Anika Therapeutics announced mixed results from its pivotal Phase III FastTRACK study of Hyalofast, a hyaluronic acid scaffold for cartilage repair, with the treatment failing to achieve statistical significance on its co-primary endpoints while demonstrating improvements in several secondary measures.
The evaluator-blinded, multicenter study compared Hyalofast combined with autologous bone marrow aspirate concentrate (BMAC) against microfracture in patients with articular knee cartilage defect lesions. While Hyalofast consistently demonstrated improvements across all measures of pain and function relative to microfracture, it did not meet the pre-specified co-primary endpoints of percent change from baseline to two years in both Knee injury and Osteoarthritis Outcomes Score (KOOS) pain and International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score.
Study Challenges and Secondary Outcomes
The study, which began in 2015 and completed enrollment in 2023, was impacted by a higher subject dropout rate in the microfracture arm and missed visits during COVID-19. This resulted in missing data that reduced the evaluable sample size and complicated the statistical analysis.
Despite missing the primary endpoints, Hyalofast showed statistically significant improvements in key pre-defined secondary endpoints including KOOS Sports and Recreation Function and Quality of Life. The treatment also demonstrated statistically significant improvement in Total KOOS, a composite pain and function measure. These additional measures have supported prior FDA approvals for cartilage repair products.
"While we are disappointed that the co-primary endpoints were not achieved under the original statistical framework, we are encouraged by the consistency and robustness of our results on pain and function measures including achieving significance on measures used for prior FDA cartilage repair approvals," said Cheryl Blanchard, President and CEO of Anika Therapeutics.
Global Experience and Regulatory Path Forward
Hyalofast has been used to successfully treat more than 35,000 patients since its launch in 2009 and is currently available in more than 35 countries outside the U.S. The treatment has demonstrated a favorable safety and effectiveness profile from real-world clinical experience across multiple independent studies performed outside the U.S., including positive 15-year outcomes published last year.
The treatment exhibited a comparable safety profile when compared to microfracture following the initial effects of the differences in surgical procedure, supporting a favorable benefit-risk profile for Hyalofast.
FDA Submission Plans
Based on the totality of clinical data collected on Hyalofast, Anika plans to file the third and final PMA module in the second half of 2025. The submission will include ongoing additional post-hoc analyses and consideration of additional endpoints previously accepted by the FDA for cartilage repair product approvals.
Anika expects that the FDA will consider these additional post-hoc analyses and the additional data from outside the U.S. as part of its review of the PMA submission under its Breakthrough Device Designation. However, whether these analyses are sufficient to support approval will be a review issue for the FDA.
Hyalofast is a single-stage, off-the-shelf, resorbable hyaluronic acid scaffold that supports the regeneration of hyaline-like cartilage. The FDA has designated it as a breakthrough device, allowing prioritized interaction and review.
