Roche’s Star MS Drug Snags EU Approval

OCREVUS is a humanised monoclonal antibody designed to 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 multiple sclerosis (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.

OCREVUS is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.

OPERA I and OPERA II are Phase III, randomised, double-blind, double-dummy, global multi-centre studies evaluating the efficacy and safety of OCREVUS (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. In these studies, relapsing MS (RMS) was defined as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. A similar proportion of patients in the OCREVUS group experienced serious adverse events and serious infections compared with patients in the high-dose interferon beta-1a group in the RMS studies.

ORATORIO is a Phase III, randomised, double-blind, global multi-centre study evaluating the efficacy and safety of OCREVUS (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 primary progressive MS (PPMS). The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either OCREVUS or placebo and a predefined number of confirmed disability progression (CDP) events was reached overall in the study. A similar proportion of patients in the OCREVUS group experienced adverse events and serious adverse events compared with patients in the placebo group in the PPMS study.

A summary of the data from the OPERA I, OPERA II and ORATORIO studies that support this approval is below.

Key data in RMS patients treated with OCREVUS showed:

• A 46 percent and 47 percent relative reduction in the annualised relapse rate (ARR) compared with interferon beta-1a over the two-year period in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
• A 40 percent relative risk reduction in confirmed disability progression (CDP) sustained for 12 weeks compared with interferon beta-1a in a pooled analysis of OPERA I and OPERA II, as measured by the Expanded Disability Status Scale (EDSS) (p=0.0006).
• A 94 percent and 95 percent relative reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
• A 77 percent and 83 percent relative reduction in the total number of new and/or enlarging T2 lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
• A 64 percent and 89 percent relative increase in the proportion of patients with No Evidence of Disease Activity (NEDA) compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).

Key data in PPMS patients treated with OCREVUS showed:

• A 24 percent relative risk reduction in CDP sustained for at least 12 weeks compared with placebo, as measured by the EDSS (p=0.0321).
• A 25 percent relative risk reduction in CDP sustained for at least 24 weeks compared with placebo, as measured by the EDSS (p=0.0365).
• A 29.4 percent relative reduction in progression rate of walking impairment compared with placebo over 120 weeks measured by the timed 25-foot walk (p=0.0404).
• A 3.4 percent reduction in volume of brain hyperintense T2 lesions compared with a 7.4 percent increase in volume in placebo-treated patients over 120 weeks (p<0.0001).

The most common side effects associated with OCREVUS in all Phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.

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.^4,5 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.^6,7,8 Most people with MS experience their first symptom between 20 and 40 years of age, making the disease a leading cause of non-traumatic disability in younger adults.⁵

Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterised by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery.^9,10 Approximately 85 percent of people with MS are initially diagnosed with RRMS.³ The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time.³ Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses.

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.¹¹ Approximately 15 percent of people with MS are diagnosed with the primary progressive form of the disease.³ Disability accumulates twice as fast in PPMS as in RMS, meaning that people with PPMS may have to rely on mobility aids or become wheelchair bound, are unable to work, and need carers to look after them sooner.¹² Additionally, a recent article in Multiple Sclerosis Journal noted that the quality of life for a person with MS with severe disability (Expanded Disability Status Scale >7), as measured by EQ-5D mean utility scores, ranks among the worst for chronic conditions.¹³ There is a profound burden on people living with PPMS and a clear clinical need to initiate treatment as early as possible to control disease activity and disability progression.

People with all forms of MS experience disease activity – inflammation in the nervous system and permanent loss of nerve cells in the brain – even when their clinical symptoms aren’t apparent or don’t appear to be getting worse.¹⁴ An important goal of treating MS is to reduce disease activity as soon as possible to slow how quickly a person’s disability progresses.¹⁵ Despite available disease-modifying treatments (DMTs), some people with RMS continue to experience disease activity and disability progression.