Treatment with the experimental therapy, zircopran, alleviated symptoms of generalized myasthenia gravis (gMG) across different subgroups of patients participating in the Phase 3 RAISE clinical trial.
Trial data showed consistent treatment effects regardless of sex, age, disease duration, prior use of a particular treatment, or thymoma status.
The findings were shared in a poster titled “RAISE Subgroup Results: A Randomized Phase 3 Trial of Zircoplan in Generalized Myasthenia Graviswas presented at the American Academy of Neurology (AAN) 2023 Annual Meeting, held virtually April 22-27 in Boston.The research was funded by UCBMorethe company that develops Zircoplan.
Zircoplan resulted in ‘consistent improvement’ in all subgroups after 12 weeks
Zircoplan is designed to bind to an immune protein called C5, which prevents activation of the complement system, a part of the immune system involved in the autoimmune attack that causes MG. It is also the target of the approved gMG therapies Soliris (eculizumab) and Ultomiris (ultomiris).
While these approved treatments are administered by injection into the bloodstream, Zircoplan is administered by subcutaneous injection and, unlike injections, can be administered at home.
of Phase 3 RAISE study (NCT04115293) We enrolled 174 adults with gMG who were positive for antibodies to the acetylcholine receptor (AChR), the most common type of antibody that causes MG. Participants were randomized to self-administer zircopran (0.3 mg/kg) or placebo daily for 12 weeks or approximately 3 months.
The primary results of RAISE were published last year and showed that the treatment was superior to placebo in alleviating MG symptoms and improving quality of life across a group of participants.
As previously reported, treatment with zircopran resulted in clinically meaningful improvements in scores of MG activities of daily living (MG-ADL), a measure of symptom severity. At week 12, compared to the placebo group, the zircoplan-treated patient’s score dropped by 2.09 points from baseline (at the start of the study).
In the AAN poster, researchers performed analyzes of prespecified subgroups of patients. These included subgroups in which patients were classified by sex (male or female), age (<65 years vs. ≥65 years), and disease duration (<5 years vs. ≥5 years). The analysis also compared patients with and without thymoma (tumor of the thymus) who were treated with nonsteroidal immunosuppressants with those who were not.
Compared with placebo, treatment with zircoplan resulted in consistent improvements from baseline in MG-specific endpoints at week 12 in all subgroups.
Across all these subgroups, significant improvements in MG-ADL scores from baseline to week 12 were consistently observed in patients receiving zircoplan. In general, patients taking zircoplan had her MG-ADL score drop by 4 to 5 points from her, while patients taking placebo had a drop of about 3 points or less.
Other standardized assessments of disease severity and MG-specific quality of life, including quantitative MG (QMG), MG Composite, and the MG Quality of Life 15-item modified scale, generally performed similarly to the MG-ADL score. showed a trend.
Subgroup analyzes comparing patients with high versus low MG-ADL or QMG scores at study entry also consistently showed broader improvements with zircoplan than with placebo.
“Compared with placebo, treatment with zircoplan resulted in consistent improvements from baseline in MG-specific endpoints at week 12 in all subgroups,” the researchers wrote.
Patients who completed RAISE had the option to enroll in a study called the open-label extension study. Rays-XT (NCT04225871)All participants in this study received daily subcutaneous injections of Zircoplan.
The researchers combined the data from the interim analysis of this extended study withRAISE-XT: An Interim Analysis of Safety and Efficacy in an Open-label Extension Trial of Zircoplan in Patients with Myasthenia Gravis”
For analysis, RAISE or MG0009 (NCT03315130)a previous Zircoplan phase 2 trial.
No new safety concerns have been reported with long-term administration of zircoplan
Results from the extension trial did not reveal any new safety concerns related to long-term zircoplan treatment. Common side effects observed during treatment included headache, diarrhea, and exacerbation of MG.
Patients who received 12 weeks of zircopran in the previous study remained low in mean MG-ADL and QMG scores after an additional 12 weeks of treatment in the extension study. This reflects an improvement. For a patient who had taken a placebo in previous trials, these scores showed a sharp improvement within a week after he started treatment with zircoplan in RAISE-XT.
After 12 weeks of treatment with zircopran in the extension study, patients who had taken placebo or zircoplan in the previous study experienced similar decreases in MG-ADL and QMG scores from baseline in the original study ≥6 point reduction in MG-. ≥8 points in ADL and QMG scores.
In both groups, 3 out of 4 patients showed clinically meaningful improvement on both scores and were considered responders on these measures by week 12 of RAISE-XT.
“RAISE-XT demonstrated long-term efficacy and well-tolerability of zircopran based on data from 12-week double-blind Phase 2 and 3 trials,” said the researchers. I am writing.
Note: The Myasthenia Gravis News Team provides coverage for the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Visit here for the latest coverage of the conference.
