New Data Proves Efficacy of Relapsing Multiple Sclerosis Treatment

This morning, Genentench released data regarding its drug, ocrelizumab (OCREVUS), at the 70^th American Academy of Neurology (AAN) Annual Meeting, which indicate efficacy in relapsing multiple sclerosis (RMS).

Ocrelizumab is a humanized monoclonal antibody engineered to target CD20-positive B cells, which are specific types of immune cells believed to be key contributors to and axonal (nerve cell) damage and myelin (nerve cell insulation and support). It is intended to be administered every 6 months by intravenous infusion. The initial doses are given 2 weeks apart as a pair of 300 mg infusions. Following doses are given as single 600 mg infusions.¹

Ocrelizumab has been developed to bind to the CD20 cell surface proteins expressed on certain B cells but not on stem cells or plasma cells. Preclinical studies have shown that, with this, important functions of the immune system may be preserved.

Relapsing multiple sclerosis (RMS) is an indication that includes both people with relapsing-remitting multiple sclerosis (RRMS) and people with secondary progressive multiple sclerosis (SPMS) who continue to experience relapses in which new or worsening signs of multiple sclerosis symptoms develop.

Several measures in the newly presented data display the underlying disease activity and disability progression, such as magnetic resonance imaging (MRI), cognitive function, and spinal fluid biomarkers of inflammation and neurodegeneration. The drug’s safety also maintained a consistent favorable benefit-risk profile. As shown in a platform presentation, by measuring brain MRI activity through the randomized and open-label extension (OLE) periods of the Phase III studies, patients with RMS experienced a sustained reduction in underlying disease activity after 4 years of continuous treatment with ocrelizumab.⁴

In addition, patients who stayed on ocrelizumab maintained low numbers of T1 gadolinium-enhancing (T1Gd+) lesions (0.017 pre-OLE to 0.17 T1Gd+ lesions per scan at year 4 [year 2 of the OLE phase]) and new/enlarging T2 (N/ET2) lesions [0.052 pre-OLE to 0.080 N/ET2 lesions per scan] through year 2 of the OLE phase.

In the presentation at AAN, a second 4-year analysis indicated that those who stayed on ocrelizumab through year 2 of the OLE period sustained low annualized relapse rates (ARR) and 24-week confirmed disability progression (CDP24). Additionally, patients who switched from interferon beta-1a to ocrelizumab experienced a significant decline in ARR by year one that was maintained through year 2.³

New cognitive performance data that was also shared in a platform presentation showed people with RMS who were administered ocrelizumab reduced the risk of 12- and 24-week confirmed cognitive decline (as defined by confirmed worsening on the Symbol Digit Modalities Test [SDMT] of at least four points) by 38% and 39% (p≤0.001 and p=0.002, respectively) during the 96-week period.

Additionally, pooled OPERA I and OPERA II (Phase III studies in relapsing forms of multiple sclerosis) data from a separate presentation indicate scores of at least 4 and 2 points, (as determined by baseline Expanded Disability Status Scale [EDSS] and pyramidal Kurtzke Functional Systems scores), respectively, and treated with ocrelizumab experienced a significant improvement in cognitive function through 96 weeks in those with RMS at increased risk of progressive disease (as determined by baseline Expanded Disability Status Scale [EDSS] and pyramidal Kurtzke Functional Systems.²

In another platform presentation, ocrelizumab was shown to reduce the presence of nerve damage and inflammation biomarkers in spinal fluid (cerebrospinal fluid or CSF), including median concentration of neurofilament light chain (Nf-L) (week 12: −24%, week 24: −47%) and median number of CD19+ B cells (week 12: −86%, week 24: −82%), respectively, in 12 to 24 weeks.⁵

In over 55 countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia, Switzerland, and the European Union, ocrelizumab is now approved

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References:

1. New OCREVUS (Ocrelizumab) Data at AAN Demonstrate Significant Reductions in Disease Activity and Disability Progression in Relapsing Multiple Sclerosis. https://www.businesswire.com/news/home/20180422005102/en/New-OCREVUS-Ocrelizumab-Data-AAN-Demonstrate-Significant. Accessed April 23, 2018.
2. Impact of Ocrelizumab on Cognition in Patients at Increased Risk of Progressive Disease. https://submissions.mirasmart.com/Verify/AAN2018/submission/temp/radC35B6.pdf. Accessed April 23. 2018.
3. Annualized Relapse Rate and Confirmed Disability Progression in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the Open-Label Extension Period of the Phase III Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis. https://submissions.mirasmart.com/Verify/AAN2018/submission/temp/rad64A5A.pdf. Accessed April 23, 2018.
4. Brain MRI Activity and Atrophy Measures in Patients Receiving Continuous Ocrelizumab or Switching From Interferon Beta-1a to Ocrelizumab Therapy in the OpenLabel Extension Period of the Phase III Trials of Ocrelizumab in Patients With Relapsing Multiple Sclerosis. https://submissions.mirasmart.com/Verify/AAN2018/submission/temp/radB37Cpdf. Accessed April 23, 2018.
5. Interim Analysis of the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Study in Multiple Sclerosis (MS). https://submissions.mirasmart.com/Verify/AAN2018/submission/temp/rad2E1DA.pdf. Accessed April 23, 2018.