Now that Johnson & Johnson (J&J), through its Janssen Pharmaceuticals unit, has won the FDA’s nod for Ponvory (ponesimod), market factors will decide how the once-daily oral selective sphingosine-1-phosphate receptor 1 (S1P1) modulator fares against several others already approved in the class.
Ponvory won U.S. regulators’ blessing to treat adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. The green light comes almost exactly a year after J&J submitted the data package for FDA review. Wainwright analyst Raghuram Selvaraju said in a report at the time that Ponvory “could be in the vanguard of this category given the strength of the efficacy data observed to date.”
The new MS entry is one of two late-stage assets acquired in New Brunswick, N.J.-based J&J’s 2017 buyout of Actelion Ltd., of Allschwil, Switzerland, for $30 billion, and it’s entering the market as the fourth S1P1 receptor modulator indicated for relapsing MS, facing off with entrenched market leader Gilenya (fingolimod), from Basel, Switzerland-based Novartis AG, which posted 2019 sales of $3.2 billion, as well as newer entrants Mayzent (siponimod), also from Novartis, approved in 2019 with a broad label including relapsing forms of MS to secondary progressive MS, and Zeposia (ozanimod), which New York-based Bristol Myers Squibb Co. picked up in its acquisition of Celgene Corp., of Summit, N.J., and moved across the FDA finish line in March 2020. Cortellis analysis predicts full-year sales of Ponvory totaling $368 million by 2025.
Ponvory’s go-ahead is based, in part, on a two-year, head-to-head phase III study in which Ponvory at the 20-mg dose turned up superior efficacy in significantly reducing annual relapses by 30.5% compared to Aubagio (teriflunomide, Sanofi SA) 14 mg in patients with relapsing MS. Over the study period, 71% of patients treated with Ponvory recorded no confirmed relapses, compared to 61% in the Aubagio group, and the drug proved better than Aubagio in reducing the number of new gadolinium-enhancing (GdE) T1 lesions and the number of new or enlarging T2 lesions by 59% and 56%, respectively. GdE T1 lesions and T2 lesions are identified using magnetic resonance imaging technology and are recognized as classic measures of MS pathology.
Ponvory also prevented disability from getting worse for most people. Specifically, nine in 10 patients did not have worsening of three-month disability, and Ponvory achieved a numerical benefit in delaying progression, although the difference in rates of disability progression was not statistically significant between the Ponvory and Aubagio groups.
Target’s Arena even wider
If treatment needs to be stopped, Ponvory leaves the blood within one week, J&J noted, with effects on the immune system wearing off in one to two weeks for most patients – a setup that could provide an edge over competitors and help with treatment strategy if patients need to receive vaccines, address potential infections, or begin family planning. The drug has no known food restrictions and requires no genetic testing or first-dose monitoring for most patients. It’s been generally well-tolerated over multiple clinical studies totaling more than 10 years, with overall adverse event (AE) rates similar to placebo in the phase II trials and to Aubagio in phase III, J&J said. The most common AEs to surface in Ponvory patients during the phase III experiment were upper respiratory infection, abnormal liver tests and hypertension.
Inhibiting S1P1 protein activity is believed to reduce the number of circulating lymphocytes that can cross the blood-brain barrier. In patients with MS, that movement of immune cells into the brain causes damage to the myelin sheath, resulting in the signs and symptoms of the disease. An estimated 1 million adults in the U.S. are currently living with MS, and roughly 85% are initially diagnosed with relapsing MS.
Idorsia Pharmaceuticals Ltd., the firm spun out of the J&J acquisition of Actelion with the latter’s early clinical and R&D programs, stands to collect quarterly payments of 8% of the net sales of Ponvory under the terms of a revenue-sharing agreement. In the first quarter of last year, Janssen submitted ponesimod for approval in Europe, where it’s still under review.
Ponvory’s target is drawing interest against other indications. San Diego-based Arena Pharmaceuticals Inc. has etrasimod, a candidate designed for optimized pharmacology and engagement of S1P receptors 1, 4 and 5, which may lead to an improved efficacy and safety profile. The drug provides systemic and local effects on specific immune cell types and has the potential to treat multiple immune-mediated inflammatory diseases, including ulcerative colitis (UC), Crohn’s disease (CD), atopic dermatitis (AD) and alopecia areata, Arena said. In January, the etrasimod Elevate UC 52 phase II trial in ulcerative colitis UC completed enrollment. That experiment and phase III Elevate UC 12 study are on track for top-line data in the first quarter of next year. In February, the company dosed its first participant in the phase IIb Voyage trial in eosinophilic esophagitis. In November 2020, the etrasimod AD phase IIb trial called Advise delivered top-line data, and Arena is moving into a phase III registrational program.
Wainwright’s Patrick Trucchio pointed in a March 3 report to a “significant data release expected later in 2021 on a phase II trial [called Cultivate], evaluating etrasimod in CD, an indication where, if etrasimod is successful, [it] could have blockbuster potential, by our estimates.”
The MS space is becoming more crowded. Novartis recently launched its anti-CD20 monoclonal antibody Kesimpta (ofatumumab), approved last summer and self-administered once monthly using an autoinjector pen. Another CD20 player coming on strong is Ocrevus (ocrelizumab), from Roche Holding AG, also of Basel, Switzerland. Not to be overlooked is the CD20 bid from New York-based TG Therapeutics Inc., which said last December that two phase III studies of ublituximab met their primary endpoints of significantly reducing the annualized relapse rate in MS. The company estimated it would file a BLA in the middle of 2021