FDA advisory committee votes 6-1 against approval of OP-1 Putty

A Food and Drug Administration advisory committee voted 6-1 Tuesday against recommending the approval of Stryker Corp.’s OP-1 Putty, a product designed to help fuse bones during spinal surgery.

The FDA initially approved OP-1 Putty in April 2004 under the Humanitarian Device Exemption program, and the device currently has approval for use in 4,000 or fewer patients per year. Stryker sought permission to expand that base.

Prior to the meeting, the FDA had raised a number of concerns with OP-1, including patient immune response and the results of a clinical study in which patients who underwent surgery with an autograft actually experienced better outcomes.

According to the FDA advisory committee, control subjects in the study “had a higher rate of bone formation” than those who had received the OP-1 Putty.

Stryker’s response to those findings involved claims that the medial bone formation associated with OP-1 Putty could not be effectively assessed with the plain film techniques used at 24 months in the study. Stryker claimed the bone growth that went unseen on patients at the 24-month mark during X-rays would be seen at the 9-month mark on patients who underwent CT scans.

Stryker also claimed that the long-term results for autograft patients were similar to those who received OP-1 Putty. Those on hand to help present Stryker’s case talked extensively about the efficacy of the putty as well as the validity of the study results presented.

“What struck me when I was looking at these data were the trends for improved neurologic success,” said Michael G. Fehlings, MD, PhD, FRCSC, director of the Neural and Sensory Sciences Program at the University Health Network in Toronto.

“As a clinician, when I look at this, I see a product that seems to have good long-term outcomes based on disability index scores. It appears to be safe, be associated with good neurologic outcomes, and is associated with biomechanical evidence of long-term stability,” he said.

While some panel members commended the presentation, ultimately they remained almost unanimous in their assessment: Evidence in support of OP-1 Putty was lacking when compared to the study results and the concerns that went unanswered.

“I’m concerned about the post-hoc analysis that had to be done to yield a positive result,” John Kirkpatrick, MD, a voting member of the panel, said during the discussion period. “I continue to have concerns about, as [Raj Rao, MD] mentioned, whether fusion happens if there’s bone there. I have significant concerns when both the statisticians on the panel have issues with statistics. “I still have a concern over the potential of a drug having a relatively low incidence but a catastrophic adverse event.”

The decision is a blow for Stryker. However, the company indicated immediately after the meeting that it would proceed according to whatever ruling the FDA will hand down.

“We are very disappointed by the FDA advisory panel’s vote,” Stryker officials stated in a release. “We believe the clinical evidence that we submitted and the long history of OP-1’s use demonstrate OP-1’s proven safety record.

“We will continue to provide support to our current customers and their patients, and [we] are committed to doing so in full compliance with FDA regulations and requirements as we review our strategic options related to OP-1,” according to the statement.