The Food and Drug Administration's advisory panel March 6 meeting on Genzyme Tissue Repair's Carticel cartilage cell culturing service has left everyone a little puzzled.
The panel wasn't asked to advise whether Genzyme should get FDA approval for the Carticel treatment and it didn't. The panel did affirm by a vote of 11-0 that the procedure appeared to provide clinical benefit. However, the panel also found that the data presented by Genzyme in its biologics license application (BLA) was less than that typically seen during the FDA approval process, said Edward N. Hanley, MD, panel chairman.
Most of the information came from an initial study done in Sweden and published in the New England Journal of Medicine. There were additional data from patients in Sweden. The BLA data included some short-term follow-up of patients in the U.S. obtained from a registry established by Genzyme.
"It's not the traditional information that we would normally see from clinical trials," Dr. Hanley said.
The Carticel saga is unusual because originally the FDA said it wouldn't regulate the treatment, then reversed its stance, but gave approval for it to be marketed. On Feb. 28, the FDA issued its new comprehensive regulatory framework for products derived from cells and tissues.
The open hearing came at the request of the FDA's Center for Biologics Evaluation and Research. The FDA did not publish the notice of the hearing in the Federal Register within the usual 15 days prior to the meeting because the notice said, "the agency believes there is some urgency to bring this issue to public discussion and qualified members of the Orthopedic and Rehabilitation Devices Panel were available at this time."
The FDA asked the advisory panel to discuss the criteria that should be included in a study comparing outcomes in patients treated with Carticel and with an external control group. The FDA said, "comparison of the Carticel treatment to an identical treatment (including periosteal flap) except for the cells would yield the best information regarding Carticel. Since there appears to be insufficient experience with such treatment, comparisons to treatments with additional differences could be useful, but will require assessment of the likelihood that observed differences in outcome resulted from the Carticel treatment." The FDA also said it is important to identify a group that is as similar as possible to the Carticel group with respect to factors such as demographics and activity level, size and severity of lesions, underlying disease and nonsurgical management.
The FDA observed that "in the sponsor's functional analysis, based on retrospective questionnaires, approximately 20 percent of the patients reported less function at the time of the questionnaire than before surgery. The absence of a concurrent, randomized control arm makes it difficult to assess whether or not Carticel could have had any negative impact on these patients. While the Carticel data do not suggest any significant systemic toxicities, do these findings raise concerns about deleterious affects?"
Genzyme had planned a post-approval clinical study comparing Carticel to other treatment options to repair damaged knees, but "that is a moot point" until it hears from the FDA about recommended design features of the study, a spokesperson said.