FDA orthopedic panel gives nod to Medtronic rhBMP-2 AMPLIFY for posterolateral lumbar fusion
Posted on the ORTHOSuperSite July 27, 2010

Panelists discussed using the combination device in women of childbearing age, possibly increased cancer risk and problems with the pivotal study’s design

The Food and Drug Administration’s Orthopaedic and Rehabilitation Devices panel voted on July 27 in favor of having the agency approve Medtronic Sofamor Danek’s premarket approval application — PMA P050036 —for the AMPLIFY recombinant human bone morphogenetic protein-2 Matrix System.

The AMPLIFY device, which combines recombinant human bone morphogenetic protein (rhBMP)-2 with a compression resistant matrix, is indicated for single level posterolateral spine fusion (L2-S1) for the treatment of degenerative disc disease in skeletally mature patients.

Medtronic Vice President Tom McGuinness, who serves as the general manager of the firm’s biologics business, noted in a press release that the panel’s affirmative vote represents an important first step in bringing the product to market.

“We will continue to collaborate closely with the FDA to develop the path forward. The potential approval of AMPLIFY,” he stated.

The sponsor conducted a multicenter randomized controlled trial of the device’s safety and efficacy, enrolling 463 patients who failed at least 6 months of conservative care. Of those included in the study, 239 patients were randomized to receive a fusion with the AMPLIFY device consisting of rhBMP-2 at a 2.0 mg/cc concentration and a compression resistant carrier. The 224 control patients’ fusions were performed with autologous iliac crest bone graft.

All patients received the same metallic supplementary spinal stabilization system.

24 month results

The study’s primary endpoints were radiographic fusion success and improvement in pain and disability according to the Oswestry Disability Index (ODI) at 24 months postoperatively. Some patients were followed through 60 months postoperatively.

At 24 months, in the investigational vs. control groups, fusion success was 95.9% and 89.3%, respectively, and ODI success was 73.1 % vs. 72.7%, respectively. ODI success, a measure of functional improvement, was defined as an increase of at least 15 or more points over baseline scores, which needed to be greater than or equal to 30 preoperatively.

Voting results

The 14-member panel included orthopedic surgeons, statisticians, oncologists, epidemiologists and experts with proteins like BMP, who indicated that the device was safe by nine to four votes, with one abstention, and that it was effective, by 10 to three votes, with one abstention.

However, the vote proved much closer on the third vote when panelists were asked to indicate whether the device’s risk/benefit ratio was acceptable to them based on data that officials from Medtronic Sofamor Danek presented. On that final question, they voted six to five in favor of the risk/benefit ratio with three panelists abstained from voting on that question.

Opinions expressed

Kathleen Propert, ScD, of the University of Pennsylvania in Philadelphia, a regular panel member, voted no on all three questions. “I was somewhat on the fence about the safety issue. I think what finally swayed me was just insufficient data on the possible dose dependence and also some of the issues having to do with pregnant women … I just felt I was not reasonably assured,” she said. “As to the efficacy data, it is not that I don’t think…that this device is efficacious. It is just that I feel that there was just insufficient data here.”

Hollis Potter, MD, a radiologist with the Hospital for Special Surgery in New York, who voted no only on the last question, said, “While they did show an increased rate of radiographic fusion, there are limitations.”

Furthermore, “There was really no data on heterotopic ossification. For a BMP product, I think that is necessary,” Potter said.

During the meeting, orthopedic surgeon John S. Kirkpatrick, MD, of the University of Florida College of Medicine, in Jacksonville, tried more than once to get the sponsor to more clearly define what the term “degenerative disc degeneration” meant in their study and to specify for which lumbar conditions the AMPLIFY system was indicated. But at the end of the day, he remained unsatisfied.

“My ‘no’ to the effectiveness [question] was based upon not knowing who to use it on and not having adequate data to show that it made a difference. The noninferiority to me is kind of a 'no' answer when you are comparing it to something that is highly questioned in the spine world as far as a relative or appropriate indication for fusion,” Kirkpatrick said.

If the AMPLIFY device is approved, panel members recommended that the sponsor provide adequate product labeling and post-market studies to elucidate any possible groups of patients who may be at risk for adverse events, known or unknown, to date.

Perspective

I think the recommendation for approval is a positive step forward. This powerful molecule clearly is efficacious in attaining fusion in the posterior spine with proper dose and carrier. The inhibition of donor site morbidity is a huge advantage. That said, surgeons must be cautious as to the potential dangers and side effects that we are being made aware of on an ongoing basis, as well as the significant cost due to lack of competition in this space.

– Todd J. Albert, MD
Richard H. Rothman Professor and Chair
Department of Orthopaedic Surgery
Professor of Neurosurgery
Thomas Jefferson University and Hospitals
Philadelphia

The ORTHOSuperSite is intended for physician use and all comments will be posted at the discretion of the editors. We reserve the right not to post any comments with unsolicited information about medical devices or other products. At no time will the ORTHOSuperSite be used for medical advice to patients.