Aer Therapeutics has announced the dosing of the first patient in its Phase 2a proof-of-concept clinical study, AER-01-002, evaluating fexlamose for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The trial is designed to assess the safety and efficacy of fexlamose in patients with high levels of mucus plugs in their lungs.
The Phase 2a study is a randomized, double-blind, placebo-controlled, parallel-group trial. It will administer fexlamose once daily for 28 days to patients with COPD. Aer Therapeutics is employing a novel approach by using computed tomography (CT) lung scans to identify and enroll 100 patients with moderate to severe COPD who exhibit high mucus plug scores, as determined by a scoring system developed at the University of California, San Francisco. This precision imaging strategy aims to enrich the trial population with patients most likely to benefit from fexlamose.
Trial Objectives and Endpoints
AER-01-002 is designed to determine if a 28-day course of once-daily fexlamose, administered via nebulizer, improves lung function. The primary outcome measures include forced expiratory volume in one second (FEV1) and patient-reported outcomes (PROs) assessed by the St. George's Respiratory Questionnaire (SGRQ-C). Secondary endpoints include CT mucus plug score and other functional, imaging, and PRO endpoints. Both FEV1 and SGRQ-C are accepted by regulatory agencies like the FDA and EMA for COPD approval.
Fexlamose: A Novel Mucolytic Agent
Fexlamose is under development as a chronic treatment for COPD and asthma, intended for use alongside standard therapies to improve lung function, reduce symptoms, and enhance quality of life. It may also be explored for treating other muco-obstructive lung diseases, such as cystic fibrosis and non-CF bronchiectasis.
Previous Phase 1 studies in 96 healthy volunteers demonstrated a strong safety and tolerability profile for fexlamose, with mild to moderate, self-resolving adverse events and no serious adverse events (SAEs). The drug also showed no indication of bronchoconstriction or clinically significant hematology or chemistry abnormalities. Pharmacokinetic data suggest its suitability for once-daily dosing. Fexlamose's taste and smell profile, attributed to its proprietary chemistry and manufacturing process, potentially differentiates it from first-generation thiol-based mucolytics like N-Acetylcysteine.
Mechanism of Action
Fexlamose, a thiol-modified carbohydrate, cleaves mucin disulfide bridges to liquefy mucus plugs. Its carbohydrate scaffold is non-toxic and highly water-soluble, allowing it to penetrate mucus plugs effectively. This mechanism of action makes fexlamose a potent and fast-acting mucolytic suitable for pulmonary delivery via nebulizer or dry powder inhalation.
COPD and Unmet Needs
COPD, encompassing chronic bronchitis and emphysema, is characterized by breathlessness and chronic cough. It is a leading cause of death worldwide. While treatments exist for airway smooth muscle tightening and inflammation in COPD, no approved therapies specifically target mucus plugs. The development of such treatments has been hindered by a lack of biomarkers for airway mucus plug pathology. AER-01-002 aims to address this by using CT mucus plug scoring to enrich the trial with patients more likely to benefit from fexlamose.
Management Perspective
"We are highly encouraged by the rapid start-up of AER-01-002 and enrollment of our first patient in Australia. Our clinical investigators are very excited by the novel approach Aer is taking with fexlamose to potentially improve lung function and symptoms in COPD patients with moderate to severe disease. These patients have a large unmet medical need and targeting mucus plugs represents a rational and differentiated approach to increase their lung function and improve their lung health. We expect to complete AER-01-002 by the end of this year," said Dr. John Fahy, founder and Chief Clinical Consultant for Aer.
