October 9, 2015
Roche’s ocrelizumab first investigational medicine to show positive pivotal study results in both relapsing and primary progressive forms of multiple sclerosis
- Ocrelizumab showed superiority to interferon beta-1a (Rebif®) in two identical Phase III studies in people with relapsing multiple sclerosis (MS), the most common form of the disease
- Ocrelizumab is the first investigational medicine to show efficacy in people with primary progressive MS in a large Phase III study
- Ocrelizumab Phase III data will be presented at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) from 7th to 10th October in Barcelona, Spain
(The following text is extracted from the Roche press release which contains much more specific data
Check out this link for the MS Society report on ocrelizumab )
Roche today announced data from three positive, pivotal Phase III studies of ocrelizumab in people with relapsing multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS). Data from two identical studies (called OPERA I and OPERA II) in people with relapsing MS, which affects approximately 85 percent of people with MS at the time of diagnosis, showed ocrelizumab was superior to interferon beta-1a (Rebif®), a well-established MS therapy, in reducing the three major markers of disease activity over the two-year controlled treatment period.
In a separate study (called ORATORIO) in people with PPMS, a form of the disease marked by steadily worsening symptoms and typically without distinct relapses or periods of remission, ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks (the primary endpoint) and 24 weeks (a secondary endpoint) compared with placebo. Additionally, the study met other secondary endpoints of reducing the time required to walk 25 feet, the volume of chronic inflammatory brain lesions, and brain volume loss.
“…………….. “The findings may also encourage the MS community to look more closely at earlier treatment of the disease. Currently, many doctors reserve what are considered highly effective MS medicines until a patient’s disease becomes more advanced. Patients and their doctors need new treatment options that offer the potential for greater efficacy than a standard-of-care interferon with a similar safety profile.”
“This is an important moment for the MS community,” said 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. “For decades, trial after trial has failed to show the benefit of any medicine for people with primary progressive MS. Now, for the first time, we have a positive Phase III study result for people with this debilitating form of the disease.”
Roche plans to pursue marketing authorisation for ocrelizumab in relapsing MS and in PPMS. Data from the ocrelizumab OPERA I and OPERA II studies and from the ORATORIO study will be submitted to global regulatory authorities in early 2016.
About the OPERA I and OPERA II studies in relapsing MS
Results from the OPERA I and OPERA II studies will be presented by Dr. Hauser on Friday, 9th October (Abstract #246, 14:40 – 14:52 CET). OPERA I and OPERA II are Phase III, randomised, double-blind, double-dummy, global multi-centre 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).1
In the OPERA I and OPERA II studies, ocrelizumab significantly reduced the annualised relapse rate (ARR) by nearly 50 percent compared with interferon beta-1a over the two-year period. Additionally, ocrelizumab met secondary endpoints of the study, significantly delaying confirmed disability progression by approximately 40 percent sustained for both 12 and 24 weeks compared with interferon beta-1a, Ocrelizumab also significantly reduced acute MS-related inflammation and brain injury at 24, 48 and 96 weeks by more than 90 percent and the emergence of more chronic or growing areas of MS-related brain injury at 24, 48 and 96 weeks by around 80 percent compared with interferon beta-1a.
Data from the Phase III studies in patients with relapsing MS showed:
- A 46-percent and 47-percent reduction in the ARR compared with interferon beta-1a over the two-year period in OPERA I and OPERA II.
- A 43-percent and 37-percent risk reduction in CDP sustained for 12 weeks compared with interferon beta-1a in OPERA I and OPERA II.
- A 43-percent and 37-percent risk reduction in CDP sustained for 24 weeks compared with interferon beta-1a in OPERA I and OPERA II.
- A 94-percent and 95-percent reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a in OPERA I and OPERA II.
- A 77-percent and 83-percent reduction in the total number of new and/or enlarging hyperintense T2 lesions compared with interferon beta-1a in OPERA I and OPERA II
The ORATORIO study met its primary endpoint, showing treatment with ocrelizumab significantly reduced the risk of progression of clinical disability sustained for at least 12 weeks by 24 percent compared with placebo, Additionally, ocrelizumab was superior to placebo in significantly reducing the risk of progression of clinical disability for at least 24 weeks by 25 percent and the time required to walk 25 feet over 120 weeks by 29 percent and alsodecreased the volume of hyperintense T2 lesions by 3.4 percent over 120 weeks,
Overall, the proportion of patients in the ocrelizumab group with adverse events was similar to placebo (95.1 percent vs. 90.0 percent, respectively); the most common adverse event associated with ocrelizumab was infusion-related reactions (39.9 percent vs. 25.5 percent for placebo). The proportion of patients in the ocrelizumab group with serious adverse events, including serious infections, was also similar to placebo (20.4 percent vs. 22.2 percent, respectively).