MapLight Therapeutics has initiated a Phase 2 clinical trial evaluating ML-007C-MA, an investigational M1/M4 muscarinic agonist, for the treatment of schizophrenia. The announcement marks a significant milestone in the company's efforts to address the substantial unmet medical need in psychiatric care for a disorder affecting over 20 million people worldwide.
Phase 2 ZEPHYR Study Design
The Phase 2 ZEPHYR study is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy, safety, and tolerability of ML-007C-MA in adults with schizophrenia experiencing acute exacerbation or relapse of symptoms. The study will enroll approximately 300 patients throughout the United States and assess both once- and twice-daily dosing regimens.
The primary endpoint focuses on the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to Week 5. This standardized assessment tool measures the full spectrum of schizophrenia symptoms, including positive symptoms like hallucinations and delusions, negative symptoms such as social withdrawal and decreased emotional expression, and cognitive impairment.
"This Phase 2 study is designed to be adequately sized and well controlled to evaluate the efficacy, safety and tolerability profile at the doses selected," said Erin Foff, M.D., Ph.D., Chief Medical Officer of MapLight.
Promising Phase 1 Results Drive Advancement
The Phase 2 trial design builds upon results from an extensive Phase 1 development program that included 270 healthy volunteers. According to MapLight, ML-007C-MA demonstrated a differentiated profile in these early studies, showing favorable safety and tolerability results with flexible dosing options.
Key advantages identified in Phase 1 studies include minimal titration requirements and no need for fasting, while achieving cerebrospinal fluid (CSF) exposures expected to be clinically relevant. These characteristics could potentially improve patient compliance and treatment outcomes compared to existing therapies.
Addressing Critical Unmet Medical Need
Schizophrenia represents one of the most challenging psychiatric disorders to treat effectively. The condition is characterized by a complex array of symptoms including positive symptoms of hallucinations, delusions, and disorganized thinking; negative symptoms of social withdrawal, decreased emotional expression, anhedonia, and apathy; and cognitive impairment. These symptoms significantly impair social and occupational functioning, making schizophrenia a leading cause of disability.
"There is a significant need for new and innovative medicines for the treatment of schizophrenia, a disorder that impacts over 20 million people worldwide," said Christopher Kroeger, M.D., M.B.A., Chief Executive Officer and Founder of MapLight. "We are encouraged by the potential of muscarinic agonists to address the full spectrum of schizophrenia symptoms and remain committed to advancing ML-007C-MA to help meet the urgent needs of these patients."
The disorder affects approximately 3 million people in the United States and is associated with increased risk for premature mortality, highlighting the critical importance of developing more effective treatment options.
Novel Mechanism of Action
ML-007C-MA, also referred to as ML-007C/PAC, represents an innovative approach to schizophrenia treatment. The oral, extended-release formulation is a fixed-dose combination of the investigational M1/M4 muscarinic agonist ML-007 co-formulated with a peripherally acting anticholinergic (PAC).
The drug's potential differentiation stems from optimized pharmacokinetic synchronization of its agonist and antagonist components in the periphery, while maintaining strong activation of both M1 and M4 receptors in the central nervous system. This approach aims to maximize therapeutic benefits while minimizing peripheral side effects commonly associated with muscarinic activation.
The Phase 2 ZEPHYR study is registered on ClinicalTrials.gov under identifier NCT07038876, providing transparency and accessibility for patients and healthcare providers interested in participating or following the trial's progress.
