BB&T Executive Editor
BB&T Washington Editor

Med-tech powerhouse Medtronic (Minneapolis) once again demonstrated its power in med-tech last month by opening the door to an entirely new sector in orthopedic technology in the U.S. The company in mid-July won FDA approval for its Prestige artificial cervical disc, and immediately after received an advisory panel recommendation for approval for its Bryan artificial cervical disc.

Uptake of the devices is not one of those “slam-dunk” market coups, however, given the barriers to the broader artificial disc sector: adverse events experienced by some who have been implanted with artificial lumbar discs and the lack of reimbursement.

On July 18, the company reported winning FDA approval of the Prestige made by Medtronic Spinal and Biologics (Memphis, Tennessee), the very first FDA approval of this type of device in the U.S. Immediately after, the agency’s orthopedic and rehabilitation devices advisory panel voted 7-1 to recommend approval of the Bryan cervical disc system made by Medtronic Sofamor Danek (Memphis).

The company banners the primary feature of the Prestige as the ability to improve motion. Constructed of stainless steel in “a unique, two-piece ball-and-trough configuration,” the device “is designed to preserve mobility and alignment at the treated vertebral segment,” according to the company. The alternative for patients suffering degenerative disc disease (DDD) is a surgical procedure, anterior cervical discectomy and fusion, which usually results in limiting motion.

The company won a panel recommendation for approval of the Prestige last September and had projected final approval in the first half of 2007. So the agency’s action was a bit off that mark.

The FDA panel had given its recommendation, with conditions, including the requirement for post-marketing surveillance and the stipulation that the company cannot claim that the Prestige is superior to spinal fusion, a recommendation that the claim be limited to “non-inferiority.”

The panel also recommended that the FDA limit Medtronic’s use of clinical motion discussions in marketing literature and require more analysis of pre-clinical toxicity.

Medtronic was seeking a claim that the Prestige is superior to surgery, but the FDA declined to endorse that claim. The can only say that the device is “as safe and effective” as surgery, thus another limiter of market uptake.

Among the conditions the conditions the company agreed to for final approval is the performance of a seven-year study to evaluate long-term safety and effectiveness and a five-year enhanced surveillance study.

The Prestige was studied in a multi-center, randomized clinical trial to assess safety and effectiveness, based on comparisons between data collected from patients with single-level symptomatic cervical DDD at one level between C3-C7. Application for the device was based on a study of 276 patients received the Prestige Cervical Disc device and 265 patients in a control group receiving an anterior plated surgical fusion utilizing bone graft and plate stabilization.

The company billed the 541-patient study as the largest ever conducted for an artificial disc for the cervical application.

It said that the results showed that the Prestige had superior outcomes in neurological success, as well as overall success, a measurement that includes several safety and effectiveness outcomes, when compared to spinal fusion. The study also showed equivalent Neck Disability Index measures and fewer revision surgeries for patients who received the Prestige Cervical Disc.

J. Kenneth Burkus, MD, an orthopedic surgeon at the Hughston Clinic (Columbus, Georgia), said, “Now patients suffering from cervical degenerative disc disease [DDD] have an alternative to motion limiting spinal fusion.”

At an anticipated price of $4,500 per surgical set for the Prestige vs. that of the surgical set for standard spinal fusion (said to run between $3,000 and $3,500), analysts indicated that Medtronic will have to make a strong argument for its product in order to foster a healthy sales volume. But given its head start in the sedtor, the company is expected to offer a very controlled roll-out of the Prestige — and perhaps the Bryan — before other companies pursuing this opportunity join the race.

The orthopedic and rehabilitative devices advisory panel meeting of the FDA had the job of considering a pair of fairly novel design features of the Bryan artificial cervical disc: the absence of screws to affix the device to the spine, relying instead on a pocket milled into the vertebrae as a source of fixation, abetted by a beaded porous coating on the upper and lower surfaces to provide traction; and the use of polyurethane in the interior of the disc. This latter feature was a point of contention for the one panelist who voted against approval. While the polyurethanes used in the Bryan are generally well characterized, their use in this specific application is without precedent.

Subjects in the control arm received the Atlantis cervical plate, also made by Sofamor Danek, for stabilization of fusion done with “commercially available allograft,” according to FDA documents.

Stephen White, VP of R&D for Sofamor Danek, said that the Bryan’s porous titanium shell is also found in some hip replacement devices. The polyurethane sheath that wraps around the device’s middle was incorporated to facilitate a one-piece insertion into the spinal column and to retain saline lubricant. The Bryan allows 11 degrees of flexion, extension, and left and right bending, and White said that the domed shape of the Bryan “maximizes the stability of this device.” White also said of the polyurethane nucleus that “this and similar materials are currently 510(k)-cleared in two devices.”

FDA indicated that the final bench-top test, used to assess lifetime durability, subjected one of the devices to 40 million cycles, or the equivalent of 295 years of in vivo use. That test resulted only in a “hole in the rim of the nucleus” of the device.

FDA documents indicated that another bench test that examined the wear caused by the interface of the titanium shell and the polyurethane interior from 10 million cycles at 130 newtons. No large pieces of polyurethane broke off, and the test generated less than 15 milligrams of debris, with more than 90% smaller than one micron. Tests in bovine solution yielded “comparable results.”

Ann Ferriter, a mechanical engineer who served as the lead reviewer for the agency on the application, said that this application involved the first use of this combination of materials and employed “a novel method of affixing” the device to the bone.

“We commend the sponsor for enrolling roughly equal numbers of men and women in their trial,” Ferriter said, adding that the overall success rate was more than 80% for the Bryan and about 70% for the controls.

She said that the Bryan had “roughly the same adverse event rate” as the controls.

FDA documents stated that the company performed worst-case testing “at FDA’s request,” but panelist John Kirkpatrick, MD, a professor of orthopedics at the University of Florida College of Medicine (Gainesville), asked why wear testing was restricted to what he described as “the neutral zone.” He said that this is “the area of the stress-strain curved that sees very little stress” in normal daily activities.

A total of 117 patients were enrolled but never received treatment, a source of some concern for the panel. Eight enrollees could not follow through due to insurance issues, and 32 who were randomized to the control arm dropped out of the trial due to “dissatisfaction with the results of randomization.” Eight were lost to failing inclusion/exclusion criteria, and 18 left the study because of improvement in their symptoms without either surgery.

Steve Kurtz, PhD, president of Exponent (Menlo Park, California), an engineering consultancy, said that his firm had looked at retrieved Bryan discs — 15,000 of which implanted outside the U.S. — and said that he saw “no evidence of damage from oxidation” or other forces out to 6.1 years in the polyurethane center of the disc.

Paul Anderson, MD, an associate professor of orthopedic surgery at the University of Wisconsin School of Medicine and Public Health (Madison), told the panel that he had explanted some of the units from animal models and that, even with microscopes and Fourier transformation infrared spectroscopy, the polyurethane components of those discs “are virtually identical to controls,” which were bagged and sealed after manufacture.

However, one of the panelists, Sanjiv Naidu, MD, an orthopedic surgeon with the Penn State Fredericksen Outpatient Center, termed as “bunk” the assertion that there was no degradation in serious quantities. He complained about the lack of data for a friction coefficient between the polyurethane core and the titanium shell, saying that he was “not thrilled with the material data presented to the panel.”

Despite Naidu’s reservations, the other panelists voted to recommend approval of the device with a number of conditions: one that the company would conduct a trial “expeditiously” to examine reports of kidney problems seen in some rodent models;

Another was that the post-approval study will examine kyphosis (spinal curvature) and heterotopic ossification.

Kathryn Simpson, PhD, medical officer of Sofamor Danek, emphasized that the trial demonstrated superiority of the cervical disc compared to surgical fusion, but the panel voted to recommend to the FDA not to allow the firm to make such a claim in its product literature.

Rick Wise, med-tech analyst with Bear Stearns, issued a note saying that approval of both products would produce only “modest immediate financial impact” but longer-term “are key components’ of the Spine division’s growth strategy.”

Winning reimbursement could also be a long road. Nevertheless, Prudential Equity Group has projected that sales for the Prestige could reach $400 million by FY11.

Casting a certain amount of shadow over the artificial disc sector are negatives concerning previous approvals of devices used in the lumbar region, specifically lawsuits claiming adverse events as a result of implants of the Charité, made by Depuy Spine (Raynham, Massachusetts), the orthopedic business of Johnson & Johnson (New Brunswick, New Jersey).