NEJM publishes Phase III ASCLEPIOS trials demonstrating superior efficacy of ofatumumab in patients with relapsing multiple sclerosis.- Novartis

Novartis announced that The New England Journal of Medicine (NEJM) published the positive results from the ASCLEPIOS I and II studies evaluating the safety and efficacy of ofatumumab (OMB 157) 20 mg monthly subcutaneous injections versus teriflunomide 14 mg oral tablets taken once daily in adults with relapsing forms of multiple sclerosis (RMS). Both studies met the primary endpoints where ofatumumab showed a significant reduction in the number of confirmed relapses, evaluated as the annualized relapse rate (ARR). Results from the ASCLEPIOS I and II studies showed that compared with teriflunomide, ofatumumab: • Significantly reduced the ARR by 51% (0.11 vs 0.22) and 58% (0.10 vs 0.25) in ASCLEPIOS I and II, respectively (P<.001 in both studies primary endpoints. showed a relative risk reduction of 34 p=".002)" in 3-month confirmed disability worsening cdw and 32 p=".01)" in 6-month cdw in a pre-specified meta-analysis as defined in asclepios disability-related secondary endpoints. showed significant reduction of both gadolinium enhancing gd t1 lesions with a 97 and 94 relative reduction in asclepios i and ii respectively both p><.001), and an 82 and 85 relative reduction in new or enlarging t2 lesions in asclepios i and ii respectively both p><.001) mri-related secondary endpoints. showed superiority in reducing neuroaxonal damage in both studies as measured by neurofilament light chain nfl serum concentrations biomarker secondary endpoint axonal loss which begins at disease onset is a detrimental consequence of central nervous system cns inflammation and is a major determinant of irreversible neurological disability in ms patients. demonstrated a favorable trend in rate of 6-month confirmed disability improvement cdi events but did not reach significance disability-related secondary endpoint. showed the annual rate of brain volume loss was not significantly different mri-related secondary endpoint. demonstrated an overall safety profile similar to teriflunomide the frequency of serious infections and neoplasms was similar across both treatment groups. injection-related reactions nasopharyngitis headache injection-site reactions upper respiratory tract infection and urinary tract infection were the most commonly observed adverse events across both treatment groups occurring in greater than 10 of patients the asclepios studies found that ofatumumab produced a significant reduction in new inflammation as well as fewer clinical relapses and progression events said professor stephen l. hauser director of the ucsf weill institute for neurosciences and co-chair of the steering committee for the asclepios i and ii studies. a separate post hoc analysis demonstrated that nearly 9 out of 10 patients experienced no evidence of disease activity in the second year of treatment. ofatumumab represents a potential new option for rms patients with greater efficacy compared to teriflunomide a comparable safety profile and the convenience of once monthly self-administration without the need for infusions. these data were published in the august 6 2020 issue of the new england journal of medicine. in february the fda and european medicines agency ema accepted the companys supplemental biologics license application sbla and marketing authorization application maa respectively for ofatumumab for the treatment of relapsing forms of multiple sclerosis in adults. if approved ofatumumab will be the first b-cell therapy that can be self-administered at home and has the potential to become a first-choice treatment for use in rms patients. regulatory approval for ofatumumab in the us is expected in september 2020 and in europe by q2 2021. see-hauser s bar-or a cohen j et al. ofatumumab versus teriflunomide in relapsing multiple sclerosis. n engl j med 2020383:546-57.https: www.nejm.org.>