Enspryng prevents relapses in NMOSD for up to nearly 9 years
Trial data: Approved therapy found safe, effective over long term
Long-term use of the approved therapy Enspryng (satralizumab) safely and effectively prevented relapses in people with neuromyelitis optica spectrum disorder (NMOSD) who have antibodies against aquaporin-4 (AQP4).
That’s according to up to 8.8 years of pooled data from two placebo-controlled Phase 3 clinical trials — SAkuraStar (NCT02073279) and SAkuraSky (NCT02028884) — and their now-completed open-label extension study, called SAkuraMoon (NCT04660539).
“These results from the rollover SAkuraMoon study demonstrate that the safety and efficacy profile of [Enspryng] treatment [with/without immunosuppressants] observed during the pivotal SAkuraSky and SAkuraStar studies was sustained with long-term treatment,” researchers wrote.
The study, “Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study,” was published in Neuroimmunology & Neuroinflammation.
Enspryng blocks key molecule’s protein receptor
NMOSD is an autoimmune disease most commonly associated with self-reactive antibodies targeting AQP4, a protein primarily found on cells that support the nervous system.
It causes inflammation of the spinal cord and the optic nerve, which relays signals between the eye and the brain. This leads to symptoms such as muscle weakness and vision problems. Inflammatory episodes typically occur periodically and are separated by periods of remission.
Given that relapses can cause irreversible neurological damage and cumulative disability, a primary goal of NMOSD treatment is to prevent relapses, usually with therapies that target the immune system.
Enspryng is an antibody-based therapy that works by blocking the receptor protein of the pro-inflammatory molecule interleukin-6. The treatment’s approvals for NMOSD were based on data from the placebo-controlled parts of the global Phase 3 SAkuraStar and SAkuraSky trials, which involved 178 adolescents and adults with NMOSD.
Results showed Enspryng was significantly superior to a placebo at reducing the risk of relapses and disability worsening, for up to nearly two years, in NMOSD patients with anti-AQP4 antibodies.
Participants who completed the placebo-controlled portions of each trial could move to their respective open-label extension portions, where all received the therapy for a longer period.
After those trials, 119 patients chose to enroll in SAkuraMoon, an open-label extension study designed to evaluate Enspryng’s long-term safety and efficacy for up to three more years. They continued receiving the treatment at a dose of 120 mg, alone or in addition to standard immunosuppressive medications.
Previous pooled data, covering up to 4.6 years of Enspryng treatment across these trials, showed the therapy continued to safely and effectively lower rates of relapse and prevent disability progression.
Therapy tolerated well, with no new safety findings
Now, researchers have analyzed final data from SAkuraMoon. Participants received Enspryng for a median of 6.9 years (range, zero to 10 years) across the parent trials and SAkuraMoon. Nearly half (48%) were on Enspryng for at least seven years, and 16 patients (10%) reached 10 years of Enspryng treatment.
At the first treatment dose, the patients’ mean age was 42.7 years, and most were women (86%) and had anti-AQP4 antibodies (66.9%).
The therapy’s safety profile was analyzed in the 166 participants who received at least one Enspryng dose. Nearly all (97.6%) reported adverse events, mostly mild to moderate in severity, and 26.5% experienced serious adverse events.
The most commonly reported adverse events included the common cold (29%), upper respiratory tract infection (28%), headache (27%), urinary tract infection (25%), joint pain (21%), COVID-19 (19%), and pain in the extremities (16%). Nine patients discontinued the treatment due to adverse events.
The rate of adverse events was 299.4 per 100 person-year (PY), and that of serious events was 8.1/100 PY, which was lower than the rates reported in the parent studies. PY represents the number of adverse events expected to occur in 100 people for a year.
This study provides reliable, consistent, long-term data highlighting the favorable safety and efficacy profile of [Enspryng]Â treatment, as monotherapy or in combination with [immunosuppressants] for patients with [AQP4-related] NMOSD.
The rate of infections and serious infections was similar in the SAkuraMoon trial and parent studies, and did not increase with time.
“Overall, [Enspryng] was well tolerated, as an add-on to background [immunosuppressants] or as [a single therapy], in patients with NMOSD, with no new or unexpected safety findings and no fatalities recorded during the study,” the researchers wrote.
Efficacy analysis was conducted on 111 participants with anti-AQP4 antibodies. The overall adjusted annualized relapse rate (ARR) was 0.07, which is lower than the rates reported in the parent trials (0.12 in SAkuraSky and 0.08 in SAkuraStar). After the third year of treatment, the ARR remained consistently below 0.1.
In the parent trials, 71% to 73% of participants were relapse-free after 3.7 years. After 8.8 years, the estimated proportion of patients who remained free of relapses was 67%, while 89% were free of severe relapses, and 64% did not require rescue therapy for an acute relapse.
Finally, 82% of the patients were estimated to be free from sustained disability worsening, as assessed with the validated Expanded Disability Status Scale score.
“This study provides reliable, consistent, long-term data highlighting the favorable safety and efficacy profile of [Enspryng] treatment, as monotherapy or in combination with [immunosuppressants], for patients with [AQP4-related] NMOSD,” the researchers concluded.
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