Only One Clinical Trial Counts with the Charite
BY ROBIN R. YOUNG CFA, JUNE 14, 2004
The FDA panel's recommendation was unanimous. That's the bottom line. Based on a single clinical trial, each member of that panel voted for eventual commercialization of the Charité disc arthroplasty.
And what a clinical trial: 304 patients, randomized, prospective, lead by the Texas Back Institute, presentation by Dr. Scott Blumenthal. It doesn't get much better than that.
At this stage, roughly 8 months before the expected FDA approval, assessing the clinical and economic future of the Charité (and later the ProDisc, the PDN, the Bryant, the Maverick, etc.) is really tantamount to reading tea leaves. Tony, Mark and John Viscogliosi (otherwise known as the V-Bros), who arguably have been the industry's earliest and greatest cheerleaders turned owners/entrepreneurs (Spine Solutions and RayMedica) have pegged the eventual size of the disc arthroplasty industry at over $5 billion.
With first mover advantage, JNJ will start with approx: 95% market share. (Why not 100%? Ongoing clinical trials of other products account for at least 5%.) Build brand loyalty and eventually, own 20-30% market share. It could be a $1 billion revenue business for JNJ, if you believe the V-Bros.
But wait a minute. All is not perfect in Charité land. The public testimony at the FDA panel uncovered a couple of notable concerns and papers at EuroSpine in Porto, Portugal seemed to pile on the negative information. Two surgeons (with financial ties to Medtronic) gave public testimony at the Charité FDA Panel meeting that the Charité's revision surgeries were life threatening. The panel's own data showed that wear debris from the Charité's polymer insert was inflammatory. (Raising the risk of revisions?)
The following are abstracts from both last month's EuroSpine and last year's European Journal of Spine:
Clinical and Radiologic Results after Artificial Disc Replacement - 17 year long follow-up. M Putzier, SV Schneider, AC Disch, H Tautz, JF Funk, Charité Center for Musculoskeletal Surgery, Dept. of Orthopedic Surgery, Berlin, Germany.
Between 1984 and 1989, 71 patients received 84 Charité discs (versions I, II, and III). The report submitted at the Porto conference covered 52 of these patients (with 63 treated segments) and the average follow up period was 17.3 years. The remaining Charité patients were not available for follow up.
The authors of the study report that 23 patients reported excellent or good results based on both subjective measures (Owestry and VAS tests) and objective radiographic evidence of flexion/extension/plain movement. 29 patients, however, reported fair or poor results. 55% of the patients (37 segments) had fused. Interestingly, most of the patients who reported excellent or good results had also been among the group that spontaneously fused.
The authors' conclusions were instructive. In their view, the Charité (or any disc replacement implant) is not indicated for advanced disc degenerative patients, nor for patients with spondylolisthesis.
From Total Disc Replacement for Chronic Low Back Pain: Background and a Systematic Review of the Literature by M. de Kleuver, F. Oner, W. Jacobs in the European Spine Journal Volume 12, Number 2, April 2003.
In this paper the rationale for total disc replacement is discussed, and the authors suggest seven requirements that should be met before the implantation of these devices can be accepted as regular procedures. In an attempt to answer the questions raised, a systematic literature search was performed. The search yielded no controlled trials and nine case series with a total of 564 arthroplasties in 411 patients. The devices used were SB Charité in eight and Acroflex in one study. The percentage results classified as "good" or "excellent" in the studies varied from 50 to 81%. Complications were observed in 3-50% of the patients. Twenty-two of the operated levels were fused either spontaneously or after additional surgery. A meta-analysis to compare the results with other treatments could not be performed due to the lack of comparative studies. Despite the fact that these devices have been implanted for almost 15 years, on the basis of this literature survey there are currently insufficient data to assess the performance of total disc replacement adequately. There is no evidence that disc replacement reliably, reproducibly, and over longer periods of time fulfils the three primary aims of clinical efficacy, continued motion, and few adjacent segment degenerative problems. Total disc replacement seems to be associated with a high rate of re-operations, and the potential problems that may occur with longer follow-up have not been addressed. Therefore, total disc replacements should be considered experimental procedures and should only be used in strict clinical trials.
Like echoes of a distant past, we believe these studies reflect much of the European learning curve experience over the past two decades. Poor patient selection, earlier versions of the prosthesis and complicated instrumentation all contributed to these results.
JNJ is planning to deliver to U.S. surgeons clear guidelines regarding patient selection, will set up comprehensive surgeon training and has re-designed the European instrumentation. And, finally, the Company is basing its launch on a U.S. clinical study that in numbers and sophistication dwarfs anything we have seen so far.
From the FDA perspective, only one clinical study counts. It is the two year clinical trial led by the Texas Back Institute: solid number of patients (304 of which 205 received the Charité), random selection, led by one of the world's leading spine hospitals and a team of surgeons that are generally recognized as among the best in their field, Dr. Scott Blumenthal, Dr. Barton Sachs, Dr. Stephen Hochschuler and their entire team of experienced surgeons, nurses and technicians.
The Texas Back Institute in Plano Texas, like the Mayo Clinic in Rochester, Minnesota, is a combination working hospital and research institute. Combining fundamental research with high volume spine surgeries has made this world-class institution the go-to hospital for both patients and companies with important new innovations.
The two-year clinical trial presented to the FDA Panel by Dr. Blumenthal clearly showed that patients implanted with the Charité Artificial Disc improved more quickly than patients in the control group (BAK cage, fusion). Their pain and functional test scores were statistically superior to those of the fusion patients at many points through 12 months of follow-up and numerically superior at 24 months.
On average, patients treated with the Charité Artificial Disc were discharged from the hospital a half-day sooner than fusion patients. There were no significant differences in complications between the Charité Artificial Disc patient group and the spinal fusion patient group.
Radiographic findings showed an average range of motion of 6.9 and 7.4 degrees for patients with the Charité Artificial Disc at 12 months and 24 months. Disc space height was restored from an average of 5.7 mm pre-operatively to 13.0 mm at 12 months and maintained at an average 12.9 mm at 24 months.
At 24 months, 88% of patients with the Charité Artificial Disc expressed satisfaction with the procedure, compared with 81% of spinal fusion patients. When asked if they would have the same procedure again, 82% of patients with the Charité Artificial Disc said they probably or definitely would, compared to 65% of fusion subjects who answered the same way.
Various versions of the Charité Artificial Disc has been used in, we estimate, over 7,000 patients (principally in Europe) since it was first developed a couple of decades ago. Virtually all the data coming out of Europe regarding the Charité illustrates the long learning curve this device has been on.
In DePuy Spine's submission to the FDA, the Charité Artificial Disc was seeking approval for 'patients with single-level lumbar degenerative disc disease (DDD) from L4 to S1.'
Conclusion: Charité, not only as an implant, but as the first mover will teach the industry in its entirety about disc arthroplasty. Economically, we think disc arthroplasty will be a niche market for the first few years. We noted the recent (8 months ago) comments of one of the Charité's pioneer surgeons, Dr. Theirry David. Dr. David has been using the Charité for 14 years and has performed approximately 350 procedures. He maintains a very narrow indication for the use of discal arthroplasty. How narrow? He estimates it accounts for 4% of his yearly spine surgery activity.
In the United States, we wouldn't be surprised to see some aspects of 'cage rage.' But, we are convinced, with the experienced guidance of JNJ and their advising surgeons it will be kept to a minimum. Furthermore, with improvements and the gathering skill of surgeons, implants like the Charité that preserves segmental motion will become more than mere market niches. Who will be the lead? For about a year, it will be DePuy Spine and their workhorse, Charité.
