FDA Grants Breakthrough Therapy Designation to Allay’s Therapy for Post-Surgical Pain in Total Knee Arthroplasty

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The FDA has granted Breakthrough Therapy Designation (BTD) to Allay Therapeutics’ ATX101, an investigational product for managing post-surgical pain in adults following total knee arthroplasty (TKA). According to the company, the designation was based on results from a Phase II clinical trial, which found that ATX101 provides sustained pain relief for up to four weeks post-surgery, surpassing the standard of care (bupivacaine) in reducing opioid use, opioid-related adverse effects (AEs), and enhancing patient satisfaction and recovery.¹

“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. Despite decades of development efforts, current treatment methods provide only a few days of pain relief with complicated treatment regimens. ATX101 is designed to provide patients weeks of pain relief enabling an active recovery with less opioids used and less opioid-related side effects and risks,” said Sharon Hall, SVP, regulatory affairs, Allay Therapeutics, in a press release. “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. Our planned Phase IIB registrational trial will start early next year with leading investigative pain centers in the US to fully assess ATX101’s potential impact on patient’s pain and recovery following painful total knee replacement surgeries.”

Allay’s Phase IIb dose-ranging trial, which included 112 participants, was concluded early based on a positive interim analysis. Results found that treatment with ATX101 led to a decrease in opioid use, a reduction in opioid-related AEs, and meaningful improvements in functional activities up to 60 days following surgery.

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.²

According to a study published in Osteoarthritis and Cartilage, the United States has the highest incidence rate of knee arthroplasty worldwide, with 235 procedures per every 100,000 people. The authors of the study also stated that in 2012, there were 700,000 TKA procedures in the United States, which accounted for 9% of inpatient hospital stays where a procedure was performed. By 2050, the amount of TKAs performed is expected to increase by 143%. As a result, the authors anticipate that the projected increase will translate into a projected yearly volume of 1.5 million cases by 2050.³

According to the National Institutes of Health, an estimated four million adults in the United States are currently living with a total knee replacement, representing 4.2% of the population over 50 years of age. Their study indicated that the prevalence was higher among females (4.8%) than among males (3.4%) and increased with age.The lifetime risk of primary total knee replacement from 25 years of age is 7%, while over half of adults in the United States diagnosed with knee osteoarthritis will be expected to undergo a total knee replacement.⁴

References

1. Allay Therapeutics Receives FDA Breakthrough Therapy Designation (BTD) for ATX101 for the Treatment of Post-surgical Pain Following Total Knee Replacement Surgery. Business Wire. December 4, 2024. Accessed December 4, 2024. https://www.businesswire.com/news/home/20241204204921/en

2. Allay Therapeutics Announces FDA Acceptance of Investigational New Drug (IND) Application to Initiate Pivotal Phase 2B Trial of ATX101 for the Treatment of Post-surgical Pain Following Total Knee Replacement Surgery. Allay. June 12, 2024. Accessed December 4, 2024. https://www.allaytx.com/news/

3. Projected increase in total knee arthroplasty in the United States – an alternative projection model. ScienceDirect. Accessed December 4, 2024. https://www.sciencedirect.com/science/article/pii/S1063458417311305#:~:text=The%20United%20States%20has%20the,of%20these%20procedures%20is%20important.

4. Estimating the Burden of Total Knee Replacement in the United States. NIH. Accessed December 4, 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC3748969/#:~:text=Results:,undergo%20a%20total%20knee%20replacement.