Johnson & Johnson's Oral S1P1 Modulator Ponvory (Ponesimod) Approved by European Commission: Demonstrates Superior Efficacy Over Sanofi's Aubagio in Relapsing Multiple Sclerosis

May 28, 2021 /BioonBIOON/ -- Janssen Pharmaceuticals, a Johnson & Johnson (JNJ) company, recently announced that the European Commission (EC) has approved Ponvory (ponesimod), a once-daily, oral, selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features. Multiple sclerosis (MS) is an unpredictable and complex disease that varies significantly in its presentation among individuals, placing a heavy burden on patients and their loved ones. This approval will provide a new oral treatment option for the adult RMS patient population in Europe.

In the United States, Ponvory was approved in March 2021 for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), 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, because initiation of Ponvory therapy can cause a decrease in heart rate, first-dose monitoring is recommended for patients with certain preexisting cardiac conditions.

Data from the Phase III OPTIMUM study show,Compared with the currently widely used first-line oral standard-of-care drug Aubagio (Chinese brand name: Aobaojie; generic name: teriflunomide), Ponvory demonstrated superior efficacy in reducing the annualized relapse rate (a 30.5% reduction in the annualized relapse rate, p < 0.001)., and over 10 years of cumulative clinical research data have demonstrated its efficacy and safety.

Aubagio is an oral medication from Sanofi that was approved in the United States in September 2012 and in the European Union in August 2013, respectively, for the treatment of relapsing forms of multiple sclerosis (RMS). As an industry-leading oral MS drug, it has been marketed in over 70 countries and regions worldwide. In China, Aubagio (Aobajie) was approved in July 2018, becoming the first oral disease-modifying therapy (DMT) approved in China for the treatment of multiple sclerosis.

Multiple sclerosis (MS) is a chronicAutoimmunityinflammatory disease characterized by demyelination and axonal loss, leading to neurological damage and severe disability. Despite advances in recent years, an unmet medical need persists in this field. Compared with currently marketed therapies, Ponvory demonstrates superior efficacy, particularly in reducing new inflammatory lesions and disability accumulation. Upon market launch, Ponvory will provide an important new oral treatment option for patients with relapsing multiple sclerosis (RMS).

This EU 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 versus Aubagio.

Notably, the OPTIMUM study is the first head-to-head comparison of two oral disease-modifying therapies (DMTs) in RMS. Data demonstrated that ponesimod (20 mg, once daily) exhibited superiority over Aubagio (14 mg, once daily) across both the primary endpoint and multiple secondary endpoints of the study.

The specific data are as follows: (1) For the primary endpoint, from baseline to Week 108 of treatment, the annualized relapse rate (ARR) in the ponesimod group was statistically significantly reduced by 30.5% compared with the Aubagio group (ARR: 0.202 vs. 0.290, p=0.0003). (2) For the key secondary endpoint, based on the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) scores at Week 108, fatigue symptoms in the ponesimod group were statistically significantly reduced compared with the Aubagio group (mean difference: -3.57, p=0.0019). (3) For other secondary endpoints, the number of combined unique active lesions (CUAL) in the brain was significantly reduced by 56% in the ponesimod group compared with the Aubagio group (p<0.0001). (4) The safety profile of ponesimod observed in this study was consistent with that reported in previous studies and with other known 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, Image source: medgadget.com)

Multiple sclerosis (MS) is a chronic disease of the central nervous systemAutoimmunityMultiple sclerosis (MS) is an inflammatory disease affecting 2.3 million people worldwide, with an incidence rate three times higher in women than in men. The disease is characterized by demyelination and axonal loss, leading to neurological impairment and severe disability. Relapsing forms of MS include clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS, accounting for 85% of all MS cases), and secondary progressive multiple sclerosis (SPMS). MS is one of the most common causes of neurological disability in young and middle-aged adults. Although incidence rates vary worldwide, they are highest in Europe and North America.

The symptoms of relapsing multiple sclerosis (RMS) vary from person to person and may change or fluctuate over time. In addition to many common visible symptoms, there are invisible symptoms that patients with MS may find difficult to describe, yet which can significantly impact their overall emotional well-being and social functioning, such as pain, fatigue, or numbness. A relapse is defined as new, worsening, or recurring neurological symptoms lasting more than 24 hours in the absence of fever or infection. Relapses may resolve completely within days or weeks, or lead to persistent impairment 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 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), the infiltration of lymphocytes into the brain damages myelin. Myelin is a protective sheath that insulates nerve cells. Damage to myelin can slow or block 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 MS. In March 2019,NovartisThe oral S1P receptor modulator Mayzent (siponimod) was 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.

Upon market launch, Ponvory will compete directly with Mayzent and Zeposia. In addition, Ponvory will also face competition from several other oral therapies, such asNovartisGilenya, Sanofi's Aubagio, Biogen's Tecfidera and Vumerity, Merck's Mavenclad, and Roche's Ocrevus, an antibody drug requiring only two infusions per year. (Bioon.com)

Original Source: European Commissionapproves PONVORYTM (ponesimod), a Once Daily, Oral Therapy for the Treatment of Adults with Relapsing Forms of Multiple Sclerosis with Active Disease Defined by Clinical or Imaging Features