Therapy Areas: Autoimmune
FDA Approves Genentech's Enspryng for Neuromyelitis Optica Spectrum Disorder
18 August 2020 - - The US Food and Drug Administration has approved Enspryng (satralizumab-mwge) as the first and only subcutaneous treatment for adults living with anti-aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (NMOSD), US-based biotechnology company Genentech said.

Genentech is a member of Switzerland's Roche Group (SIX: RO) (OTCQX: RHHBY).

NMOSD is a rare, lifelong and debilitating autoimmune disorder of the central nervous system, often misdiagnosed as multiple sclerosis, that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis.

Enspryng is a humanised monoclonal antibody and the only approved therapy for NMOSD designed to target and inhibit interleukin-6 receptor activity, believed to play a key role in the inflammation associated with NMOSD.

The treatment was designed using novel recycling antibody technology, which, compared to conventional technology, allows for longer duration of antibody circulation and subcutaneous dosing every four weeks.

Enspryng can be administered in the home by a person living with NMOSD or a caregiver following training from a healthcare provider. Enspryng treatment is administered every four weeks after an initial loading dose.

Enspryng will be available in the United States in two weeks. Genentech is committed to helping patients access the medicines prescribed by their physician.

For people with NMOSD, the Enspryng Access Solutions team is available to answer questions, provide product education, injection training and help families understand insurance coverage and navigate appropriate financial assistance options to start and stay on Enspryng.

FDA approval is based on results from one of the largest pivotal clinical trial programs undertaken for this rare neurological disorder

This approval is supported by results from two randomized controlled Phase III clinical trials, the SAkuraStar and SAkuraSky studies, in which Enspryng demonstrated robust and sustained efficacy and a favorable safety profile in adults with AQP4 antibody positive NMOSD.

Results were sustained for 96 weeks, significantly reducing the risk of relapse compared with placebo as a monotherapy and when used concurrently with baseline immunosuppressant therapy, which has commonly been used to manage NMOSD symptoms associated with relapses.

In the SAkuraStar monotherapy study's AQP4 antibody positive subgroup, 76.5% of Enspryng-treated patients were relapse-free at 96 weeks, compared to 41.1% with placebo.

In the SAkuraSky study, which evaluated Enspryng when used concurrently with baseline IST, 91.1% of Enspryng-treated AQP4 antibody positive subgroup patients were relapse-free at 96 weeks, compared to 56.8% with placebo.

The primary endpoint of both SAkuraStar and SAkuraSky was time to first protocol-defined relapse adjudicated by an independent review committee in the double-blind period.

The most common adverse reactions with Enspryng (incidence ≥ 15%) were nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue and nausea.

SAkuraStar is a Phase III multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Enspryng monotherapy administered to patients with NMOSD.

The primary endpoint is the time to first protocol-defined relapse, adjudicated by an independent review committee in the double-blind period.

Results from the SAkuraStar study were presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 11-13, 2019, and were published in the May 1, 2020 edition of The Lancet Neurology.

Ninety-five adult patients were randomized to either of the following two treatment groups in a 2: 1 ratio: Enspryng (120 mg) or placebo. Both treatments were administered subcutaneously at week 0, 2, and 4. The subsequent treatment was continued at 4-week intervals.

The double-blind treatment period ended at 1.5 years after the enrollment of the last patient. After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with Enspryng in an open label extension period. Patients with aquaporin-4 antibody positive or negative neuromyelitis optica (NMO, as defined by the diagnostic criteria in 2006) and those with AQP4 antibody positive NMOSD were enrolled.

The number of AQP4 antibody negative patients was limited to approximately 33% of the total population of the study. Data have shown that AQP4 antibody positive patients may experience a greater likelihood of relapse and poorer long-term outcomes than AQP4 antibody negative patients.

SAkuraSky is a Phase III multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Enspryng added to baseline immunosuppressant therapy in patients with NMOSD.

The primary endpoint was the time to first PDR as adjudicated by an independent review committee in the double-blind period. Results from the SAkuraSky study were published in the November 28, 2019 edition of the New England Journal of Medicine (NEJM).

Seventy-six adult patients were randomized to either of the following two treatment groups in a 1: 1 ratio: Enspryng (120 mg) or placebo added to baseline therapy (azathioprine, mycophenolate mofetil and/or corticosteroids). Both treatments were administered subcutaneously at week 0, 2, and 4.

The subsequent treatment was continued at 4-week intervals. The double-blind treatment period ended when patients experienced a PDR; the study ended when the total number of PDRs reached 26.

After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with Enspryng in an OLE period.

Patients with AQP4 antibody positive or negative neuromyelitis optica (NMO, as defined by diagnostic criteria in 2006) and those with AQP4 antibody positive NMOSD were enrolled. AQP4 antibody negative patients represented approximately 30% of the SAkuraSky study population.

Enspryng, which was designed by Chugai, a member of the Roche group, is a humanised monoclonal antibody that targets IL-6 receptor activity. The cytokine IL-6 is believed to be a key driver in NMOSD, triggering the inflammation cascade and leading to damage and disability.

Enspryng was designed using novel recycling antibody technology, which compared to conventional technology, allows for longer duration of the antibody and subcutaneous dosing every four weeks.

Positive Phase III results for Enspryng, as both monotherapy and used concurrently with baseline immunosuppressant therapy, suggest that IL-6 inhibition is an effective therapeutic approach for NMOSD. The Phase III clinical development program for Enspryng includes two studies: SAkuraStar and SAkuraSky.

Enspryng is also approved in Canada, Japan and Switzerland. Applications are under review with numerous regulators, including in the European Union and China.

Enspryng has been designated as an orphan drug in the United States, Europe and Japan. In addition, it was granted Breakthrough Therapy Designation for the treatment of NMOSD by the FDA in December 2018.
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