dm+d

40240711000001108

New Medicines

PonvoryRelapsing-remitting multiple sclerosis (MS)

Information

Ponvory
New molecular entity
Janssen-Cilag
Janssen

Development and Regulatory status

Launched
Approved (Licensed)
Launched
October 2021
Oct 21Ponvory oral tablets available in the UK. Initiation pack contains 24 tablets various strengths =£536.99; treatment pack contains 28 x 20mg tablets =£1073.97 [21].
Sep 21Launched in US [23].
Jul 21Licensed in UK [19].
May 21Approved in EU [18]
Mar 21Recommended for EU approval by CHMP - the full indication is "for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features." The medicine should be initiated under the supervision of a physician experienced in the management of multiple sclerosis [16].
Mar 21FDA has approved ponesimod for the treatment of adult patients with relapsing multiple sclerosis [15]
Mar 20Janssen submits NDA to the U.S. Food and Drug Administration for ponesimod for the treatment of adult patients with relapsing multiple sclerosis [13].
Mar 20Janssen have submitted a MAA to the European Medicines Agency (EMA) seeking approval for ponesimod for the treatment of adult patients with relapsing multiple sclerosis (MS) [12].
Jun 19Filings planned for 2017-2021 [7].
May 19Filings planned for 2019 [11].
Jan 17OPTIMUM (NCT02425644) study recruiting, estimated primary completion date now February 2019; POINT (NCT02907177) add-on treatment to dimethyl fumarate not yet recruiting [6].
May 14PIII study is planned. Actelion does not plan to advance ponesimod to PIII trials until a development partner has been found [2].
Janssen expects FDA decision for the treatment of MS by end of 2020 [14].

Category

Oral selective sphingosine-1 phosphate-1 receptor agonist
In England and Wales the annual incidence and prevalence of MS is 3.5-6.6 and 100-120 per 100,000, respectively. Around 80% have relapsing-remitting disease at onset.
Relapsing-remitting multiple sclerosis (MS)
Oral

Further information

Yes

Trial or other data

Feb 22NICE guidance published. Ponesimod is recommended for treating relapsing–remitting multiple sclerosis with active disease defined by clinical or imaging features in adults, only if the company provides ponesimod according to the commercial arrangement. [22]
Oct 21Draft NICE guidance does not recommend ponesimod because cost-effectiveness estimates are uncertain and above what NICE normally considers an acceptable use of NHS resources [20].
Mar 21PIII OPTIMUM study (n=1133) is published; ponesimod was associated with lower annualised relapse rate (−30.5%), Fatigue Symptom and Impact Questionnaire–Relapsing MS symptom score (−3.57) and combined unique active lesions on magnetic resonance imaging (−56%) compared to teriflunomid [17].
Jul 19Top-line data from PIII OPTIMUM study has shown ponesimod has met its primary end point, annualised relapse rate (ARR) up to the end of the study. The study was designed to demonstrate superiority of ponesimod 20mg versus teriflunomide 14mg. One of the key secondary end points was change in fatigue-related symptoms from baseline to week 108. [9,10].
Mar 18PIII POINT study is recruiting & due to complete collection of primary outcome data in Mar 20. PIII OPTIMUM has finished recruiting & expects to complete collection of primary outcome data in Apr 19 [8].
Jan 17OPTIMUM study expected primary completion now Feb 2019; a further PIII study, POINT (NCT02907177) will examine the efficacy of ponesimod compared to placebo in patients with active relapsing MS who are being treated with dimethyl fumarate; primary outcome is annualised relapse rate to 3.3 years, estimated recruitment 600, and estimated primary completion date March 2020 [6].
Jan 16NCT02425644=PIII OPTIMUM study. Expected completion date May 18 [5]
Apr 15Actelion begins a PIII study of ponesimod for MS, which will recruit 1,100 patients [4].
Apr 15The PIII study, OPTIMUM, is a multicenter, randomized, double-blind, parallel-group, active-controlled superiority study to compare the efficacy and safety of ponesimod to teriflunomide in subjects with relapsing MS. The study aims to determine whether ponesimod is more efficacious than teriflunomide in reducing relapses. The study is expected to enroll approximately 1,100 subjects, randomized in 2 groups in a 1:1 ratio to receive ponesimod 20 mg/day or teriflunomide 14 mg/day, and is expected to last a little over 3 years [4].
Mar 15NCT01093326 is a PII extension study. It is on-going and not due to complete until 2022. PIII development has not started [3].
Aug 11Positive data from placebo-controlled PIIb dose-finding 24-week study of ponesimod 10mg, 20mg or 40mg in 464 pts with RR-MS. Ponesimod significantly reduced the cumulative number of new active lesions on monthly MRI brain scans performed from weeks 12 to 24 (main outcome). The average lymphocyte counts were reduced in a dose-dependent fashion and returned to baseline values within a week in patients who discontinued treatment with ponesimod. There were a small overall number of confirmed relapses and also a clinically meaningful effect observed on annualised relapse rate. [1]

Evidence based evaluations