Ra Pharmaceuticals Announces Positive Top-line Data from Phase 2 Trial of Zilucoplan in Patients with Generalized Myasthenia Gravis
Primary and key secondary endpoints met in a broad spectrum of patients with gMG
Clinically meaningful and statistically significant reductions in both QMG and MG-ADL
Company to host conference call today,
“The rapid, profound, and sustained reductions in QMG and MG-ADL
observed in this Phase 2 study confirm that complement inhibition was
effective across a wide spectrum of MG patients in this study, whether
refractory or non-refractory,” said
“This represents a potential breakthrough for all patients who are
struggling every day with their MG, and seeking more effective and
convenient treatment options,” said
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 gMG, regardless of prior
therapies, who had a MGFA Disease Class of II-IVa at screening and a 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
- The pre-specified primary efficacy endpoint of change from baseline to Week 12 in 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-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).
- QMG and MG-ADL outcomes for the 0.1 mg/kg SC daily dose were similar to but less pronounced than the 0.3 mg/kg SC daily dose, also achieving pre-specified statistical significance on both endpoints.
- The threshold for statistical significance used in pivotal Phase 3 studies (2-sided p<0.05) was achieved in a pre-specified analysis of the pooled active arms versus placebo, which showed a placebo-corrected change in MG-ADL at Week 12 = -2.2 (2-sided p=0.047).
- 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 patients (0%) 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.
Based on these data, Ra Pharma plans to engage with regulatory agencies,
“Since the founding of this Company, our goal has always been to expand
patient access to important therapies,” said
Ra Pharma plans to present the full data from the trial and additional data from the open-label, long-term extension in association with an upcoming major medical meeting.
Conference Call and Webcast
|Date: Monday, December 10, 2018|
|Time: 8:00 a.m. ET|
|Telephone Access:||Domestic callers, dial (844) 419-1655|
|International callers, dial (216) 562-0467|
|Confirmation code: 5059859|
Webcast Access: Go to the Investor Relations section of the Ra Pharma website and follow instructions for accessing the live webcast. Please connect to the website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary.
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 (formerly RA101495 SC)
Ra Pharma is developing zilucoplan for generalized myasthenia gravis (gMG), paroxysmal nocturnal hemoglobinuria (PNH), and other complement-mediated disorders. The product candidate is designed for convenient, once-daily subcutaneous self-administration. Zilucoplan is a synthetic, macrocyclic peptide discovered using Ra Pharma's powerful proprietary drug discovery technology. The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways. By binding to a region of C5 corresponding to C5b, zilucoplan is additionally designed to disrupt the interaction between C5b and C6 and prevent assembly of the membrane attack complex. This activity may define an additional, novel mechanism for the inhibition of C5 function.
Ra Pharmaceuticals is a clinical stage biopharmaceutical company focusing on the development of next-generation therapeutics for complement-mediated 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 potential to
transform treatment paradigms across multiple complement-mediated
disorders, the potential safety, efficacy and regulatory and clinical
progress of our product candidates, including without limitation
zilucoplan, plans to engage with regulatory agencies, beliefs regarding
clinical trial data, and plans for the presentation of clinical data.
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;
the risk that top-line results as of
Natalie Wildenradt, 212-600-1902
David Rosen, 212-600-1902