#ECTRIMS2021 – Enspryng Prevents Relapses Over Long Term in Trials
Long-term treatment with Enspryng (satralizumab) safely and sustainably prevents relapses in adolescents and adults with neuromyelitis optica spectrum disorder (NMOSD) who are positive for antibodies against the aquaporin-4 protein (AQP4-IgG), according to four-year data from the SAkura Phase 3 clinical trials.
These benefits were observed when the therapy was combined with standard immunosuppressive treatment or when given alone, supporting its sustained effects in this patient population.
“The positive longer-term efficacy and safety results for Enspryng are important for physicians as they consider Enspryng as a treatment option for their patients,” Ingo Kleiter, MD, of the Ruhr University Bochum, in Germany, said in a press release.
“Just one NMOSD relapse can lead to lifelong disability. An early accurate diagnosis followed by an effective treatment is vital to conserving the quality of life of people with this chronic disease,” added Kleiter, who was also involved in the SAkuraSky trial.
These and other Enspryng findings in NMOSD were shared by Roche through 10 posters at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), being held virtually Oct. 13–15.
Enspryng is an approved antibody-based treatment for NMOSD patients who are positive for anti-AQP4-IgG antibodies — the most common indication of the disease. It works by blocking the activity of interleukin-6, a signaling molecule that drives inflammation in NMOSD.
The therapy was designed based on a recycling antibody technology by Chugai, a subsidiary of Roche, allowing it to stay active in the body for longer and bind repeatedly to its target. It is given through subcutaneous (under-the-skin) injection every four weeks, being the first and only subcutaneous therapy approved for NMOSD.
Its safety and effectiveness in reducing relapse risk in NMOSD patients was demonstrated in the placebo-controlled SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279) Phase 3 trials.
SAkuraSky tested the therapy in combination with standard immunosuppressive treatment in 83 people, 12 and older, with the disease, while SAkuraStar assessed Enspryng alone (monotherapy) in 95 adult patients.
After completing the placebo-controlled period, participants could enter the trials’ ongoing open-label extension portion, in which all would receive the therapy long-term.
Kleiter presented long-term data from the SAkura trials in the poster “Long-term efficacy of satralizumab in aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD): Results from the open-label extension periods of SAkuraSky and SAkuraStar.”
The analysis included 111 NMOSD patients with anti-AQP4 antibodies and who received at least one dose of Enspryng in the placebo-controlled or extension portions of the trials (49 in SAkuraSky and 62 in SAkuraStar).
Patients received the therapy for a median of 4.4 years in SAkuraSky and four years in SAkuraStar.
Efficacy measures included time to first relapse, severe relapse (a relapse combined with at least 2-point disability worsening), and disability worsening sustained for at least 24 weeks (nearly six months). Changes in disability were assessed with the expanded disability status scale (EDSS).
As of Feb. 22, 2021, results showed that Enspryng’s efficacy was maintained over time, with high proportions of patients remaining free from relapses (71%–73%), severe relapses (90%–91%), and sustained disability worsening (86%–90%) after 3.7 years of treatment.
This resulted in a mean annualized rate of relapse of 0.2, with yearly rates ranging from 0.02 to 0.2 in the years one to four.
The effectiveness of Enspryng “is sustained with long-term treatment” and its “favorable safety profile was maintained” up to seven years, “with no new safety findings,” Kleiter said.
Moreover, during SAkuraSky’s extension portion, 16 of the 36 participants (all women) who were initially taking oral steroids were able to reduce their steroid dose from a mean of 10 mg (range of 5–25 mg) to 2.75 mg (range of 0–15 mg).
Seven were initially assigned to a placebo, eight were given Enspryng from the study’s start, and one did not participate in the placebo-controlled portion and entered directly into the study’s extension phase.
These patients received Enspryng for a mean of three years and none was on additional immunosuppressants. Each patient had a unique steroid tapering approach tailored by their physician.
All but two women remained relapse-free after reducing steroid dose, of whom three fully discontinued steroids. Those experiencing clinical relapses showed no changes in the EDSS score and continued treatment.
These findings suggest that steroid dose can be safely reduced while on Enspryng, without increases in relapse rates, but the small number of patients limits strong conclusions, the researchers noted.
These data on steroid tapering were presented by Masami Yamashita, of Chugai, in the poster “Exploring steroid tapering in NMOSD patients treated with satralizumab in the open-label extension period of SAkuraSky: a case series.”
“We are pleased that these longer-term data further reinforce the previously observed efficacy and safety of Enspryng, which was specifically designed for this lifelong, chronic disease by targeting the IL-6 pathway to reduce the frequency of relapses,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, which markets the therapy.
Upcoming SAkuraBONSAI trial
In another poster, titled “SAkuraBONSAI: A prospective, open-label study of satralizumab investigating novel imaging, biomarker, and clinical outcomes in patients with AQP4-IgG seropositive NMOSD,” Jeffrey Bennett, MD, PhD, of the University of Colorado School of Medicine, shared the design of the upcoming Phase 3b SAkuraBONSAI trial.
The international study will evaluate Enspryng’s two-year safety and effectiveness in adults, ages 18–74, with anti-AQP4-IG-positive NMOSD who have either received no previous treatment (60 patients) or failed to respond to rituximab (40 patients).
Rituximab in an immunosuppressive therapy often used off-label in this patient population.
The trial’s main goals are to assess changes in clinical measures related to disease activity and progression, including relapse rates, disability progression, cognitive function, and visual acuity.
The results will provide additional evidence for Enspryng’s use “in NMOSD patient populations where further research is warranted, offering unique insights into potential clinically relevant predictive and prognostic immunologic and imaging markers,” the researchers wrote.
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