New analyses support Ocrelizumab ( Ocrevus ) significant benefit on disease progression in early-stage relapsing-remitting multiple sclerosis ( RRMS ) and primary progressive multiple sclerosis ( PPMS ) as well as demonstrating high persistence and strong adherence to twice-yearly ( six-monthly ) dosing.
Interim analysis phase IIIb ENSEMBLE
No evidence of disease progression in early-stage RRMS. Ocrelizumab treatment has provided consistent benefit over one year in patients who were recently diagnosed with RRMS and had not received prior disease modifying treatment ( DMT ) in an interim analysis of open-label study ENSEMBLE.
After 48 weeks, 85% of Ocrelizumab-treated patients have achieved no evidence of disease activity ( NEDA; no relapses, worsening of disability or new or enlarging brain lesions with pre-specified MRI re-baselining at 8 weeks ).
The average annualised relapse rate across all patients was very low ( 0.005 ) and their mean change in Expanded Disability Status Scale score ( EDSS ) from baseline significantly improved from 1.71 to 1.55 ( p=0.002 ).
Additionally, neurofilament light chain ( NfL ), a marker of nerve cell damage, was reduced to nearly healthy control levels with Ocrelizumab treatment ( 10.5 pg/mL at baseline to 4.55 pg/mL at 48 weeks with Ocrelizumab vs 4.12 pg/mL in healthy controls ).
The safety profile of Ocrelizumab in this trial was consistent with its overall favourable safety profile.
Post-hoc analysis phase III ORATORIO
Ocrelizumab treatment has significantly slowed accumulation of atrophied T2-lesion volume ( aT2-LV ) compared with placebo at 120 weeks in a post-hoc analysis of the ORATORIO study in PPMS ( 319 mm3 vs. 366 mm3 with placebo, p less than 0.015 ).
aT2-LV is a measure that reflects the volume of T2 lesions in brain tissue that is replaced by cerebrospinal fluid, and is believed to be a marker of disease progression in multiple sclerosis.
People with PPMS experience three to five times higher accumulation of aT2-LV than people with relapsing multiple sclerosis and these data have suggested that Ocrelizumab may favourably impact the underlying progressive biology of multiple sclerosis.
Ocrelizumab is the first and only therapy approved for both RMS ( including RRMS and active, or relapsing, SPMS ) and PPMS, with six-month dosing. Ocrelizumab is a humanized monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin and axonal damage. This nerve cell damage can lead to disability in people with multiple sclerosis.
Based on preclinical studies, Ocrelizumab binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, suggesting that important functions of the immune system may be preserved.
Ocrelizumab 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.
Multiple sclerosis is a chronic disease that affects up to a million people in the U.S. and more than 2.8 million people worldwide.
Multiple sclerosis occurs when the immune system abnormally attacks the insulation and support around nerve cells ( myelin sheath ) in the central nervous system ( 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.
Most people with multiple sclerosis experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.
People with all forms of multiple sclerosis experience disease progression ( permanent loss of nerve cells in the central nervous system and gradual worsening of disability ) at the beginning of their disease even if their clinical symptoms aren’t apparent or don’t appear to be getting worse.
Delays in diagnosis and treatment can negatively impact people with multiple sclerosis, both in terms of their physical, mental and financial health.
An important goal of treating multiple sclerosis is to slow the progression of disability as early as possible.
Relapsing-remitting multiple sclerosis ( 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. Approximately 85% of people with multiple sclerosis are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive multiple sclerosis ( SPMS ), in which they experience steadily worsening disability over time.
Relapsing forms of multiple sclerosis ( RMS ) include people with RRMS and people with SPMS who continue to experience relapses.
Primary progressive multiple sclerosis ( PPMS ) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15% of people with multiple sclerosis are diagnosed with the primary progressive form of the disease. ( Xagena )
Source: Roche, 2021