Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) will review Novartis‘ applications seeking regulatory approval of ofatumumab, an investigational B-cell therapy for the treatment of relapsing forms of multiple sclerosis (MS) in adults.
Novartis’ applications for ofatumumab — which has the potential to become a first-choice treatment for relapsing MS patients, easily self-administered using an autoinjector pen — were accepted by both the U.S. and EU regulatory agencies.
The FDA’s decision is expected by June 2020, with the EMA’s decision likely by 2021.
Ofatumumab is a fully human monoclonal antibody — a lab-made immunotherapy that can bind to specific proteins in the body — against CD20, a marker present on immune B-cells involved in MS development. The therapy works by binding to the CD20 protein in certain B-cells, leading to the cells’ depletion. This is thought to reduce inflammation in the central nervous system, comprised of the brain and spinal cord.
The key difference with Ofatumumab is that it would be a self-administered, once-monthly therapy using an autoinjector pen. The therapy under development is a 20 mg under-the-skin (subcutaneous) injection.
“We are excited that ofatumumab has the potential to be a powerful first-choice treatment option for patients and physicians looking for an impactful intervention,” Krishnan Ramanathan, head of the neuroscience global program at Novartis, said in a press release.
Unlike the more common FDA application for an investigational new drug, or IND, a BLA covers a biologic product — a treatment that comes from a natural source, be it human, animal, or microorganism. Produced by biotechnology methods or other cutting-edge technologies, biologics can be composed of sugars, proteins, or nucleic acids, or a complex combinations of these substances, or may be living entities such as cells and tissues. This is in contrast to most medications, which are chemically synthesized with a known structure.
The applications seeking the approval of ofatumumab were based on the positive results of two Phase 3 trials: ASCLEPIOS I (NCT02792218) and II (NCT02792231). These trials compared the efficacy and safety of ofatumumab versus Aubagio (teriflunomide; marketed by Sanofi Genzyme) in adults with relapsing MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).
The ASCLEPIOS trials enrolled a total of 1,882 patients — 927 in ASCLEPIOS I and 955 in ASCLEPIOS II — ages 18–55, across 37 countries. The individuals had no-to-mild disability per the Expanded Disability Status Scale, or EDSS, with scores of 0–5.5.
The participants were randomly assigned to receive either ofatumumab 20 mg injections once a month, or oral Aubagio 14 mg capsules once daily together with placebo injections for up to 30 months (about 2.5 years).
The results showed that ofatumumab was superior to Aubagio in reducing the annualized relapse rate, which was the trials’ primary endpoint. Patients treated with ofatumumab had an annualized relapse rate of 0.11 in ASCLEPIOS I and 0.10 in ASCLEPIOS II, compared with rates of 0.22 (ASCLEPIOS I) and 0.25 (ASCLEPIOS II) in the Aubagio group.
This meant that ofatumumab led to a more than 50% decrease in relapse rate, compared with Aubagio. The data also showed that ofatumumab led to a more than 90% reduction in active brain lesions, representing a marked effect on inflammatory activity.
The trials’ secondary endpoints included confirmed disability worsening at three and six months. The results showed that ofatumumab significantly reduced both these parameters — relative risk reduction of 34.4% at three months, and 32.5% at six months, compared with Aubagio.
“With ofatumumab, we underpin our relentless dedication to reimagine medicine for patients across the MS spectrum, and will work closely with the regulatory authorities to ensure it is available for people living with MS as soon as possible,” Ramanathan said.
Novartis also announced the completion of its Phase 2 APLIOS study. This 12-week, open-label study assessed whether ofatumumab’s therapeutic activity is equivalent if it’s administered using a pre-filled syringe — like the one used in the ASCLEPIOS trials — or an autoinjector pen.
The results showed that ofatumumab can be self-administered at home using a patient-friendly autoinjector pen. These results will be shared in a poster, titled “Onset Of B-cell Depletion With Subcutaneous Administration Of Ofatumumab In Relapsing Multiple Sclerosis: Results From The APLIOS Bioequivalence Study.” The poster will be presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020, taking place in West Palm Beach, Fla., Feb. 27-29.
Ofatumumab was initially developed by the Danish biotech company Genmab and GlaxoSmithKline (GSK). Novartis acquired the rights to ofatumumab in 2015. Under the brand name Arzerra, ofatumumab is already approved in the U.S. to treat certain leukemias.
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