#ACTRIMS2019 — Use of Ocrevus at Cleveland Clinic Backs Phase 3 Trial Data
The data was presented in a poster session Feb. 28, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. The poster was titled “Real-World Experience with Ocrelizumab.”
Ocrevus, marketed by Genentech, was the first therapy approved by the U.S. Food and Drug Administration (FDA) to treat both relapsing multiple sclerosis and primary progressive multiple sclerosis (PPMS).
The effectiveness and safety of Ocrevus in relapsing MS and PPMS patients were demonstrated in three Phase 3 trials: two with relapsing MS patients — the OPERA I and OPERA II studies (NCT01247324 and NCT01412333), and one in PPMS patients, named ORATORIO (NCT01194570). Based on data from these trials, the FDA approved Ocrevus on March 28, 2017.
However, the research does not stop there. With Ocrevus’ approval, it is necessary to monitor and scrutinize its effectiveness, safety, and tolerability as it begins to be used in clinical practice around the United States.
“People in clinical trials are highly selected for, and so they may not represent the full spectrum of disease that you see in the clinic. So we just want to make sure that what you see in the clinic replicates the findings that you had in clinical trials,” Moss said.
Thus, the Cleveland Clinic researchers decided to assess how Ocrevus was performing at their center, compared to results from the previous three Phase 3 trials.
They ran a prospective longitudinal study — the examination of a group of subjects by assessing treatment outcomes over a period of time — for the tolerability, safety, and effectiveness of Ocrevus in patients treated at the Cleveland Clinic.
The team analyzed 748 patients with a confirmed MS diagnosis, namely a PPMS disease course or relapsing-remitting MS (RRMS). Patients were 18–75 years old, and were followed for at least 6 months before starting treatment with Ocrevus. All participants receive the therapy after its approval.
At ACTRIMS, Moss reported the results of the patients analyzed so far — 274 with RRMS and 76 with PPMS.
Notably, MS patients at the Cleveland Clinic had similar demographic features as those enrolled in the OPERA and ORATORIO trials, which allowed comparisons to be made between the groups.
The real-world patients, however, had differences compared to those analyzed in the Phase 3 trials, namely a longer disease duration (13 versus 7 years), and fewer brain lesions at baseline.
These patients “tended to be older, to have longer disease duration, and they tend to have less active disease at the time they start medication,” Moss said.
Results showed that the most common adverse events of Ocrevus treatment were infusion-related reactions (13%) and infections (12%; mainly primary urinary tract infections and upper respiratory tract infections).
Nine patients (3%) in the Cleveland cohort experienced a serious adverse event, namely “suicidal ideation, depression resulting in hospitalization, Crohn’s colitis, septic abortion, urosepsis, hepatic failure, abdominal pain, infective endocarditis, and basal cell carcinoma,” Moss said.
The rate of adverse events was, however, lower than that reported in the Phase 3 clinical trials for Ocrevus — 7% in the OPERA trials, and 20% in ORATORIO.
The team concluded that “Ocrelizumab is a highly effective treatment for MS,” Moss said, highlighting that the “rates of adverse events are lower than reported in clinical trials.”
Moss, who sees MS patients at the Cleveland Clinic, also emphasized that Ocrevus “has been very successful in a lot of people, and it’s tremendous seeing patients who were not doing well before doing very well now.”