cells can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability.5 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.7,8
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 (periods of time when symptoms flare) 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.
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche's personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. 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 chemotherapy.
In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. 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 roche.com.
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1. F. Hoffmann-La Roche. ClinicalTrials.gov NCT01194570. National Library of Medicine. Available at: https://clinicaltrials.gov/ct2/show/NCT01194570.
2. 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.
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. Constant SL. (1999). B lymphocytes as antigen-presenting cells for CD4+ T cell priming in vivo. J Immunol, 162(10):5695-5703.
6. Crawford A, et al. (2006). Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol, 176(6):3498-3506.
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8. MS International Federation. What is MS? Available at http://www.msif.org/about-ms/what-is-ms/.
9. MS International Federation. Types of MS. Available at: http://www.msif.org/about-ms/types-of-ms/.