Janssen's Oral S1P1 Modulator Ponvory (ponesimod) Receives FDA Approval for Relapsing Multiple Sclerosis, Demonstrating Superior Efficacy Over Aubagio

Mar 29, 2021 03:28 CST Updated Mar 20, 00:28

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March 19, 2021/BioValleyBIOON/--Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced that the U.S. Food and Drug Administration (FDA) Ponvory (ponesimod) has been approved. This once-daily, oral, selective sphingosine-1-phosphate receptor 1 (S1P1) modulator is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS). Regarding administration, Ponvory does not require genetic testing or first-dose cardiac monitoring for most patients. However, as initiation of Ponvory therapy may lead to a decrease in heart rate, first-dose monitoring is recommended for patients with a specific history of cardiac disease.

It is worth noting that,Ponvory isFDAThe first and only approved oral disease-modifying therapy to conduct a controlled study against an existing marketed oral therapy.Compared with Aubagio (Chinese brand name: Aobajie; generic name: teriflunomide), the currently available oral MS medication on the market, Ponvory has demonstrated superior efficacy in reducing the annualized relapse rate (by nearly one-third). Moreover, its efficacy and safety have been substantiated by more than 10 years of cumulative clinical research data.

Aubagio is an oral medication from Sanofi, which was approved in the United States as early as September 2012.FDAApproved for the treatment of relapsing multiple sclerosis (RMS), this drug is an industry-leading oral MS medication that has been marketed in more than 70 countries and regions worldwide. In China,Aubagio (teriflunomide) was approved for marketing in July 2018, becoming the first oral disease-modifying therapy approved in China for the treatment of multiple sclerosis.

In the United States, there are nearly 1 million adult patients with multiple sclerosis (MS), approximately 85% of whom initiallyDiagnosisThe patient was diagnosed with relapsing multiple sclerosis (MS). Despite progress made in recent years, there remains an unmet medical need in this field. Compared with currently available therapies, Ponvory has demonstrated superior efficacy, particularly in reducing new inflammatory lesions and disability accumulation. The approval of Ponvory for market launch will provide patients with an important new oral medication.

This approval is based on the results of the head-to-head Phase III OPTIMUM study (NCT02425644). The study was conducted in adult patients with RMS, comparing the efficacy, safety, and tolerability of ponesimod with Aubagio.

Notably, the OPTIMUM study is the first large-scale, controlled, head-to-head study comparing two oral therapies for RMS. The data demonstrated that ponesimod (20 mg, once daily) was superior to Aubagio (14 mg, once daily) with respect to the primary endpoint and multiple secondary endpoints.

Specific data are as follows: (1) Regarding the primary endpoint, from baseline to Week 108 of treatment, the annualized relapse rate (ARR) was statistically significantly reduced by 30.5% in the ponesimod group compared with the Aubagio group (ARR: 0.202 vs. 0.290; p=0.0003). During the study period, 71% of patients in the ponesimod group remained free of confirmed relapses, compared with 61% in the Aubagio group. (2) Ponesimod was also superior to Aubagio in reducing the number of new gadolinium-enhancing (GdE) T1 lesions and new or enlarging T2 lesions, with reductions of 59% and 56%, respectively. GdE T1 lesions and T2 lesions were identified via magnetic resonance imaging (MRI) and are considered classic markers of relapse in multiple sclerosis (MS) pathology, providing insights into disease activity and disease burden, respectively. (3) The safety profile of ponesimod observed in this study was consistent with that reported in previous studies and with the known safety profiles of other sphingosine-1-phosphate (S1P) receptor modulators. The most common treatment-emergent adverse events (TEAEs) in the ponesimod group were elevated alanine aminotransferase (ALT), nasopharyngitis, headache, and upper respiratory tract infection.

Multiple Sclerosis (MS) is a chronic central nervous systemAutoimmunityMultiple sclerosis is an inflammatory demyelinating disease that affects 2.3 million people worldwide, with a higher prevalence in women than in men. The disease is characterized by demyelination and axonal loss, leading to neurological impairment and severe disability. The main subtype of MS is relapsing multiple sclerosis (RMS), which accounts for 85% of MS patients and includes clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS). A relapse is defined as the onset of new, worsening, or recurrent neurological symptoms lasting more than 24 hours, in the absence of fever or infection. Relapses may fully resolve within days or weeks, or they may result in persistent deficits and the accumulation of disability.

The active pharmaceutical ingredient of Ponvory is ponesimod, a novel, oral, selective sphingosine-1-phosphate receptor 1 (S1P1) modulator that functionally inhibits S1P protein activity and sequesters lymphocytes within lymph nodes, thereby reducing the number of circulating lymphocytes capable of crossing the blood-brain barrier. In patients with multiple sclerosis (MS), lymphocytes enter the brain and damage myelin. Myelin is a protective sheath that insulates nerve cells. Damage to myelin can slow or halt nerve conduction, resulting in the neurological symptoms and signs of multiple sclerosis.

Currently, sphingosine-1-phosphate (S1P) receptors have become an important target for new drug development in the field of multiple sclerosis (MS). In March 2019,NovartisThe oral S1P receptor modulator Mayzent (siponimod) has been approved by the U.S. FDA for the treatment of adult patients with RMS. In March 2020, the oral S1P receptor modulator Zeposia (ozanimod), from Celgene (acquired by Bristol-Myers Squibb), received U.S.FDAApproved for the treatment of adult patients with RMS.

Following its market launch, Ponvory will compete directly with Mayzent and Zeposia. In addition, Ponvory faces competition from several other oral medications, such asNovartisGilenya from Novartis, Aubagio from Sanofi, Tecfidera and Vumerity from Biogen, Mavenclad from Merck, and Ocrevus, an antibody drug from Roche requiring only two infusions per year. (Bioon.com)

Original Source: Janssen Announces U.S.FDA approval of PONVORY™ (ponesimod), an Oral Treatment for Adults with Relapsing Multiple Sclerosis Proven Superior to Aubagio® (teriflunomide) in Reducing Annual Relapses and Brain Lesions