Novartis’ Kesimpta Reduces Risk of Relapse-Independent Disability Progression by Nearly 60% in Newly Diagnosed RMS Patients

April 18, 2021 News /Bio ValleyBIOON/ --Novartis(Novartis) recently announced new post hoc analysis data from the Phase III ASCLEPIOS trial at the 73rd Annual Meeting of the American Academy of Neurology (AAN) in 2021. The data showed that, in the subgroup of patients with newly diagnosed, treatment-naïve relapsing multiple sclerosis (RMS), when used as first-line therapy, compared with Aubagio (teriflunomide),Kesimpta (ofatumumab) reduced the risk of disability progression independent of relapse activity (PIRA) by nearly 60% at 3 and 6 months.

Kesimpta is the first targeted B-cell therapy that can be easily administered at home, with patients self-administering subcutaneous injections once a month. Aubagio is an oral medication from Sanofi, a commonly used first-line treatment for multiple sclerosis (MS) and a leading oral disease-modifying therapy for MS in the industry.

In newly diagnosed, treatment-naïve RMS patients, more than 50% of confirmed disability worsening events were PIRA, an emerging endpoint used in MS trials to measure disability worsening unrelated to relapses, indicating that disease progression begins early on. TheseNew data further support Kesimpta as the preferred treatment option for adult patients with RMS.

Furthermore, open-label extension study data from the ALITHIOS trial demonstrated that subcutaneous administration of Kesimpta maintained patients’ mean serum IgM/IgG levels within the reference range over a 3-year period through December 2002.

“PIRA analysis shows that more than half of the disability worsening events experienced by patients with early relapsing multiple sclerosis (RMS) occur independently of whether they have experienced a relapse,” said Jacqueline A. Nicholas, MD, Director of Neuroimmunology at the Multiple Sclerosis (MS) Center of Riverside Methodist Hospital in Ohio, USA. “Compared with Aubagio, Kesimpta reduced the risk of progression by nearly 60%, reinforcing the importance of early intervention and high-efficacy therapy to address underlying disease progression before irreversible damage occurs.”

NovartisEstelle Vester Blokland, Global Head of Neuroscience Medical Affairs, stated: “Evidence indicates that patients with multiple sclerosis experience disease progression during the early stages. This underscores the necessity of early treatment with a preferred therapy such as Kesimpta, which combines robust efficacy with a favorable safety profile and allows for self-administration at home. We are committed to advancing the scientific understanding of the intrinsic disease progression in MS, with the ultimate goal of improving the quality of life for patients living with this chronic condition.”

Kesimpta is a novel targeted B-cell therapy that was approved in the United States in August 2020FDAApproved as a subcutaneous injection for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. In the European Union, Kesimpta was approved in March 2021 for the treatment of adult patients with RMS who have active disease defined by clinical or imaging features.

It is worth noting that Kesimpta is the first and only targeted B-cell therapy that can be easily administered and managed at home, delivered via the Sensoready autoinjector pen as a once-monthly subcutaneous injection, and will become the preferred treatment option for patients with RMS. In Phase 3Clinical TrialCompared with the commonly used first-line drug Aubagio, Kesimpta demonstrated significantly higher efficacy and a similar safety profile, positioning it as the preferred treatment option for a broad population of patients with relapsing multiple sclerosis (RMS).

Traditionally, B-cell binding/depleting agents for the treatment of multiple sclerosis (MS) have been administered primarily in hospitals or infusion centers, which increases healthcare system costs and imposes lifestyle burdens on some patients. Kesimpta is a highly effective B-cell therapy administered via once-monthly subcutaneous injection, enabling patients to self-administer treatment at home and avoid visits to hospitals or infusion centers, thereby addressing a significant unmet need among patients with relapsing forms of multiple sclerosis (RMS).

One of the goals of managing relapsing multiple sclerosis (RMS) is to preserve neurological function and slow the progression of disability. Although several disease-modifying therapies (DMTs) are available for the treatment of RMS, most patients with RMS still experience disease activity. Evidence suggests that initiating high-efficacy therapy early can improve long-term outcomes in patients with RMS.

The regulatory approval of Kesimpta was based on the results of two pivotal Phase III ASCLEPIOS studies. Both studies met their primary endpoints, with data showing that, compared to Aubagio, Kesimpta reduced the annualized relapse rate (ARR) by more than 50% and lowered the relative risk of 3-month confirmed disability progression (CDP) by over 30%. Furthermore, compared to Aubagio, Kesimpta significantly reduced gadolinium-enhancing T1 brain lesions and new or enlarging T2 lesions. The results of these two studies were published in The New England Journal of Medicine on August 6, 2020. An independent post hoc analysis indicated that Kesimpta may halt new disease activity in patients with relapsing multiple sclerosis (RMS), with nearly 90% of patients treated with Kesimpta showing no evidence of disease activity (NEDA-3) during the second year of treatment.

Ofatumumab is a fully human anti-CD20 monoclonal antibody that functions by binding to CD20 molecules on the surface of B cells, thereby inducing effective B-cell lysis and depletion. Ofatumumab was first approved in the United States in 2009FDAApproved and marketed under the brand name Arzerra for the treatment of chronic lymphocyticLeukemia(CLL), this drug requires high-dose intravenous infusion in a healthcare facility.

NovartisSubsequently, ofatumumab for the treatment of RMS was investigated in a new development program, as B cells are well known toAutoimmunityplays a key role in the progression of demyelinating diseases (such as MS). In RMS, the clinical development program for ofatumumab spanned 10 years and, as part of rigorous research, involved more than 2,300 patients worldwide, reflecting a broad patient population. Kesimpta works through a unique mechanism of action, and its treatment regimen (administration) is specifically designed for RMS, playing a critical role in outcomes. This represents a different dosing schedule and route of administration compared to the previously approved indication for CLL.

As a next-generation B-cell depleting agent, Kesimpta offers the advantageous safety profile of rapid B-cell depletion while preserving immunity, along with the convenience of self-administration via once-monthly subcutaneous injection. Since its market launch, it is poised to challenge Roche’s rapidly growing CD20-targeted therapy, Ocrevus (ocrelizumab), whose global sales rose by 24% in 2020 to reach CHF 4.326 billion.

Multiple sclerosis (MS) disrupts the normal functioning of the brain, optic nerves, and spinal cord through inflammation and tissue damage, affecting approximately 2.3 million people worldwide. The disease is typically classified into three types: relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS, generally defined by cognitive and physical changes along with the overall accumulation of disability), and primary progressive multiple sclerosis (PPMS). Approximately 85% of patients initially present with relapsing-remitting multiple sclerosis.

In this field,NovartisThe product portfolio also includes: Gilenya (fingolimod, an S1P modulator), Mayzent (siponimod, a next-generation S1P modulator), and Extavia (interferon beta-1b for subcutaneous injection). In addition, its Sandoz division markets Glatopa (glatiramer acetate, 20 mg/mL and 40 mg/mL) in the United States, which is a generic version of Teva’s blockbuster multiple sclerosis (MS) drug, Copaxone. (Bioon.com)

Original Source: Kesimpta (ofatumumab) data at AAN showed reduction in disability progression independent of relapse activity in newly diagnosed patients with RMS