Roche's IL-6R Monoclonal Antibody Satralizumab Demonstrates Robust Efficacy in Neuromyelitis Optica Spectrum Disorder (NMOSD)

September 13, 2019/BioValleyBIOON/--The 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)MeetingHeld in Stockholm, Sweden, from September 11 to 13. At this conference, the Swiss pharmaceutical giant Roche announced the complete results of the pivotal Phase III clinical study (SAkuraStar, NCT02073279) evaluating satralizumab (development code: SA237) as monotherapy for the treatment of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab is an investigational humanized antibody against the interleukin-6 receptor (IL-6R), which had previously received U.S.FDAGranted Breakthrough Therapy Designation (BTD) for the treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders (NMO/NMOSD).

SAkuraStar was a multicenter, randomized, double-blind, placebo-controlled study that enrolled 90 male and female patients aged 18–74 years with neuromyelitis optica spectrum disorder (NMOSD) to evaluate the efficacy and safety of satralizumab. The enrolled patients included those with aquaporin-4 antibody-positive neuromyelitis optica (NMO) (according to the 2006 diagnostic criteria) and those with NMOSD (according to the 2007Diagnosiscriteria). In the study, these patients were randomized in a 2:1 ratio to two groups: the satralizumab (120 mg) treatment group and the placebo group. Satralizumab and placebo were administered via subcutaneous injection at weeks 0, 2, and 4, followed by subcutaneous injections every 4 weeks thereafter. The double-blind period ended when either the total number of protocol-defined relapses reached 44 or 1.5 years had elapsed since the enrollment of the last patient, whichever occurred first. Subsequently, patients from both treatment groups entered an open-label extension phase and could continue receiving satralizumab treatment. The primary endpoint was the time to the first protocol-defined relapse during the double-blind period, as adjudicated by an independent review committee. Key secondary endpoints included the Visual Analog Scale (VAS) pain score and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue score.

The results showed that the study met its primary endpoint: in the overall study population, satralizumab monotherapy reduced the risk of relapse by 55% compared with placebo (HR=0.45, 95% CI: 0.23–0.89, p=0.0184). In the larger subgroup (approximately 67%) of AQP4-IgG seropositive patients, the treatment effect of satralizumab was greater, with a significant 74% reduction in relapse risk (HR=0.26, 95% CI: 0.11–0.63, p=0.0014). Patients who are AQP4-IgG seropositive tend to experience a more severe disease course.

In the overall population treated with satralizumab, 76.1% were relapse-free at 48 weeks and 72.1% at 96 weeks, compared with 61.9% and 51.2%, respectively, in the placebo group. Data from the AQP4-IgG seropositive subgroup showed that 82.9% of patients treated with satralizumab were relapse-free at 48 weeks and 76.5% at 96 weeks, compared with 55.4% and 41.1%, respectively, in the placebo group.

These data supplement the results of the Phase III SAkuraSky clinical study, which evaluated satralizumab in combination with baseline therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). The study data were presented at the 34th ECTRIMS Congress in late 2018. The data showed that, when combined with baseline therapy, satralizumab significantly reduced the risk of relapse by 62% compared with placebo in the overall study population, which included representative cohorts of both AQP4-IgG seropositive and AQP4-IgG seronegative patients (HR=0.38, 95% CI: 0.16–0.88; p=0.0184), and by 79% in AQP4-IgG seropositive patients (HR=0.21, 95% CI: 0.06–0.75; p=0.0086).

Overall, the proportion of patients experiencing serious adverse events was similar between the satralizumab monotherapy group and the placebo group in the SAkuraStar study, as well as between the satralizumab plus baseline therapy group and the placebo plus baseline therapy group in the SAkuraSky study. Compared with the placebo group, patients receiving satralizumab had a lower incidence of infections (including serious infections). In both studies, most adverse reactions were mild to moderate in severity, and the most commonAdverse Reactions: In the SAkuraStar study, urinary tract infections and upper respiratory tract infections were reported; in the SAkuraSky study, upper respiratory tract infections, nasopharyngitis (common cold), and headache were reported. Safety analyses continued during the open-label extension phases of the SAkuraStar and SAkuraSky studies.

The above two controlled, randomized Phase III trialsClinical TrialThe data indicate that satralizumab is an effective treatment option, both as monotherapy and in combination with baseline therapy. Satralizumab is administered via subcutaneous injection once every four weeks, which may offer a convenient option for patients and caregivers.

NMOSD is a rare, lifelong, debilitatingAutoimmunitya disease characterized by inflammatory lesions of the optic nerve and spinal cord. Patients with NMOSD often experience a relapsing disease course, with recurrent attacks leading to progressive accumulation of neurological damage and disability. Symptoms include visual impairment, motor dysfunction, and reduced quality of life. In some cases, NMOSD attacks can be fatal. NMOSD is typically associated with pathogenic antibodies (aquaporin-4 [AQP4]-IgG). AQP4-IgG targets and damages a specific cell type known as astrocytes, resulting in inflammatory injury to the optic nerve, spinal cord, and brain. ThroughDiagnosisSex-specific biomarker testing identifies most NMOSD patients as seropositive for AQP4-IgG; however, up to one-third of NMOSD patients are seronegative for AQP4-IgG. This condition is often misdiagnosed as multiple sclerosis.

Satralizumab is a humanized monoclonal antibody that targets the IL-6 receptor to inhibit IL-6 signaling. IL-6 is a cytokine believed to play a key role in the inflammation associated with NMOSD, triggering inflammatory cascades that lead to tissue damage and disability. Patients with NMOSD experience unpredictable, severe relapses that directly result in cumulative, permanent neurological damage.

Jeffrey Bennett, Professor of Neurology and Ophthalmology at the University of Colorado, commented: “The positive Phase III results for satralizumab, first as add-on therapy and now as monotherapy, are highly exciting. Importantly, it has demonstrated efficacy in a broad population of NMOSD patients, reflecting what we observe in daily clinical practice. By targeting the IL-6 receptor, satralizumab may offer a new therapeutic approach. There is an urgent need for controlledClinical Trialapproved treatment regimens that have demonstrated favorable safety and efficacy in China. Because even a single relapse can lead to blindness and motor dysfunction in patients with NMOSD.”(Bioon.com)

Original Source:Roche’s satralizumab significantly reduced relapse risk in second positive phase III study for neuromyelitis optica spectrum