Roche’s IL-6R Monoclonal Antibody Enspryng Nears EU Approval for NMOSD, Enters Priority Review in China

April 24, 2021 /BioValleyBIOON/ -- Roche recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Enspryng (satralizumab) as monotherapy or in combination with immunosuppressive therapy (IST) for the treatment of adolescent (aged ≥12 years) and adult patients with aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a rare, lifelong, debilitating central nervous systemAutoimmunityDemyelinating diseases, which primarily damage the optic nerve and spinal cord, can lead to blindness, muscle weakness, and paralysis.. Approximately 70-80% of NMOSD patients are AQP4-IgG positive, and these patients often experience a more severe disease course.

Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which typically makes a final decision within two months. If approved,Enspryng will be the first and only drug in the European Union approved for the treatment of AQP4-IgG seropositive NMOSD in both adults and adolescents (≥12 years of age).Enspryng is the only subcutaneous treatment option for NMOSD, administered once every 4 weeks at home.

To date, Enspryng has been approved in 20 countries, including the United States, Canada, Japan, and Switzerland. Regulatory reviews are ongoing in multiple countries. In China, Enspryng was included in the Priority Review and Approval Program in July 2020. Enspryng has been granted Orphan Drug Designation (ODD) in Japan, the United States, and the European Union, and has also received Breakthrough Therapy Designation (BTD) in the United States.

It is worth mentioning that,Enspryng is the first and only one approved by the U.S.FDAApproved subcutaneous regimen for the treatment of AQP4-IgG seropositive NMOSD, administered via subcutaneous injection every 4 weeks by patients themselves or caregivers.Furthermore, Enspryng is the first and only therapy targeting the inhibition of interleukin-6 receptor (IL-6R) activity for the treatment of NMOSD. In two pivotal Phase III studies, Enspryng demonstrated robust efficacy in a broad population of patients with NMOSD, both as monotherapy and as an add-on to baseline immunosuppressive therapy (IST), significantly reducing the risk of relapse.

NMOSD is typically associated with pathogenic antibodies (anti-AQP4 antibodies) that target and damage a specific type of cell called 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).

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.

Enspryng is a humanized monoclonal antibody that targets 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 diseases.

Dr. Levi Garraway, Chief Medical Officer and Global Head of Product Development at Roche, stated: “Treatment options for patients with neuromyelitis optica spectrum disorder (NMOSD) in the European Union are limited. Today’s positive opinion from the Committee for Medicinal Products for Human Use (CHMP) marks an important step toward providing Enspryng to NMOSD patients in the EU. The drug has been shown to significantly reduce the risk of relapse while demonstrating a favorable safety profile. Furthermore, if approved, Enspryng will be the first and only therapy that can be self-administered via subcutaneous injection at home after appropriate training.”

NMOSD (Image source: empr.com)

CHMP’s positive opinion, based on the largest pivotal study conducted in NMOSDClinical TrialsPositive results from one of the projects. Data from two randomized, controlled Phase III studies (SakuraStar and SAkuraSky) confirmed that in patients with AQP4 antibody-positive NMOSD, Enspryng demonstrated robust and durable efficacy and a favorable safety profile, both as monotherapy and in combination with baseline immunosuppressive therapy (IST, commonly used to manage NMOSD symptoms associated with relapses): compared with placebo, Enspryng significantly reduced the risk of relapse, with efficacy sustained through 96 weeks.

——SAkuraStar Study:Conducted in adult patients with NMOSD, the study evaluated the efficacy and safety of Enspryng monotherapy versus placebo. The results showed that in the AQP4 antibody-positive subgroup, 83% of patients in the Enspryng treatment group were relapse-free at Week 48, compared to 55% in the placebo group; at Week 96, 77% of patients in the Enspryng treatment group were relapse-free, compared to 41% in the placebo group.

—SAkuraSky Study:Conducted in adult and adolescent patients with NMOSD, the study evaluated the efficacy and safety of Enspryng combined with baseline IST versus placebo combined with baseline IST. The results showed that in the AQP4 antibody-positive subgroup, 92% of patients in the Enspryng + IST group remained relapse-free at Week 48 and Week 96, whereas 60% and 53% of patients in the placebo + IST group remained relapse-free at Week 48 and Week 96, respectively.

In the Phase 3 study, Enspryng demonstrated a favorable safety and tolerability profile. The most commonAdverse ReactionsYes: headache, arthralgia, decreased white blood cell count, hyperlipidemia, and injection-related reactions.

The above two controlled, randomized Phase III trialsClinical TrialData indicate that Enspryng is an effective treatment option, whether as monotherapy or in combination with baseline therapy. Administered via subcutaneous injection once every four weeks, Enspryng offers a convenient treatment option for patients and caregivers.

In terms of new drugs for NMOSD, in late June 2019, Alexion's first-in-class complement inhibitor Soliris (eculizumab) received U.S.FDAApproved for adult patients with AQP4 antibody-positive NMOSD. In late August 2019, Soliris received additional approval in the European Union for 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. Notably, in December 2020,AstraZenecaAnnounced the acquisition of Alexion for $39 billion, a deal that has recently cleared U.S. antitrust review.

June 2020, 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 neuromyelitis optica spectrum disorder (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 circulation.

In late May 2019,Hansoh Pharma and Viela Bio Reach Strategic Partnership to Develop Inebilizumab in ChinaTreatment 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 Pharma will be responsible for leading the development and commercialization of inebilizumab in China. (Bioon.com)

Original source: CHMP recommends EUapproval of Roche’s ENSPRYNG (satralizumab) for adults and adolescents with neuromyelitis optica spectrum disorder (NMOSD)