Ra Pharmaceuticals Announces Positive gMG Phase 2 and Open-Label, Long-Term Extension Data at the 2019 AAN Annual Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Ra Pharmaceuticals, Inc. (Nasdaq:RARX) today announced the presentation of data from the Company’s Phase 2 clinical trial evaluating zilucoplan for the treatment of generalized myasthenia gravis (gMG), including data from the open-label, long-term extension study, at the 2019 American Academy of Neurology (AAN) Annual Meeting, in Philadelphia, PA, from May 4-10, 2019.

“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 James F. Howard, M.D., Distinguished Professor of Neuromuscular Disease and Chief of the Neuromuscular Disorders Section, Department of Neurology, University of North Carolina School of Medicine. “These data provide continued support for the role of this convenient, subcutaneously (SC) self-administered C5 inhibitor as a potential treatment option for a broad range of patients with gMG.”

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 U.S. Food and Drug Administration (FDA), Ra Pharma plans to initiate a single, 12-week, pivotal, Phase 3, randomized, double-blind, placebo-controlled trial evaluating the efficacy of a once-daily, SC self-administered dose of 0.3 mg/kg of zilucoplan versus placebo. The trial is expected to enroll approximately 130 patients with gMG who are acetylcholine receptor (AChR)-antibody-positive, regardless of their prior therapies. The primary endpoint will be the change in the MG-ADL score from baseline to week 12. Following completion of the Phase 3 clinical trial, patients will have the option to enroll into an open-label, long-term extension study.

“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 Doug Treco, Ph.D., President and Chief Executive Officer of Ra Pharma. “We look forward to initiating our pivotal Phase 3 trial in gMG in the second half of this year, as part of our mission of expanding patient access to convenient and accessible therapies.”

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
Date/Time: Tuesday, May 7, Poster Presentation: 11:45 a.m.-12:45 p.m. E.T., Data Blitz Oral Presentation: 12:06 p.m. E.T.

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 U.S. and Canada. At the outset of the 12-week treatment period, patients were randomized in a 1:1:1 ratio to receive daily, subcutaneous (SC) doses of 0.1 mg/kg of zilucoplan, 0.3 mg/kg of zilucoplan, or matching placebo. The pre-specified primary efficacy endpoint was the change in QMG score from baseline to week 12. The key secondary efficacy endpoint was the change in MG Activities of Daily Living (MG-ADL) score, a patient-reported outcome measure, from baseline to week 12. Significance testing was pre-specified at a 1-sided alpha of 0.1. All 44 patients completed the 12-week study and, of these, 42 (95%) entered a long-term extension to receive active study drug.

About gMG

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.

About Zilucoplan

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.

About Ra Pharmaceuticals

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.

Forward-Looking Statements

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 Securities and Exchange Commission. There can be no assurance that the actual results or developments anticipated by Ra Pharma will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Ra Pharma. All information in this press release is as of the date of the release, and Ra Pharma undertakes no duty to update this information unless required by law.

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