Ra Pharmaceuticals Announces Positive gMG Phase 2 and Open-Label, Long-Term Extension Data at the 2019 AAN Annual Meeting
Open-label, long-term extension data show durability of zilucoplan treatment effect, with sustained improvements observed in primary and secondary endpoints at 24 weeks
“Zilucoplan achieved rapid, clinically meaningful, and statistically
significant reductions in primary and secondary endpoints in this Phase
2 study, with a durable and sustained treatment effect observed at 24
weeks for patients in the long-term extension,” said
Base Study Results
- The 0.3 mg/kg dose of zilucoplan consistently achieved rapid, sustained, and near-complete complement inhibition. The 0.1 mg/kg dose of zilucoplan achieved rapid, sustained, but sub-maximal complement inhibition. Based on the pharmacokinetic, pharmacodynamic, and efficacy results, the 0.3 mg/kg dose of zilucoplan was selected for evaluation in the upcoming pivotal Phase 3 trial.
- As previously reported, the pre-specified primary efficacy endpoint of change from baseline to week 12 in Quantitative Myasthenia Gravis (QMG) score was met with zilucoplan dosed at 0.3 mg/kg SC daily, resulting in a clinically meaningful and statistically significant improvement over placebo (QMG reduction from baseline at week 12 = -6.0; placebo-corrected change in QMG at week 12 = -2.8; p=0.05). The key secondary efficacy endpoint of change from baseline to week 12 in the MG Activities of Daily Living (MG-ADL) score was met with zilucoplan dosed at 0.3 mg/kg SC daily, resulting in a clinically meaningful and statistically significant improvement over placebo (MG-ADL reduction from baseline at week 12 = -3.4; placebo-corrected change in MG-ADL at week 12 = -2.3; p=0.04).
- The 0.3 mg/kg dose of zilucoplan led to rapid, statistically significant, and clinically meaningful reductions in additional pre-specified secondary endpoints, the MG Composite (MG-COMP) and the 15-item MG Quality of Life revised scale (MG-QoL15r), versus placebo at week 12 (MG-COMP reduction from baseline at week 12 = -7.4; placebo-corrected change at week 12 = -4.1; p=0.04); MG-QoL15r reduction from baseline at week 12 = -5.9; placebo-corrected change at week 12 = -3.7; p=0.06).
- Rescue therapy with intravenous immunoglobulin or plasma exchange was required by 3/15 (20%) patients in the placebo arm, 1/15 (7%) patients in the 0.1 mg/kg zilucoplan arm, and in zero (0%) patients in the 0.3 mg/kg zilucoplan arm.
- Treatment with zilucoplan had a favorable safety and tolerability profile in the study, consistent with previously-completed Phase 1 and Phase 2 studies. The majority of adverse events (AEs) reported were mild and were not considered by the investigators to be related to study drug. There were no serious AEs observed related to treatment with zilucoplan.
Open-Label, Long-Term Extension Results
Sustained responses were observed for all four efficacy endpoints
after 24 weeks at the 0.3 mg/kg dose of zilucoplan, with changes from
baseline to week 24 as follows:
- QMG = -8.7, p<0.0001
- MG-ADL = -4.5, p<0.0001
- MG-COMP = -10.2, p<0.0001
- MG-QoL15r = -7.5, p=0.0006
Placebo subjects crossing over to the 0.3 mg/kg dose of zilucoplan
after 12 weeks experienced rapid, clinically meaningful, and
statistically significant improvements for all four efficacy endpoints
from weeks 12 to 24, with changes from week 12 to week 24 as follows:
- QMG = -3.1, p=0.01
- MG-ADL = -3.6, p=0.0004
- MG-COMP = -5.5, p=0.004
- MG-QoL15r = -4.0, p=0.04
Based on feedback provided by the
“These Phase 2 data support the competitive profile of zilucoplan in
gMG, and as a convenient, SC self-administered therapy, we believe
zilucoplan has the potential to bring complement inhibition to the
forefront of treatment in this disease,” said
Details of the presentation are as follows:
Abstract Title: Zilucoplan, a Subcutaneously Self-Administered
Peptide Inhibitor of Complement Component 5 (C5), for the Treatment of
Generalized Myasthenia Gravis: Results of a Phase 2 Randomized,
Double-Blind, Placebo-Controlled Trial and Open-Label Long-Term Extension
Session Title: Emerging Science
The presentation and poster from the 2019 AAN Annual Meeting can be accessed by visiting the “Presentations and Publications” section of the Ra Pharma website: www.rapharma.com.
About Zilucoplan Phase 2 gMG Clinical Trial
The Phase 2, multi-center, randomized, double-blind, placebo-controlled
trial was designed to evaluate the safety, tolerability, and preliminary
efficacy of zilucoplan in patients with generalized myasthenia gravis
(gMG), regardless of prior therapies, who had an MGFA Disease Class of
II-IVa at screening and a Quantitative Myasthenia Gravis (QMG) score, a
physician-administered assessment of MG-related muscle weakness, of ≥ 12
at screening and randomization. The trial enrolled 44 patients in the
Myasthenia gravis (MG) is a chronic, autoimmune, neuromuscular disease characterized by weakness and fatigue of skeletal muscles. Patients with MG present with muscle weakness that becomes increasingly severe with repeated use and recovers with rest. Weakness can be localized to specific muscles, such as those responsible for eye movements, but often progresses to affect a broader range, including head, limb, and respiratory muscles. This progression is often described as the generalized, or severe, form of the disease. gMG is estimated to affect approximately 60,000 people in the U.S. alone.
Ra Pharma is developing zilucoplan for generalized myasthenia gravis (gMG) and other tissue-based, complement-mediated disorders with high unmet medical need. The product candidate is designed for convenient, once-daily, subcutaneous (SC) self-administration. Zilucoplan is an investigational, synthetic, macrocyclic peptide discovered using Ra Pharma's powerful proprietary drug discovery technology. The peptide is designed to bind to complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibit its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways.
Ra Pharmaceuticals is a clinical-stage biopharmaceutical company focused on leading the field of complement biology to bring innovative and accessible therapies to patients with rare diseases. The Company discovers and develops peptides and small molecules to target key components of the complement cascade. For more information, please visit: www.rapharma.com.
This press release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, but not limited to, statements regarding our expectations
surrounding the initiation, enrollment, and design of our planned Phase
3 clinical trial of zilucoplan and timing thereof, our efforts to
develop and expand patient access to treatment options for a wide range
of C5-mediated diseases, and bringing innovative and accessible
therapies to patients with rare diseases. All such forward-looking
statements are based on management’s current expectations of future
events and are subject to a number of risks and uncertainties that could
cause actual results to differ materially and adversely from those set
forth in or implied by such forward-looking statements. These risks and
uncertainties include the risks that Ra Pharma's product candidates,
including zilucoplan, will not successfully be developed or
commercialized in the timeframe we expect or at all; as well as the
other factors discussed in the “Risk Factors” section in Ra Pharma’s
most recently filed Annual Report on Form 10-K, as well as other risks
detailed in Ra Pharma’s subsequent filings with the