Roche’s IL-6R Inhibitor Enspryng Approved in EU and China for AQP4-IgG+ NMOSD

NMOSD (Image source: empr.com)

June 28, 2021 /BioonBIOON/ -- Roche recently announced that the European Commission (EC) has approved 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) to reduce relapses and prevent permanent disability.

Notably, Enspryng is the first and only one in the European UnionAlso suitable for adults and adolescents (≥12 years of age)A drug for the treatment of AQP4-IgG seropositive NMOSD. In addition, Enspryng is the first and only that can`At-home subcutaneous injection therapy`An NMOSD medication that, following appropriate training, is permitted for home administration via subcutaneous injection once every 4 weeks. Enspryng is also the first and onlyTargeted Inhibition of Interleukin-6 Receptor (IL-6R) Activity for the Treatment of NMOSDdrugs.

To date, Enspryng has been approved in 54 countries. NMOSD is a rare, lifelong, debilitating central nervous system`Autoimmunity`...disease, primarily damaging the optic nerves and spinal cord, which can lead to blindness, muscle weakness, and paralysis. Approximately 70–80% of NMOSD patients are positive for AQP4-IgG, and these patients typically experience a more severe disease course.

In two pivotal Phase III studies,Enspryng, as a monotherapy and as an add-on therapy to baseline immunosuppressive therapy (IST), demonstrated robust efficacy, significantly reducing the frequency and severity of relapses in patients with AQP4-IgG-positive NMOSD.

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

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 preventing disability, which is the primary goal of NMOSD disease management.

Enspryng is a humanized monoclonal antibody targeting the interleukin-6 receptor (IL-6R), which is believed to play a key role in inflammation in patients with NMOSD. The drug is developed by Chugai Pharma, a Roche Group company,Developed using novel recycling antibody technology. Compared with conventional technologies, this technology prolongs the antibody's circulation time and enables repeated binding to the target cells (IL-6R), thereby maximally sustaining the inhibition of IL-6 signaling in chronic diseases such as NMOSD, and supports subcutaneous administration once every 4 weeks.

EU Approves Enspryng, Based on the Largest Pivotal Trial Conducted for NMOSDClinical TrialPositive results from one of the studies. Data from two randomized controlled Phase III trials (SakuraStar and SAkuraSky) confirm that, in patients with AQP4 antibody-positive NMOSD, Enspryng demonstrates robust and sustained efficacy and a favorable safety profile as monotherapy and in combination with baseline immunosuppressive therapy (IST, commonly used to manage relapse-associated NMOSD symptoms): 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. Results showed that in the AQP4 antibody-positive subgroup, at Week 48 of treatment, 83% of patients in the Enspryng group were relapse-free compared with 55% in the placebo group; at Week 96, 77% of patients in the Enspryng group were relapse-free compared with 41% in the placebo group.

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

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

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

Regarding new drugs for NMOSD, in late June 2019, Alexion's first-in-class complement inhibitor Soliris (eculizumab) received USFDAApproved for adult patients with anti-AQP4 antibody-positive NMOSD. In late August 2019, Soliris received additional approval in the European Union for adult patients with AQP4 antibody-positive NMOSD with a relapsing disease course. In 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, the transaction has recently cleared US antitrust review.

June 2020, Viela Bio's anti-CD19Monoclonal antibody drugsUplizna (inebilizumab-cdon, formerly known as MEDI-551) received U.S.FDAApproved, following the initial dose, as a twice-yearly maintenance regimen for the treatment of adult patients with anti-AQP4 antibody-positive NMOSD. Notably, Uplizna is the first and only B-cell depleting therapy approved for the treatment of adult patients with AQP4 antibody-positive NMOSD.

Inebilizumab, the active pharmaceutical ingredient of Uplizna, is a humanized CD19-directed monoclonal antibody with high affinity for CD19, a protein widely expressed on B cells, including antibody-secreting plasmablasts and a subset of plasma cells. Upon binding to CD19, inebilizumab induces rapid depletion of these cells from the circulation.

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

Original Source:Roche’s ENSPRYNG approved by European Commission as first and only at-home subcutaneous treatment for neuromyelitis optica spectrum disorder (NMOSD)