FDA Panel Decides Charite Approvable with 5 Conditions
BY ROBIN R. YOUNG CFA, JUNE 2, 2004
Despite being implanted in several thousand patients over the course of the past decade, it was a group of 205 Charité patients that the FDA panel scrutinized today before arriving at its recommendation to approve the Charité for commercial sale in the United States. But the approval did not come before the Charité withstood some shots across the bow from doctors concerned with polyethylene wear (most of whom had ties to Medtronic). The standing room only panel meeting began at 10am EST this morning and finally ended at 5:30 PM.
This, we believe, was a truly historic panel meeting. Hundreds of millions of dollars and a number of orthopedic industry careers are riding on the FDA's approval of disc arthroplasty and its eventual use as an alternative to fusion for patients with degenerative disc disease, spondolythesis, tumors and other destabilizing spinal maladies.
Every manufacturer with an interest was either in attendance or listening on the web. We were in the room as well and the following are our notes from this historic panel meeting:
- INDICATION:
- Spinal arthroplasty in patients with single-level degenerative disc disease (DDD) from L4 to S1
- DEVICE DESCRIPTION:
- Two CoCrMo alloy endplates and a UHMWPE core
- The device delivers a Range of Motion (ROM) 'near physiological segment movement with up to 15 degrees bending in flexion/extension and a similar degree to lateral bending and axial rotation to the natural disc.'
- CLINICAL STUDY:
- Objective:
- Evaluate the safety and efficacy of the Charité for treatment of single level DDD
- Demonstrate non-inferiority compared to the BAK interbody fusion device (BAK)
- Non-inferiority margin of 15%
- Design:
- Randomized, prospective, multi-center study
- First 5 subjects at each site = training (not included in data)
- Specific Indications for Use:
- Single level DDD from L4 to S1
- Less than or equal to 3mm spondylolisthesis at involved level
- Greater than or equal to 6 months conservative treatment
- Primary Endpoint:
- Pain and function (ODI)
- Device failures requiring revision, reoperation or removal
- Major complications
- Neurological status
- Definition of Individual Success
- 25% improvement in ODI at 24 months
- No device failures requiring revision, reoperation, removal
- Absence of major complications
- Maintenance or improvement of neurological status at 24 months
- Definition of Study Success
- CONCLUSIONS:
- Training subjects had more adverse events than study subjects
- Charité patients achieved 64% success rate
- BAK patients achieved 58% success rate
- Non-inferiority margin of 10%
- Number of Charité patients: 205
- Number of BAK patients: 99
- PAIN IMPROVEMENT WITH Charité:
- Charité:
- 75% report significant improvement
- 12% some improvement
- 13% no change or worse
- BAK
- 70% report significant improvement
- 14% report some improvement
- 17% report no change or worse
- ISSUES: A number of issues regarding the Charité were raised by both surgeons during the public comment section and by panel members themselves. Probably the biggest issue was the notion of long term follow up. This device is designed to last the life of the patient, but a number of issues, particularly regarding wear rates for the polyethylene component, created some concerns in the minds of the panel. To wit:
- The Charité Articifical Disc includes two articulating surfaces. Will the polyethlyne component create micro particles which in turn would trigger macrophage activation, inflammation or Osteolysis?
- Initial conclusions: wear testing demonstrated that debris was generated but that the debris was submicron in size.
- Three surgeons (interestingly, with financial ties to Medtronic) presented the following concerns during the public testimony section:
- Transverse cracks in the polyethylene portion of the Charité were apparent.
- In one instance, the device had to be removed after 2.9 years.
- In studies of the Charité, there was some evidence of microscopic polyethylene wear, some pit formation and some measurable damage from stress on the inside rim of the implant.
- Osteolytic wear was a concern to these surgeons; polyethylene wear could trigger inflammatory reactions making revision surgery difficult.
- One recommendation was that the end plate be made larger or the surgeons need to be especially skilled in order to correctly mount the device.
- The kinematics of the device increase forces at the facet joint.
- Revisions of the Charité could have life threatening implications.
- Countering those concerns were the experiences of the investigating surgeons and the clinical trial data:
- Adverse events were rare in the 205 patient trial and when occurred, revisions were successful with no evidence of wear debris.
- Long term results with patients were good.
- Ten year range of motion was good.
- Ten year deformation studies show no gross or catastrophic damage.
- Wear simulation studies showed low particulate debris.
- CONDITIONS: With its recommendation to the FDA, the panel asked that the FDA consider the following conditions before commercialization is allowed:
- Continued access patient group should be minimum two years follow up
- Patients receiving implant should be supplied with ID cards with product information
- Lot number
- Date of procedure
- Hospital
- Provide wear data to 10 million cycles on coupled motion should be flexion/extension with lateral bending
- Training be made available to surgeons
- A series of remaining items will be discussed and resolved between the company and the FDA
In conclusion: The FDA panel, we think, is fully aware of the intense interest surrounding disc arthroplasty and their role in approving the first such product. Their concern is for the patient, not the manufacturer, as it should be. And when spine cages were approved, there was a surge in their use and shortly thereafter, a surge in revisions. This effect, now referred to as 'cage rage', was probably on the panel's mind as it was reviewing the data for the Charité. Hence, we think the critical questions and ultimately the focus on careful monitoring, additional testing and follow up. If at all possible, this panel appeared to be saying: Let's be more deliberate and careful with our roll-out of this new, obviously important technology. Let's avoid another 'cage rage.'
