Roche’s IL-6R Monoclonal Antibody Enspryng (Satralizumab) Significantly Reduces Relapse Severity and Risk in Neuromyelitis Optica Spectrum Disorder (NMOSD)

September 11, 2020 /Bio ValleyBIOON/ -- Roche recently at the 8th ACTRIMS-ECTRIMS JointMeetingLatest data on the anti-inflammatory drug Enspryng (satralizumab) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) were presented at MSVirtual2020. The results demonstrated that Enspryng significantly reduced the severity and risk of relapse in NMOSD, as well as the severity of relapses during the double-blind phase of the Phase 3 SAkura studies (SAkuraStar and SAkuraSky). Furthermore, pooled data from the SAkura open-label extension (OLE) study supported the sustained efficacy of long-term Enspryng use in reducing relapse risk. The data continued to show a favorable safety profile for Enspryng.

NMOSD is a rare, lifelong, debilitating central nervous systemAutoimmunityneuromyelitis optica spectrum disorder (NMOSD), which is often misdiagnosed as multiple sclerosis (MS). NMOSD primarily damages the optic nerves and spinal cord, leading to blindness, muscle weakness, and paralysis. Enspryng is a humanized monoclonal antibody that selectively binds to the interleukin-6 receptor (IL-6R), which is believed to play a key role in the inflammation observed in patients with NMOSD. In August this year, Enspryng received U.S.FDAApproved for the treatment of adult patients with AQP4 antibody-positive NMOSD.

It is worth mentioning that,Enspryng is the first and onlyFDASubcutaneous Regimen Approved for the Treatment of AQP4 Antibody-Positive NMOSD, which can be self-administered by the patient or administered by a caregiver via subcutaneous injection once every 4 weeks. Meanwhile,Enspryng is the first and only treatment that targets and inhibits interleukin-6 receptor (IL-6R) activity for the treatment of NMOSD.In two pivotal Phase III studies (SakuraStar, SAkuraSky), Enspryng demonstrated robust efficacy as both monotherapy and as an add-on to baseline immunosuppressive therapy (IST) in a broad population of patients with neuromyelitis optica spectrum disorder (NMOSD), significantly reducing the risk of relapse.

Research Chair of the Multiple Sclerosis Society of Canada, Neurologist and Professor at the University of British ColumbiaAnthony Traboulsee stated, “The Enspryng data presented at MSVirtual2020 are promising, demonstrating a significant reduction in the severity and frequency of relapses, which is a key treatment goal for patients with NMOSD. Enspryng is the first NMOSD therapy approved for home administration, offering favorable efficacy and safety profiles that are crucial for improving long-term outcomes.”

Data presented at MSVirtual2020 showed that in a post hoc analysis of the Enspryng treatment group during the double-blind phase of the SAkura study, Enspryng reduced the risk of severe relapse by 79% compared with placebo (5 out of 27 patients [19%] vs. 12 out of 34 patients [35%]). Preventing relapses is the primary goal of NMOSD disease management, as the most severe relapses can lead to cumulative, irreversible neurological damage and disability. Compared with the placebo group, patients in the Enspryng treatment group were less likely to require rescue therapy due to relapse (OR=0.46; 95% CI: 0.25–0.86; p=0.015). A relapse was classified as severe if it resulted in an increase of ≥2 points on the Expanded Disability Status Scale (EDSS).

In a separate pooled analysis, Enspryng reduced the risk of relapse by 51% (HR=0.49; 95% CI: 0.31-0.79; p=0.002) during the combined double-blind period and open-label extension (OLE), compared with patients initially assigned to the placebo group. This effect was more pronounced in aquaporin-4 antibody (AQP4-IgG) seropositive patients, who typically experience a more severe disease course, with a 66% reduction in relapse risk compared to the placebo group (HR=0.34; 95% CI: 0.19-0.62; p<0.001).

During the double-blind period, the infection rate was lower in the Enspryng treatment group compared with the placebo group in the SAkuraStar study (99.8 vs 162.6 events per 100 patient-years [PY]), whereas no difference in infection rates was observed between groups in the SAkuraSky study. In each study, the rates of serious infections were comparable between the two groups (SAkuraSky study: 2.6 vs 5.0 events per 100 PY; SAkuraStar study: 5.2 vs 9.9 events per 100 PY). Across the combined double-blind and open-label extension (OLE) periods, the infection and serious infection rates in patients treated with Enspryng were consistent with those observed during the double-blind phase in terms of the nature and incidence of adverse events, and did not increase over time.

Levi Garraway, M.D., Ph.D., Chief Medical Officer and Global Head of Product Development at Roche, stated: “Long-term data for Enspryng further reinforce the efficacy previously observed in this debilitating disease, which is often misdiagnosed as multiple sclerosis (MS). Enspryng is the first and onlyFDAThe approved subcutaneous self-administered therapy for NMOSD, and the first NMOSD drug targeting the interleukin-6 receptor (IL-6R), which is believed to play a key role in the inflammation associated with this disease.”

NMOSD (Image source: empr.com)

NMOSD is typically associated with pathogenic antibodies (anti-AQP4 antibodies) that target and damage a specific type of cell known as astrocytes, leading to inflammatory lesions in the optic nerves, spinal cord, and brain. Anti-AQP4 antibodies can be detected in the serum of approximately 70–80% of NMOSD patients, who tend to experience a more severe disease course. Although most cases of NMOSD can beDiagnosisAlthough diagnostic testing can confirm the diagnosis, up to 30% of patients are still frequently misdiagnosed with multiple sclerosis (MS).

Enspryng is a humanized monoclonal antibody that targets and binds to the interleukin-6 receptor (IL-6R), which is believed to play a key role in inflammation in patients with neuromyelitis optica spectrum disorder (NMOSD). The drug was developed by Chugai Pharma, a member of the Roche Group, using a novel antibody recycling technology. Compared with conventional technologies, this approach extends the duration of antibody circulation, maximally suppresses IL-6 signaling, and minimizes safety risks in chronic disease management. Patients with NMOSD experience unpredictable, severe relapses that directly lead to cumulative, irreversible neurological damage and disability. Preventing relapses through early treatment can have a positive impact on disability prevention, which is the primary goal of NMOSD disease management.

To date, Enspryng has been approved for the treatment of NMOSD in Canada, Japan, Switzerland, and the United States, and is under review by many regulatory authorities, including those in the European Union and China. Satralizumab has been granted Orphan Drug Designation (ODD) in Japan, the United States, and the European Union, and has also been granted Breakthrough Therapy Designation (BTD) in the United States.

Regarding new drugs for NMOSD, in late June 2019, Alexion’s pioneering complement inhibitor Soliris (eculizumab) received U.S.FDAApproved for use in adult patients with AQP4 antibody-positive NMOSD. In late August 2019, Soliris received further approval from the European Union for the treatment of adult patients with AQP4 antibody-positive NMOSD and a relapsing disease course. In both the United States and the European Union, Soliris is the first drug approved for the treatment of NMOSD.

In June this year, Viela Bio's anti-CD19Monoclonal Antibody DrugsUplizna (inebilizumab-cdon, formerly MEDI-551) received U.S.FDAApproved as a twice-yearly maintenance regimen following the initial dose for the treatment of adult patients with AQP4 antibody-positive NMOSD. Notably, Uplizna is the first and only B-cell depleting agent approved for the treatment of adult patients with AQP4 antibody-positive NMOSD.

The active pharmaceutical ingredient of Uplizna, inebilizumab, is a humanized CD19-directed monoclonal antibody that exhibits high affinity for CD19, a protein widely expressed on B cells, including antibody-secreting plasmablasts and some plasma cells. Upon binding to CD19, inebilizumab induces rapid depletion of these cells from the circulatory system.

In late May 2019, Hansoh Pharma entered into a strategic collaboration with Viela Bio to develop inebilizumab for the treatment of NMOSD and other potential inflammatory/Autoimmunityand hematologic malignanciesTumorIndications. Under the terms of the agreement, Viela Bio is eligible to receive an upfront collaboration fee and milestone payments exceeding USD 220 million, as well as tiered royalties based on net product sales. Hansoh Pharmaceutical will be responsible for leading the development and commercialization of inebilizumab in China. (Bioon.com)

Original Source: New data show Roche’s ENSPRYNG (satralizumab) significantly reduces severity and risk of relapse in neuromyelitis optica spectrum disorder (NMOSD)