Acapella: Real World Experience with Ocrelizumab: An Observational Study Evaluating Safety in Patients with Relapsing and Progressive MS

Background: Ocrelizumab (OCR) is a humanized, monoclonal antibody that targets CD20+ B cells and is FDA approved for treatment of relapsing remitting (RRMS) and primary progressive MS (PPMS). The pivotal Phase III clinical trials for RRMS (OPERA 1 and 2) included only subjects ages 18-55 with EDSS of 0-5.5 inclusive, and for the PPMS trial (ORATORIO), EDSS of 0-6.5 inclusive.

Objectives: We sought to compare the frequency of adverse events (AEs) in a real-world population receiving OCR with the clinical trial population, and to determine if AEs were more frequent in subjects with age and/or EDSS outside the inclusion/exclusion parameters of the Phase III trials.

Methods: The study includes all subjects receiving OCR at the Elliot Lewis Center in Wellesley, MA. Subjects will be followed for 5 years. Initial assessments include EDSS, brain MRI, mammograms (per local SOC guidelines), collection of medical history including prior serious or recurrent infections, history of malignancy and exposure to immunosuppressive treatment, JCV antibody with index and immunoglobulins, and a Patient Reported Outcomes (PROs) tool to aid in AE collection.

Results: Interim Data Analysis: As of October 27, 2017, 101 subjects enrolled: 28% are male, 72% female, age range 25–73, RRMS 56.4% and PMS (PPMS and transitioning RRMS) 43.6%. EDSS range was 0–7.5, with a median EDSS of 3.5; 12% had an EDSS of ≥6.5. 81% of patients had been on 1 or more DMTs prior to OCR treatment, including 17 transitioning from natalizumab (71% JCV +) to OCR, and 19% were treatment naïve.

27.7% of subjects experienced an infusion related reaction (IRR) during the first dose of OCR compared to approx. 28% in the ORCHESTRA data set (OPERA 1 and 2 and ORATORIO). The rate of infections for all OCR treated patients was 11% (1% bronchitis, 2% shingles, 5% URIs, 2% UTIs and 2% other infections (influenza and mastitis)). Subgroup analysis of IRR, infection, and AE incidence by subject age, EDSS and MS subtype is pending at the time of this abstract.

Conclusions: The ACAPELLA trial is a prospective observational study with a primary objective of assessing the occurrence of AEs in a real-world MS population. Interim data analyses will occur on a biyearly basis, and findings will be reported upon yearly. Interim Data Analysis 2 will occur in April 2018, with approximately 150 subjects estimated to be enrolled at that time. Thus far, the incidence of AEs is similar to that seen in OPERA and ORATORIO, but treatment duration has been less than one year in all subjects at time of this analysis. Additional topics of interest in the ACAPELLA population include outcomes of subjects with a prior history of malignancy/breast cancer or immunosuppressive treatment, the effect of continued OCR dosing on JCV index values and immunoglobulin levels over time, and changes in EDSS and MRI over the 5-year interval.