Longer-Term Data Reinforce Safety of Genentech’s NMOSD Therapy

Pooled data from two pivotal phase 3 open-label extension studies show Genentech’s satralizumab was well-tolerated as a monotherapy or in combination with baseline immunosuppressive therapy in people with neuromyelitis optica spectrum disorder, a rare debilitating central nervous system disorder.

Genentech, a Roche subsidiary, will present the new, pooled, pivotal satralizumab safety results at the 6th Annual Meeting of the European Academy of Neurology, which shows satralizumab was well-tolerated in a broad patient population – including adolescents, for whom there is no approved medicine.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, lifelong and debilitating autoimmune disease of the central nervous system that primarily damages the optic nerves and spinal cord, causing blindness, muscle weakness and paralysis. People with NMOSD experience unpredictable, severe relapses directly causing cumulative, permanent, neurological damage and disability. In some cases, relapse can result in death. The disease is most common among non-Caucasian women in their 30s and 40s.

NMOSD is commonly associated with pathogenic antibodies (AQP4-IgG) that target and damage a specific cell type, called astrocytes, resulting in inflammatory lesions of the optic nerves, spinal cord, and brain. AQP4-IgG antibodies are detectable in the blood serum of about two-thirds of NMOSD patients.

Although most cases of NMOSD can be confirmed through a diagnostic test, people living with the condition are still frequently misdiagnosed with multiple sclerosis. This is due to overlapping characteristics of the two disorders, including a higher prevalence in women, similar symptoms, and the fact that both are relapse-based conditions.

Satralizumab is an experimental humanized monoclonal antibody that targets the interleukin-6 (IL-6) receptor, believed to play a key role in the inflammation that occurs in people with NMOSD. Satralizumab was designed using novel antibody recycling technology, allowing for longer duration of antibody circulation and subcutaneous dosing every four weeks.

Positive phase 3 results for satralizumab, as both monotherapy and in combination with baseline immunosuppressant therapy, suggest that IL-6 inhibition may be an effective therapeutic approach for NMOSD. The phase 3 clinical development program for satralizumab includes two studies: SAkuraStar and SAkuraSky.

“The open-label extension data from the Phase 3 studies reinforce the safety, observed tolerability and potential of satralizumab as a future treatment option for this chronic condition,” said Jerome de Seze, department head of Neurology and the Clinical Investigation Centre at the University of Strasbourg, France. “Although significant strides have been made recently in understanding NMOSD, more approved treatment options offering a well-tolerated safety profile with a less frequent, subcutaneous dosing are needed for this underserved population.”

Pooled data from the double-blind periods of the SAkuraStar and SAkuraSky phase 3 studies showed that the rates of adverse events (AE) and serious adverse events (SAEs) were comparable between satralizumab and placebo groups, as a monotherapy or in combination with baseline therapy. The most common AEs in both treatment groups were urinary tract infection and upper respiratory tract infection. No deaths or anaphylactic reactions were reported.

The safety profile of satralizumab in the open-label extension was consistent with the double-blind period with respect to the nature and rate of AEs. There were no meaningful changes in incidence, rate, or type of infections.

In a separate analysis from the SAkuraSky study, adolescents treated with satralizumab (n=8) with the same dosing and frequency demonstrated a benefit-risk profile generally consistent with the adult population.

Finally, based on pharmacokinetic and pharmacodynamics analyses from the phase 1 and the two pivotal phase 3 studies, the dosing regimen of satralizumab, 120 mg every four weeks, showed significant sustained IL-6 signaling inhibition. In the NMOSD population, the pharmacokinetics of satralizumab indicated that the 120 mg dose allowed for more than 95 percent binding to the IL-6 receptor throughout the full four-week dosage period.

Photo: Jerome de Seze, department head of Neurology and the Clinical Investigation Centre at the University of Strasbourg, France

Author: Rare Daily Staff