Targeted therapy may change the standard of care for patients with generalized myasthenia gravis (gMG).
We believe that understanding the mechanism of disease is a key step in revealing the potential of a targeted peptide therapeutic option. Start with the facts.
Damage to the postsynaptic membrane presents as muscle weakness that can range in severity and may become life-threatening.
The muscle weakness characteristic of the disease may become increasingly severe with repeated muscle use and recover with rest. The weakness may first be confined to specific muscles, such as those responsible for eye movement, but often progresses to affect a broader range, including:
About 20% of patients with gMG suffer a myasthenic crisis, which is defined by the worsening of muscle weakness in the respiratory tract, resulting in respiratory failure. Myasthenic crises may require hospitalization, intubation, and mechanical ventilation.
The current standard of care begins with cholinesterase inhibitors, corticosteroids, immunosuppressants, plasmapheresis, and/or intravenous immune globulin before attempting to use a complement inhibitor.
We believe that patients need a more targeted approach earlier in their disease management. They deserve access to convenient complement inhibition without forgoing any clinical efficacy. Ra Pharma® is researching the capabilities of its small, investigational synthetic peptide therapy that inhibits C5 to control and suppress the terminal complement cascade without the need for intravenous injection.
Ra Pharma has completed a Phase 2 study of the effects of zilucoplan in patients with gMG.
The Phase 2 study consisted of a randomized, double-blind, placebo-controlled multicenter study with an initial 12-week period followed by a long-term extension (LTE) study.
The study enrolled 44 patients.
- Primary Efficiancy Endpoint: Change in QMG score from baseline to week 12.
- Secondary Endpoints Include: Myasyhenia Gravis Activities of Daily Living
Patients enrolled in the trial met the following criteria:
- Diagnosed gMG (Myasthenia Gravis Foundation of America (MGFA) Class II-IVa)
- AChR autoantibody–positive
- Quantitative Myasthenia Gravis (QMG) score of ≥ 12
- Stable doses of corticosteroids and/or immunosuppressants
Notably, patients were not required to have failed multiple prior therapies.
The primary endpoint was defined as the change in QMG from baseline to week 12.
The secondary endpoints are:
In a 12 week, Phase 2 study, zilucoplan demonstrated a rapid, clinically meaningful, and statistically significant reduction in baseline QMG and MG-ADL scores in patients with gMG (n=44).
Pre-specified significance testing at 1-sided alpha of 0.1 with LOCF ANCOVA p values shown; error bars denote standard errors of least squares mean; mITT
- All 44 subjects completed 12-week study; no early withdrawals
- 42/44 subjects (95%) entered long-term extension
- No serious adverse events related to study drug
- No meningococcal infections
- Majority of adverse events mild and not related to study drug