Phase 3 Study to Test Oral Combination, Tecfidera and Ponesimod, to Treat Relapsing MS

Actelion announced that it will investigate the therapeutic potential of a new, oral combination therapy with ponesimod and Tecfidera (dimethyl fumarate) as a treatment for relapsing multiple sclerosis (RMS).

The Phase 3 clinical study, being conducted under a Special Protocol Assessment agreement with the U.S. Food and Drug Administration (FDA), aims to find a combination treatment that has greater efficacy and superior safety, so as to minimize side effects, as a long-term therapy. Preclinical data suggest that the combination of ponesimod and dimethyl fumarate meets both these requirements.

“I have always believed that combination therapy is the future for the treatment of relapsing multiple sclerosis. The properties of ponesimod, supported by our preclinical knowledge and clinical results, all point towards ponesimod being ideally suited for use in combination. I am very excited that we’ve gained agreement with health authorities on this innovative approach, and I look forward to Actelion generating the data that could change the treatment paradigm in this devastating disorder,” Jean-Paul Clozel, MD, Actelion’s chief executive officer, said in a press release.

Actelion launched a Phase 3 clinical program in RMS in April 2015, with the OPTIMUM clinical trial (NCT02425644) — a superiority study comparing the efficacy and safety of ponesimod with that of Aubagio (teriflunomide). The decision to move into Phase 3 development was grounded on the Phase 2b dose-finding study (NCT01093326) with ponesimod in patients with relapsing-remitting multiple sclerosis (RRMS).

Ponesimod is an orally active, selective sphingosine-1 phosphate receptor 1 (S1P1) immunomodulator. The drug can prevent immune lymphocytes from leaving lymph nodes, thereby reducing circulating blood lymphocyte counts and preventing infiltration of lymphocytes into target tissues.

Initial trial results suggested that ponesimod does not cause lymphotoxicity by destroying lymphocytes or interfering with their cellular function, and it does not affect other immune system cells.

The new clinical trial, called  POINT (PonesImod aNd Tecfidera) (NCT02907177), is designed to evaluate the efficacy, safety and tolerability of add-on therapy with ponesimod (20 mg) against placebo in adults with active RMS who are receiving treatment with Tecfidera.

This prospective, multicenter, double-blind and parallel-group superiority study will enroll nearly 600 patients starting, most likely, by the end of the year. More information is available on the study’s clinical trials.gov webpage, or by clicking on the trial’s identification number above.

Participants will receive Tecfidera two times a day for at least six months, and be randomized (ratio of 1:1) to also receive either ponesimod 20 mg or placebo once a day. Treatment will continue until the last participant receives treatment for 60 weeks – the trial’s average treatment duration is about two years, with a maximum of three years.

Primary objectives include assessing if an add-on therapy with ponesimod can effectively reduce relapse frequency, versus placebo, in RMS patients under Tecfidera treatment. Secondary objectives include evaluating the combination therapy’s efficacy, safety and tolerability profile.

The trial’s primary endpoint is the assessment of the annualized relapse rate (ARR), defined as the number of confirmed relapses per patient, per year, from randomization until the end of the trial. Corresponding safety and efficacy endpoints include the time to 12 weeks confirmed disability accumulation (CDA), and safety endpoints include the time to 12 weeks CDA and adverse events leading to premature discontinuation of treatment.

The company will provide an update on the program during its quarterly investor conference call, set for Oct. 20.

“Our clinical development program for ponesimod in multiple sclerosis was already innovative when we decided to move into Phase III. OPTIMUM is the first study in MS to target superiority over a commercialized oral therapy. It also includes a number of patient oriented outcome assessments. With POINT, the first trial in active RMS adding one oral drug to another, we will assess the clinical utility of combination therapy with ponesimod, to offer patients better control of their disease,” said Guy Braunstein, MD, Actelion’s head of Global Clinical Development.