By Lisa Seachrist
GAITHERSBURG, Md. — An FDA advisory panel voted 11-to-0 with one abstention that Genzyme Corp.'s Carticel, a cartilage repair therapy, provides benefit to patients suffering from cartilage damage in the knee.
However, the same panel refused to attribute that benefit to the actual cells that Genzyme's Tissue Repair division produces, maintaining there was not enough data to properly ascertain the role that the implanted cells played.
Carticel is the first tissue-derived therapy to be evaluated under the guidelines to regulate such entities proposed by FDA last week. (See BioWorld Today, March 4, 1997, p. 1.)
"I am very, very pleased by the results of today's meeting," the Cambridge, Mass., company's Chairman and CEO Henri Termeer said. "The panel said that this therapy helps patients, that it is effective."
Termeer said Genzyme planned to seek accelerated approval for Carticel while completing a post-marketing study.
However, Carticel operates as an unregulated service and as such was not required to establish safety and efficacy with controlled clinical trials. As an unapproved product, patients have experienced difficulty obtaining third-party reimbursement.
Under the new framework, the product is classified as a manipulated autologous structural tissue. The new designation will require that Genzyme establish safety and efficacy, however because Carticel uses the patient's own cells (autologous) as the starting tissue for structural repair, the agency agreed not to regulate the product as stringently as it would if the source of the repair tissue came from another person. The agency repeatedly told the advisory committee that they should apply "flexible criteria" in evaluating the merits of Carticel.
Carticel Cartilage Cell Culturing Service is a treatment marketed in the U.S. and Europe to grow a patient's own cartilage cells in culture dishes for implantation into an osteoarthritic knee to repair "holes" in the protective cartilage layer that covers the end of the thigh bone that makes up the knee. Surgeons take a sample of healthy cartilage for the company to expand. In a second surgery, the damaged cartilage is removed from the knee and the new cells are implanted. A small flap of periosteum covers the implant to keep the cells in place.
After the surgery, a patient must stay off of the knee to prevent the implanted cells from dislodging. Physical therapy typically takes six months during which time the cells are producing new cartilage to replace the old.
Genzyme claimed in its presentation to the Orthopedic and Rehabilitation Devices Advisory Committee that the Carticel procedure encourages regrowth of new hyaline cartilage * a smooth, normal, biomechanically strong variety of cartilage. The company claimed this was significant because other procedures (such as joint debridement) while reducing pain in the short term, produce growth of weak fibrocartilage rather than hyaline cartilage.
Genzyme scientists presented data culled from a registry of 217 patients who have been treated with Carticel or autologous chondrocyte implantation therapy in the U.S. as well as 153 patients who had undergone the procedure in Sweden. In the Swedish study, patients who had received the transplant reported 75 percent improvement in function more than a year after treatment.
"These patients had substantial improvement, long-term improvement," said Richard Moscicki, senior vice president, clinical, medical and regulatory affairs at Genzyme. " It is important to remember that the patients had failed other therapies by the time that they received chondrocyte implantation."
The FDA, however, had concerns about the fact that autologous chondrocyte implantation had not undergone the rigors of a randomized clinical trial and that there was very little long-term data on the procedure. For those reasons and to establish the types of clinical trials that may be necessary, the agency brought Carticel before the advisory panel.
In addition, panel member Anthony Poole, director of the Joint Diseases Laboratory, at the Shriners Hospital for Crippled Children, in Montreal, presented data indicating that production of hyaline cartilage in the patients did not clearly correlate with better outcome.
"The problem is that we don't have enough data to clearly say how Carticel is achieving an effect," Poole said. "The cartilage data is not definitive, but it is very encouraging."
When it came down to a vote of whether or not Carticel had a clinical effect, panel member Leela Rangaswamy, deputy editor of the Journal of Bone and Joint Surgery summed up, "It helped the patients."
However, abstaining member M. Clinton Miller chairmen of biometry at the Medical University of South Carolina said, "I abstain because this is a clinical decision not a scientific one."
The panel recommended that the company undertake a randomized post-marketing study to determine what role if any the cells play in relieving the symptoms of cartilage damage.
"We are committed to conducting a post-marketing study," Termeer said. "However, it must be one that we can accomplish."
Trading was halted for Genzyme Tissue Repair's stock (NASDAQ:GENZL) on Thursday. *