Medical Device Daily National Editor

Carticel, a product made by Genzyme (Cambridge, Massachusetts), while inarguably novel, is far past the novelty stage, and its novel action lasts.

Carticel, used in a procedure known as autologous chondrocyte implantation (ACI), pretty much had "amazing" written all over it when it was introduced in the mid-1990s as the first cell therapy to be approved by the FDA. And it was the subject of data presentations at the annual meeting of the American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Illinois) in San Francisco earlier this month.

First introduced in March 1995, the product received accelerated approval from the FDA in August 1997 after the agency instituted specific cell therapy guidelines. Genzyme conducted confirmatory post-market clinical studies, and in June of last year, the FDA said the commitment had been satisfied.

Roland DeAngelis Jr., director of global marketing for orthopaedic biologics at Genzyme Biosurgery, told Medical Device Daily that one of the points of emphasis for the company in marketing Carticel is that "it doesn't limit [a patient's] future options."

If the Carticel cell-transplantation treatment doesn't work or at least not as well as the physician and/or patient would desire "all [other] options are available," up to an including total knee replacement.

Used by orthopedic surgeons to treat patients who have "clinically significant" articular cartilage lesions on the thigh bone part of the knee caused by acute or repetitive trauma that have not responded to a prior cartilage repair procedure, Carticel treatment starts when an orthopedic surgeon provides Genzyme with a biopsy of healthy cartilage taken from a patient's knee in an arthroscopic procedure.

Technicians at Genzyme's cell culture laboratory in Cambridge use proprietary methods to grow millions of cells from the biopsy, and the cells then are delivered to the hospital, where the surgeon implants them into the patient's knee defect.

The cost of the treatment ranges from $20,000-$35,000, with more than 14,000 patients in the U.S. having had Carticel implants to date.

Genzyme acknowledges that the independent contributions of the autologous cultured chondrocytes and other components of the therapy to outcome are unknown. However, the long-term efficacy of ACI treatment now has been demonstrated in a study reported at AAOS.

The goal of the multi-center study was to determine if a patient's improvement assessed at an early timepoint, defined as 1 to 5 years, with a mean of 4.6 years, after Carticel implantation, could be sustained over a considerably longer period, defined as six to 10 years, with a mean of 9.2 years.

In the study, 72 patients were enrolled from 35 different centers across the U.S. All enrollees had low functional scores an overall condition score of 3.4 points on the Modified Cincinnati Knee Rating System.

Patients were young, with a mean age of 37 years, and had moderate-to-large lesions a mean lesion size of 4.3 cm on the femoral chondyles. And most patients had undergone at least one previous treatment for their cartilage injury.

At their early follow-up, 75% of all patients had experienced "significant" improvement in their knee function a mean improvement of 4.3 in overall condition. Of those patients, 87% sustained improvement at the later follow-up point.

Allen Anderson, MD, of Tennessee Orthopaedic Alliance (Nashville), a well-known sports medicine orthopedist who presented the data at the meeting in a session titled "Durability of ACI: 10-Year Outcome in Multi-center Observational Study," said, "We knew that autologous chondrocyte implantation worked for select patients, but did it last?"

He told MDD, "We knew the treatment worked, but the question was, 'Does it work long-term?'" In Europe, studies had indicated good results from such treatments for an intermediate term of up to six or seven years, Anderson said, "but no long-term results [had yet been] confirmed in the U.S."

He added that the study data "suggest that the ACI technique not only works, but when it works, the results will last for a long time."

The company said, "This is the first long-term data on cell therapy and it supports Carticel as a long-term treatment."

DeAngelis said the data from the trial on which Anderson reported is "robust."

Genzyme also is in the pre-clinical stages of studying a second-generation Carticel II product, which is less invasive to apply, requiring only minimally invasive or arthroscopic surgery. Carticel II uses a "fleece matrix" into which the harvested chondrocyte cells are planted. This fleece is then placed back into the body, usually via arthroscopy, to begin the healing.

DeAngelis told MDD that this newer technique, known as matrix autologous chondrocyte implantation, or MACI, would lessen some of the barriers to use of the original product, namely the surgical procedure needed to implant and hold the liquid cell matrix.

"MACI is a much more convenient method of delivery," he said. "It's the same cells, but seeded onto a collagen membrane. The surgeon takes this membrane, sticks it on the wound site, and the cells then do what they do."

Genzyme is launching a large, multi-center trial in Europe to support the MACI product, with the first patient expected to be enrolled sometime next month. MACI already is available in Australia, Germany and the UK.

"The data in that trial will be collected in such a way as to be used in other regulatory filings," DeAngelis said. He said the company "doesn't anticipate commercialization in the U.S. for another four to five years."

Genzyme also noted that data were presented at AAOS on Synvisc-One, the single treatment of Synvis (hylan G-F 20) indicated in the European Union for treating pain due to osteoarthritis of the knee.

Jörg Jerosch, MD, PhD, of Johanna-Etienne-Hospital (Neuss, Germany), said patients who received Synvisc through a single-injection regimen achieved a "statistically significant" improvement in pain from osteoarthritis of the knee for up to six months.

A study involving 253 patients at 21 sites across Europe showed improvement in pain from osteoarthritis of the knee observed over 26 weeks compared to patients who received placebo.