Other names: ACT-128800, Ponvory
Ponesimod (Ponvory) is a new drug treatment under investigation for relapsing remitting multiple sclerosis (MS). It is taken as a tablet once daily.
Ponesimod for relapsing remitting MS: Appraisal
Ponesimod is a new drug treatment under investigation for relapsing remitting multiple sclerosis (MS). It is taken as a tablet once daily.
- Ponesimod causes lymphocytes to be retained in lymph glands
- In phase III relapsing remitting MS studies, ponesimod reduced relapse rate by 30% compared to Aubagio
- In a phase III study, the most frequent side effects included nasopharyngitis (common cold), headache, chest infections and an increase in liver enzymes
Licensing and appraisal
The Medicines and Healthcare products Regulatory Agency (MHRA) is currently reviewing licensing for ponesimod in England, Scotland and Wales.
The European Medicines Agency has recommended that ponesimod should be granted a licence for people with active relapsing remitting MS. Active is defined as people who are having relapses or evidence of MS activity on MRI scans. The next step in the approval process is for the European Commission to grant the licence, taking into account the EMA's recommendation. The EC licence will cover Northern Ireland.
NICE is carrying out an appraisal of ponesimod for relapsing remitting MS. In its draft recommendation, NICE does not recommend ponesimod as an NHS treatment in England and Wales. The MS Trust will be challenging the recommendation. If you wish to comment on this initial decision, you can do so through the NICE website by 5pm, 26 October 2021. The NICE appraisal committee will meet again to review all the comments received and expects to publish its final decision later this year.
The Scottish Medicines Consortium will carry out a separate appraisal of ponesimod.
How does ponesimod work?
Ponesimod belongs to the same class of drugs as Gilenya (fingolimod). It acts on certain types of white blood cells (lymphocytes) which are involved in the autoimmune attack on myelin seen in MS. It binds to special locations (or receptors) on the surface of the lymphocytes, called sphingosine-1-phosphate receptors (S1P-R). This causes a larger proportion of lymphocytes to be retained in the lymph glands. The number of activated lymphocytes reaching the brain is decreased, resulting in reduced immune attack on nerve cells in the brain and spinal cord.
How is ponesimod taken?
Ponesimod is taken as a tablet, once daily.
What are the results so far?
In a phase II study, 464 people with relapsing remitting MS took one of three doses of ponesimod or placebo for 24 weeks. The main measure was the number of new active lesions seen on MRI. Daily doses of 10, 20 and 40 mg ponesimod reduced the number of lesions by 43%, 83% and 77% compared to placebo. The highest dose of ponesimod reduced relapses by 52% compared to placebo.
- OPTIMUM - ponesimod compared to Aubagio (teriflunomide)
This phase III study recruited 1133 participants with relapsing MS who took either ponesimod, or Aubagio once daily for 2 years. Those on ponesimod experienced a 30% reduction in relapse rate, 56% reduction in active lesions, and a statistically significant improvement in fatigue symptoms compared to Aubagio. There was a trend toward less disability progression on ponesimod, but this was not statistically different to Aubagio.
- POINT - ponesimod combined with Tecfidera (dimethyl fumarate)
This phase III study is recruiting 600 participants with active relapsing MS who will take either ponesimod or placebo in addition to Tecfidera for at least 60 weeks. The main aim of the study is to assess whether the combination of ponesimod and Tecfidera is more effective than Tecfidera alone at reducing the number of relapses. The study will also measure disability progression, effect on brain volume, time to first relapse, disease activity observed on MRI scans, fatigue, and adverse events.
This study has been terminated because of low recruitment rates.
Further details of this study.
The most common side effects reported in the phase II study were anxiety, dizziness, breathlessness, raised liver enzymes, influenza, sleeplessness and peripheral oedema (swelling of lower legs). In the Optimum study, the most frequent side effects included nasopharyngitis (common cold), headache, chest infections and an increase in liver enzymes measured in the blood. Seizures and macular oedema (swelling at the back of the eye) occurred more frequently in those taking ponesimod.
Like Gilenya, ponesimod causes an initial temporary slowing of heart rate. This has been minimised in clinical trials by starting people on low doses of ponesimod and gradually increasing over several days.
- J Neurol Neurosurg Psychiatry. 2014 85(11):1198-208. Read the full paper Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial.
- JAMA Neurol. 2021;78(5):558-567 Read the full paper Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 OPTIMUM study: A randomized clinical trial.