Experimental Medications: Monoclonal Antibodies

Company: Novartis and Genmab

  • Injected subcutaneously, being studied at 20 mg monthly
  • Being studied in RMS

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The Food and Drug Administration (FDA) is conducting a priority review of the cancer medication ofatumumab for the treatment of relapsing forms of MS (RMS). Executives at Novartis, which markets ofatumumab collaboratively with Genmab, say the medication could be approved as early as mid-2020. The European Medicines Agency (EMA), the drug regulatory agency for the European Union, is also reviewing ofatumumab and may approve the medication in early 2021.56

Ofatumumab, a monoclonal antibody used for treating chronic lymphocytic leukemia,12 binds to the CD20 molecule located on the surface of lymphocytes, a type of white blood cell. Lymphocytes are believed to trigger the abnormal immune response that damages the protective sheath (myelin) surrounding nerve cells in the brain and spinal cord. By binding to CD20, the lymphocytes are destroyed and neuronal damage is prevented or delayed.57

This treatment approach is similar to that of ocrelizumab, a monoclonal antibody that is FDA-approved for RMS and primary-progressive MS, as well as rituximab, which is often used off-label to treat MS. But while ocrelizumab and rituximab are administered intravenously, ofatumumab is self-injected subcutaneously (under the skin) once a month. For this reason, ofatumumab could provide the benefits of a CD20 monoclonal antibody with convenient at-home dosing, and could be an option for individuals looking for an alternative to periodic infusions or frequent self-injections.13

The application for FDA approval to use ofatumumab in MS is supported by data from the Phase III ASCLEPIOS I and ASCLEPIOS II trials, in which ofatumumab outperformed Aubagio in slowing disease progression in RMS.56 A total of 1,881 adults with RMS in the two simultaneous trials received a subcutaneous 20-mg injection of ofatumumab plus an oral placebo tablet, or oral Aubagio at 14 mg once daily plus a sham (placebo) injection, for up to 2½ years. Neither the investigators nor the participants knew which treatment was active and which was placebo. Those who received active ofatumumab injections received loading doses of 20 mg upon study entry and then seven and 14 days later before switching to monthly dosing.13

At the end of the two trials, annualized relapse rates were 50.5% and 58.5% lower, respectively, among ofatumumab-treated individuals compared with the Aubagio group (0.11 vs. 0.22) and (0.10 vs 0.25). Those treated with ofatumumab also showed a relative risk reduction of 34.4% in confirmed disability progression (CDP) over three months, and a 32.5% reduced risk of six-month CDP, compared with Aubagio.

Additionally, ofatumumab-treated patients showed fewer gadolinium-enhancing T1 lesions on magnetic resonance imaging compared with those treated with Aubagio, suggesting that ofatumumab suppresses inflammatory activity.56

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