GENZYME TISSUE REPAIR
Carticel® (cultured autologous chondrocytes for implantation) is marketed in the United States and Europe by Genzyme Tissue Repair. It employs a commercial process to culture a patient's own (autologous) cartilage cells, known as chondrocytes, for use in the repair of clinincally significant, symptomatic defects of the femoral condyle (medial, lateral, or trochlear) caused by acute or repetitive trauma. It is not intended as a treatment for people suffering from arthritis.
The ability of a knee joint to function normally depends on the presence of a smooth gliding surface. This is normally provided by articular cartilage, a thin layer of tough tissue which covers the ends of bones where they meet in the joint. People with damage to this cartilage generally display symptoms which include joint locking, catching, localized pain, and swelling. In addition to pain and restricted mobility, chronic injuries to this cartilage over time may lead to debilitating osteoarthritis which can severely impact a person's normal, daily activities.
Carticel® (autologous cultured chondrocytes) is marketed in the United States and Europe by Genzyme Tissue Repair. It employs a commercial process to grow (culture) a patient's own (autologous) cartilage cells, known as chondrocytes, for use in treating damaged articular cartilage of the knee. Once damaged, articular cartilage does not normally regenerate itself. Unlike most tissues, it has limited ability to heal. Some people with cartilage damage undergo arthroscopic surgery to relieve their symptoms. These procedures include debridement and lavage (smooths the surface of the damaged area) and a number of techniques (microfracture, drilling, abrasion arthroplasty) which create fibrous or scar tissue. While this scar tissue does cover the joint surface, it is less durable and resilient than normal articular (hyaline) cartilage. The benefit from all of these procedures lessens with time, especially if the person's pre-injury activity level is maintained. Patients often see a return of their symptoms and are faced with options of living with pain, undertaking another surgical procedure, or in severe cases, possibly a total joint replacement with an artificial knee prosthesis. Approximately 200,000 total knee replacement operations are performed annually in the U.S. at the cost of about $26,000 per total knee replacement. The artificial joint generally lasts only 10 to 15 years and is considered a poor treatment option for people under the age of 50.
The poor long term clinical results of existing treatment options encouraged researchers at the Hospital for Joint Diseases in New York during the early 1980s to develop the use of autologous chondrocyte implantation (ACI) as a treatment alternative. Further development continued at the University of Goteborg and Sahlgrenska University Hospital, Goteborg, Sweden, in an effort to provide a better therapy for people with cartilage damage. In a seven-year pilot study published in October 1994 in the New England Journal of Medicine, the Swedish researchers reported "good-to-excellent results" in 14 of 16 patients with a cartilage defect on the thigh-bone part of the knee treated at least two years earlier. The researchers said the vast majority of patients treated on the thigh-bone part of the knee had developed hyaline-like cartilage, similar to normal cartilage, where the defects had been. As of March 31, 1998, 2,238 surgeons had been trained in the procedure and a total of 1,271 patients had been treated since Genzyme Tissue Repair began marketing the product in 1995. The procedure cost ranges from $17,000 to $38,000, with an average cost of approximately $26,000 per procedure. Genzyme Tissue Repair charges $10,000 per procedure for the cells.
During the second half of 1996, the company increased its focus on educating insurance companies about Carticel (autologous cultured chondrocytes). As a result of this program, several health maintence and utilization review organizations have established protocols for selecting patients and determining which patients have defects that are appropriate for treatment coverage.
Carticel is indicated for the repair of clinically significant, symptomatic, cartilaginous defects of the femoral condyle (medial, lateral or trochlear) caused by acute or repetitive trauma.
The product is not intended for use in patients who have an infection at any of the operative sites, osteoarthritis or inflammatory diseases. It is also not recommended for use in patients with a known history of an allergy to materials of a bovine origin or with an allergy to gentamycin. Instability of the knee or an abnormal distribution of weight within the joint may also adversely affect the success of the procedure and should be corrected prior to Carticel implantation. Patients who have previously had cancer in the bones, cartilage, fat or muscle of the treated limb should also not be treated with Carticel.
In patient data included in the biologics license application, the following were the most frequently reported adverse events: hypertrophic ("overgrown") tissue at the site of the cartilage repair, adhesions, superficial wound infection, inflammation of membranes within the joint and post-operative bleeding.
Fig.1: Articular cartilage (chondral) defect before removing damaged articular cartilage.
Fig.2: Articular cartilage (surface) defect (circled in red) after removing damaged articular cartilage.
Treatment with Carticel starts when an orthopedic surgeon provides Genzyme Tissue Repair with a small sample of a patients healthy articular cartilage which was removed in an arthroscopic surgical procedure. Technicians at the company's cell processing facility in Cambridge, Mass., use proprietary methods to grow millions of new cartilage cells specifically for that patient.
The cells are then delivered to the hospital, where the surgeon implants them into the defect in an open surgical procedure. During surgery, the physician carefully removes damaged tissue and prepares the defect for introduction of the cultured cells. A small piece of the tissue (periosteum) covering the bone is taken from the patient's lower leg, and sutured over the defect to hold the cells in place. The cultured cells are then implanted under this tissue into the defect where they multiply further and integrate with the surrounding tissue to produce durable new cartilage.
Fig. 3: Articular cartilage (surface) defect after periosteal patch is sewn in place.
In February 1999, results from Genzyme Tissue Repair's Cartilage Repair Registry were reported. This registry tracks and measures outcomes for patients treated with Carticel since its introduction in the U.S. in 1995. Over 583 sites participated in the Registry report. The presented data demonstrated a positive safety profile for Carticel and showed highly statistically significant improvements in patient condition at 24 and 36 months after treatment in all four measures: clinician evaluation of knee condition, patient evaluation of knee condition, clinician reports from knee examinations, and patient reports of symptoms.
The clinicians' evaluations showed that 85% of patients with femoral condyle defects were improved after 36 months, while only 8% had scores that declined. The patients' evaluations suggested that 85 percent of the femoral condyle defects were improved, while only 7% had scores that declined.
Data from the registry are consistent with the experience of Swedish orthopedic surgeons who have been using ACI successfully since 1987. New data presented by these surgeons at the annual orthopedic meeting in February 1997 confirmed the long-term benefits shown in the New England Journal of Medicine article. The surgeons reported on 92 patients treated 2-9 years ago. An overall improvement rate of 88% was reported for all patients treated for lesions of the thigh-bone (femur). More notable, they reported a 96% improvement rate in patients treated for single isolated defects located on the weight bearing areas of the femur, who had otherwise stable knees.
Any potential intraoperative and postoperative complications associated with a knee arthrotomy may occur with autologous chondrocyte implantation as well. While there appear to be no particular adverse events directly related to implantation of autologous chondrocytes, risks from the surgical procedure, including infection and inflammatory response, should be taken into consideration. Possible adverse events associated with this therapy may include wound infection, arthralgia, arthrosis, arthropathy, implant complication and fever.
Carticel is currently marketed as under a Biologics License from the U.S. Food and Drug Administration issued in August, 1997. The FDA cleared Carticel for the "repair of clinically significant symptomatic cartilaginous defects of the femoral condyle (medial, lateral, or trochlear) caused by acute or repetitive trauma".
(Courtesy of Genzyme Tissue Repair)
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