SUMMARY:
- Top-line results were announced from a Phase 3 study comparing oral ponesimod (The Janssen Pharmaceutical Companies of Johnson & Johnson) to Aubagio® (teriflunomide, Sanofi Genzyme).
- According to a company press release, the study met primary and most secondary endpoints, significantly reducing the annual relapse rate in adults with relapsing MS.
- Side effects were said to be similar to those reported from previous studies of ponesimod and for this class of therapy. These include potential to cause a temporary slowing of heart rate, anxiety, dizziness, breathlessness, raised liver enzymes, influenza, sleeplessness and swelling of the lower legs.
- Further details will be presented at the 2019 Congress of the European Committee for Treatment and Research in MS in September. A second Phase 3 trial is underway, and the company plans to apply to the U.S. Food and Drug Administration seeking approval to treat relapsing MS later this year.
DETAILS
Background: Multiple sclerosis involves an immune system attack on the brain and spinal cord. Ponesimod is a compound that binds to a docking site (sphingosine-1-phosphate receptor 1, or S1P
1 receptor) on immune cells, including T cells and B cells (lymphocytes) that have been implicated in causing nervous system damage in MS. The pill induces immune cells to remain in lymph nodes, inhibiting their migration into the brain and spinal cord. Similar therapies are approved by the FDA to treat MS—Gilenya
® fingolimod, Novartis International AG) and Mayzent
® (siponimod, Novartis International AG), and one is under review by the FDA (ozanimod, Celgene Corporation). In an earlier phase II study in people with MS, ponesimod significantly reduced disease activity seen on MRI scans (
Journal of Neurology, Neurosurgery and Psychiatry 2014 Nov; 85(11): 1198–1208).
The Study: Participants were randomly assigned to receive oral ponesimod 20 mg once daily or teriflunomide 14 mg once daily for 108 weeks. The primary outcome that was measured was the rate of relapses. Secondary endpoints included fatigue, disease activity on imaging scans, and disability accumulation.
Results: According to a company press release, the study met primary and most secondary endpoints, significantly reducing the annual relapse rate in adults with relapsing MS. Side effects were said to be similar to those reported from previous studies of ponesimod and for this class of therapy. These include potential to cause a temporary slowing of heart rate, anxiety, dizziness, breathlessness, raised liver enzymes, influenza, sleeplessness and swelling of the lower legs. Also in phase 2 studies, an initial temporary slowing of heart rate was minimized by starting people on low doses and gradually increasing over several days.
Conclusions: Further details will be presented at the 2019 Congress of the European Committee for Treatment and Research in MS in September. A second phase 3 study is ongoing, evaluating ponesimod in people with MS who are still experiencing relapses while taking Tecfidera
® (dimethyl fumarate, Biogen, Inc.).
The company plans to submit an application to the U.S. Food and Drug Administration seeking approval to treat relapsing MS later this year.
Aubagio is a registered trademark of Sanofi Genzyme
Mayzent is a registered trademark of Novartis International AG
Gilenya is a registered trademark of Novartis International AG
Tecfidera is a registered trademark of Biogen