MACI, New Agent to Repair Damaged Cartilage, Approved by FDA
The US Food and Drug Administration has approved the first product that uses tissue engineering to grow cells on scaffolds using healthy cartilage tissue from the patient’s own knee. MACI (autologous cultured chondrocytes on porcine collagen membrane), manufactured by Vericel Corporation, is indicated for the repair of symptomatic, full-thickness cartilage defects of the knee in adult patients, according to a press release from the agency.1
Cartilage defects in the knee can result from straining the knee beyond its normal motion, or can be caused by overuse, muscle weakness, and general wear and tear. “Different cartilage defects require different treatments, so therapy must be tailored to the patient,” said Celia Witten, PhD, MD, deputy director of the FDA’s Center for Biologics Evaluation and Research. “The introduction of MACI provides surgeons with an additional option for treatment.”
MACI is composed of a patient’s own cells that are expanded and placed onto a bio-resorbable porcine-derived collagen membrane that is implanted over the area where the defective or damaged tissue was removed. Each MACI implant consists of a small cellular sheet containing 500,000 to 1,000,000 cells per cm2 (about 0.16 square inches). The amount of MACI used depends on the size of the cartilage defect, and is trimmed by a trained surgeon to ensure that the damaged area is completely covered. Multiple implants may be used if there is more than 1 defect.
The FDA based their approval on a 2-year clinical trial designed to demonstrate reduced pain and improved function in comparison to microfracture, an alternative surgical procedure for cartilage repair.2 The trial included 144 patients (72 in each treatment group). A majority of the patients who completed the 2-year clinical trial also participated in a 3 year follow-up study. At Week 104, Knee injury and Osteoarthritis Outcome Score (KOOS) pain and function had improved from baseline in both treatment groups, but the improvement was statistically significantly (P<0.001) greater in the MACI group compared with the microfracture group.3 In a responder analysis, the proportion of subjects with at least a 10‑point improvement in both KOOS pain and function was greater in the MACI group (63/72 = 87.5%; 95% CI [77.6%, 94.6%]) compared with the microfracture group (49/72 = 68.1%; 95% CI [56.0%, 78.6%]).3
"Overall efficacy data support a long-term clinical benefit from the use of the MACI implant in patients with cartilage defects," noted the agency. The most common side effect reported by people who received MACI were: joint pain, common cold-like symptoms, headache and back pain.
Important Safety Information
According to the manufactuers website,4 there are an number of important safety recommendations:
- MACI is contraindicated in patients with a known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin. MACI is also contraindicated for patients with severe osteoarthritis of the knee, inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders. MACI is also not indicated for use in patients who have undergone prior knee surgery in the past six months, excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant.
- MACI is contraindicated in patients who are unable to follow a physician-prescribed post-surgical rehabilitation program.
- The safety of MACI in patients with malignancy in the area of cartilage biopsy or implant is unknown. Expansion of present malignant or dysplastic cells during the culturing process or implantation is possible.
- Patients undergoing procedures associated with MACI are not routinely tested for transmissible infectious diseases. A cartilage biopsy and MACI implant may carry the risk of transmitting infectious diseases to healthcare providers handling the tissue. Universal precautions should be employed when handling the biopsy samples and the MACI product.
- Final sterility test results are not available at the time of shipping. In the case of positive sterility results, health care provider(s) will be contacted.
- To create a favorable environment for healing, concomitant pathologies that include meniscal pathology, cruciate ligament instability and joint misalignment, must be addressed prior to or concurrent with the implantation of MACI.
- Local treatment guidelines regarding the use of thromboprophylaxis and antibiotic prophylaxis around orthopaedic surgery should be followed. Use in patients with local inflammations or active infections in the bone, joint, and surrounding soft tissue should be temporarily deferred until documented recovery.
- The MACI implant is not recommended during pregnancy. For implantations post-pregnancy, the safety of breast feeding to infant has not been determined.
- Use of MACI in pediatric patients or patients over 55 years of age has not been assessed.
- The most frequently occurring adverse reactions reported for MACI (≥5%) were arthralgia, tendonitis, back pain, joint swelling, and joint effusion.
- Serious adverse reactions reported for MACI were arthralgia, cartilage injury, meniscus injury, treatment failure, and osteoarthritis.