Breakthrough Clinical Results
Anika Therapeutics announced topline results from its U.S. pivotal Phase III FastTRACK clinical trial of Hyalofast, a hyaluronic acid scaffold for cartilage repair. While Hyalofast showed consistent improvements over microfracture in pain and function measures, it did not meet the pre-specified co-primary endpoints due to a higher dropout rate in the microfracture arm and missing data from COVID-related missed visits. Despite this, Anika plans to file the final PMA module by the end of 2025, citing statistically significant improvements in secondary endpoints and positive real-world data from over 35,000 patients treated outside the U.S. since 2009. The company believes the totality of the data supports the clinical value of Hyalofast for patients with knee cartilage lesions.
Key Highlights
- Hyalofast did not meet pre-specified co-primary endpoints in the Phase III FastTRACK trial but showed consistent improvements over microfracture.
- Statistically significant improvements were observed in key secondary endpoints and other measures aligned with prior FDA approvals.
- Anika plans to file the final PMA module in H2 2025, leveraging the totality of clinical data, including real-world evidence from over 35,000 patients treated internationally.
- Hyalofast has received Breakthrough Device Designation from the FDA.
Study Design Parameters
Study Design Parameters and Endpoints in Key Trials for Knee Cartilage Lesions
Study Designs
- Retrospective studies with up to 132 patients
- Preliminary studies with 100 patients
- Systematic reviews analyzing 27 studies with 2,592 knees
- Randomized controlled trials including 12 RCTs with 659 patients
- Registry-based studies using propensity score matching
- Case series (Level of evidence 4)
- Prospective cohort studies
Patient Characteristics
- Age ranges: 14-50 years in some studies, over 40 in others, with mean ages from 32.5 to 58.3 years
- Lesion sizes: typically 2.9-4.45 cm², with some studies reporting ranges from 2.3 to 10.0 cm²
- Lesion types: Unipolar lesions (UL) and Bipolar lesions (BL)
- Lesion locations: medial femoral condyle, lateral femoral condyle, patella, trochlea
- Full-thickness chondral lesions (ICRS grade 3-4 or Outerbridge grade 3-4)
- Some studies specifically included patients with varus deformity (>5°)
Treatment Protocols
- Autologous chondrocyte implantation (ACI) versus microfracture (MF)
- Matrix-assisted autologous chondrocyte transplantation (MACT)
- Bioscaffold solution application combined with microfracture
- NeoCart implant (tissue-engineered cartilage)
- Human umbilical cord blood-derived mesenchymal stem cells with high tibial osteotomy
- Mosaicplasty
- Debridement and loose body removal
Assessment Methods
- MRI for determining size, depth, and location of lesions
- Arthroscopy as the "gold-standard" reference test
- Noyes classification system for grading lesions
- Gross pathology examination (GPE)
- Dynamic stabilometry for proprioceptive deficits
Follow-up Periods
- Short-term: 3 months, 6 months, 1 year
- Mid-term: 2-5 years
- Long-term: 7-20 years (one study reporting mean follow-up of 20±3.7 years)
- Multiple assessment timepoints (e.g., 2, 5, and 10 years)
Endpoints and Outcome Measures
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Clinical scores:
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WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)
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IKDC (International Knee Documentation Committee) scores
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Lysholm scores
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KOOS (Knee Injury and Osteoarthritis Outcome Score) with subscales
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VAS (Visual Analog Scale) for pain
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Tegner Activity Scale and Marx Activity Rating Scale
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Cincinnati Knee Rating System
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Imaging assessments:
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MRI with MOCART scoring
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Radiographic assessment using Kellgren-Lawrence scale
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Second-look arthroscopy with ICRS grading
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Other measures:
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Quality of life (QoL)
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Pain relief scores
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Activities of daily living
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Failure rates at 2-year, 3-year, and 5-year follow-up
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Biomarkers: urinary CTX-II
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Histological and biochemical examinations
Statistical Analysis
- Pairwise Fisher exact tests and two-sample t tests
- Pooled analysis to compare outcomes
- Propensity score matching to eliminate confounders
- Correlation, precision, and accuracy metrics
- Inter- and intra-rater agreements
- Pearson correlation coefficient
- Significance typically set at p<0.05
Incidence and Prevalence
Latest Estimates of Knee Cartilage Lesion Prevalence and Incidence
Recent registry-based studies provide valuable insights into the distribution and characteristics of knee cartilage lesions, though comprehensive global incidence rates and worldwide prevalence percentages are not specifically available in the current literature.
A 2023 registry-based study demonstrated that both bipolar lesions (BL) and unipolar lesions (UL) are common enough to create matched comparison groups of 119 patients each, indicating significant prevalence of these specific lesion types.
The 2017 German cartilage registry (KnorpelRegister DGOU) data from 47 centers analyzing 1071 patients revealed that: - 61.8% of knee cartilage lesions were degenerative in nature - 29.6% were injury-related - 8.7% had unclear genesis - Single defects were observed in 77.6% of cases - The medial femoral condyle and the patella were the most frequently affected areas - In 7.6% of knees, the main defect was associated with a defect on the corresponding joint surface
A 2010 arthroscopic study examining 1199 patients with knee pain found that in 80.6% of cases, preoperative radiography suggested signs of knee osteoarthritis. The most frequently recorded cartilage lesions were within the mean bearing zone of the medial femoral condyle (96.2%) and the medial tibia (57.7%). About a third of patients had cartilage lesions within the mean bearing zone of the lateral condyle and tibia. The study also noted that in 3.8% of knees, intraarticular osteophytes were present.
Research from 2012 examining the Osteoarthritis Initiative database with 126 subjects found that cartilage lesions were more frequent in subjects with right knee pain compared to those without knee pain (p < 0.05). Additionally, elevated cartilage T2 values were associated with findings of pain in the early phase of OA.
Across these studies, the medial femoral condyle and patella consistently emerge as the most commonly affected areas for knee cartilage lesions. There also appears to be a significant association between cartilage lesions and knee pain, particularly in the early phases of osteoarthritis.
While these findings provide valuable insights into the distribution patterns and associated factors of knee cartilage lesions in specific study populations, the available data does not offer specific global incidence rates or worldwide prevalence percentages for knee cartilage lesions.
Clinical Trials of Hyalofast Beyond Knee Cartilage Lesions
Based on a thorough review of available information, there is no specific data on clinical trials investigating Hyalofast for indications other than knee cartilage lesions. While one source from 2021 describes Hyalofast as "a matrix based on hyaluronic acid" used in arthroscopic procedures for cartilage lesions and mentions that "It can be used in a variety of joints," there are no details about formal clinical trials for these alternative applications.
The available information does not specify any intervention models, protocols, or administration techniques being used in clinical trials of Hyalofast for non-knee joint applications or extraarticular tissue regeneration.
The current documented use of Hyalofast appears to be primarily focused on treating cartilage defects, chondral lesions, and osteochondral lesions specifically in the knee joint. Without further clinical trial data, it's not possible to detail other indications or intervention approaches for this hyaluronic acid-based matrix beyond its established knee applications.
For patients or clinicians interested in Hyalofast applications beyond knee cartilage repair, consulting the most recent clinical literature or contacting the manufacturer directly would be advisable to determine if any new trials have been initiated for other joint applications.