Multiple Sclerosis Society of Canada

Ponesimod

Overview:
  • Also known as: ACT-128800
  • Pharmaceutical Company:Actelion (a Janssen Pharmaceutical Company of Johnson & Johnson)
  • Route and Dose of Administration: Oral (20 mg daily)
  • Type: Sphingosine-1-phosphate receptor 1 (S1P1R) modulator; immunomodulator
  • Emerging Treatment for: Relapsing-Remitting Multiple Sclerosis (RRMS)
  • Status: In Phase III clinical trial
How it Works

Ponesimod works similarly to Gilenya (fingolimod) by acting on certain immune cells called lymphocytes that are involved in attacking the myelin in MS. It binds to the docking site of lymphocytes (T and B cells implicated in the damage caused in the central nervous system in MS) at a specific location called sphingosine-1 phosphate receptor, resulting in a large proportion of lymphocytes to remain in the lymph glands. This results in a decrease in the number of lymphocytes that can reach the brain and spinal cord, leading to reduced damage to myelin on nerve fibers.

Research and Results

Phase II Trial

A phase II , double-blind, placebo-controlled clinical trial recruited 464 people with RRMS to examine the efficacy and safety of ponesimod as a treatment for RRMS. Participants were randomized to receive either 10, 20 or 40 mg dose of ponesimod daily or placebo for 24 weeks. The primary endpoint, measuring a cumulative number of new gadolinium-enhanced lesion from 12-24 weeks, was significantly lower in people taking 10, 20, and 40 mg of ponesimod compared with placebo.

OPTIMUM: Phase III Trial

A phase III randomized, double-blind, multi-center clinical trial called OPTIMUM is testing the efficacy and safety of ponesimod compared with Aubagio (teriflunomide). The trial recruited 1,100 people with RRMS that were given either ponesimod (20 mg) daily or Aubagio (14 mg) daily for 24 weeks. The primary outcome will determine whether ponesimod will significantly reduce the annualized relapse rate (ARR) compared to Aubagio. Other measures include time to confirmed disability accumulation, change in brain volume, and time to first relapse. The results are expected in 2019.

POINT: Phase III Clinical Trial

POINT is a phase III randomized, double-blind, multi-center clinical trial testing the added benefit of taking ponesimod in people that are taking Tecfidera (dimethyl fumarate).The study is recruiting 600 participants that will be randomly assigned to receive either oral ponesimod or placebo daily in addition to Tecifedera. The primary outcome measures changes in annualized relapse rates between the two groups. The study will also measure time to confirmed disability accumulation, time to first relapse, and mean number of combined active lesions. The planned completion date of the trial is in March 2020.

Adverse Effects Reported

In the phase II clinical trial, the most common adverse effects reported were anxiety, dizziness, difficulty breathing (dyspnea), increased liver enzymes, insomnia and swelling of lower legs (peripheral oedema).

References:

Olsson J et al. Oral ponesimod in relapsing–remitting multiple sclerosis: a randomised phase II trial. J Neurol Neurosurg Psychiatry. 2014; 85(11): 1198-208.