Allay Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to ATX101 for the treatment of post-surgical pain following total knee arthroplasty (TKA) in adults. This decision is based on clinical data from a Phase 2 exploratory dose-ranging trial. The trial demonstrated ATX101's potential to provide sustained, clinically meaningful pain relief for up to four weeks post-TKA, compared to the standard of care.
Clinical Trial Data Supporting BTD
The Phase 2 trial (n=112) compared ATX101 to bupivacaine, the active comparator. Results indicated that ATX101 led to a decrease in opioid use, fewer opioid-related side effects, and improvements in functional activities and patient satisfaction up to 60 days post-surgery. These findings suggest a significant advancement over current treatment methods, which typically provide only a few days of pain relief and often involve complicated treatment regimens.
ATX101: A Novel Approach to Post-Surgical Pain Management
ATX101 is an investigational configuration of bupivacaine, a validated intracellular sodium ion channel blocker, combined with a biopolymer. This design allows for weeks of pain relief following TKA. The therapy is administered at the end of the surgery and gradually dissolves into water and carbon dioxide. Unlike existing pain management approaches that require specialized training, ATX101's simple procedure aims to replace the complex mix of analgesic products currently used for shorter-term pain management.
The Need for Improved Post-Surgical Pain Relief
Total knee arthroplasty is a common orthopedic procedure, with the United States having one of the highest incidence rates worldwide. An estimated four million adults in the U.S. are living with a total knee replacement, representing 4.2% of the population over 50 years of age. With the number of TKA procedures projected to increase by 143% by 2050, the need for effective post-surgical pain management solutions is growing. Current methods often rely on opioids, which carry risks of side effects and potential for misuse. ATX101 offers a non-opioid alternative that could significantly improve patient outcomes.
Regulatory Pathway and Future Plans
The Breakthrough Therapy Designation will enable Allay Therapeutics to work closely with the FDA to expedite the development and review process for ATX101. This includes intensive guidance, organizational commitment involving senior managers, and eligibility for rolling review and other actions to expedite review. Allay Therapeutics plans to initiate a Phase 2B registrational trial early next year to further assess ATX101's potential impact on patient's pain and recovery following TKA surgeries. The trial will involve leading investigative pain centers in the U.S.
About the Phase IIb Trial
The Phase IIb registration trial included 200 patients who were in the process of undergoing TKA at multiple sites across the United States as part of a three-arm, randomized, and controlled study evaluating treatment with ATX101 1,500 mg versus placebo or a bupivacaine active comparator. The primary endpoint of the study was the area under the curve of pain intensity, while secondary endpoints evaluated reduction in use of opioids, opioid-related AEs, and improvement in physical function. Moving forward, the trial is expected to inform additional functional and health economics endpoints for a global Phase III registration trial.
Expert Commentary
"We’re delighted that the FDA granted Breakthrough Therapy designation for ATX101, which we believe recognizes the clear unmet need for novel non-opioid therapies that may provide extended pain relief to patients in the weeks following TKA surgeries," stated Sharon Hall, SVP of Regulatory Affairs at Allay Therapeutics. "This BTD will allow us to work closely with the FDA to efficiently advance the ATX101 development program through its clinical and regulatory milestones, and eventual NDA filing."
