The Panel Meeting
The company ran out of time during the Panel meeting to answer all the questions posed by Panel members and FDA staff. With unanswered questions, there was still a path forward.
Hagan said there were approximately 50 of those questions from the Panel that remained unanswered at the time that the Panel was asked to vote. “In retrospect,” Hagan told us, “we simply ran out of time to share the data that had been carefully prepared to answer the Panel questions. The data and slides were ready to share, there was simply no opportunity to respond.”
The subsequent questions posed by FDA gave the company an opportunity to present more evidence regarding safety. For instance, the company was able to provide data from 334 additional patient time points which showed a 50% treatment differential between the Barricaid group and the control group.
“Fifty percent is a high number, especially considering the high rates of reherniation and treatment costs of patients who have to go back for second, third and even fourth surgeries,” said Hagan.
Through a patient and consistent interaction with FDA staff, Intrinsic and the team at MCRA (Musculoskeletal Clinical & Regulatory Associates) built a successful case for safety. In the end, the FDA staff saw the forest for the trees.
Lessons
We asked Hagan what lessons he took away from this FDA experience and what advice would he give his colleagues who may experience the same thing in the future.
First, said Hagan, “listen actively to the questions posed by FDA staff.”
Second, “take extra time with the FDA review team to clarify and confirm exactly what they want and what they think they are hearing from you.”
And finally, “Be patient. Very patient.”
“I have a positive view of FDA,” said Hagan. “Other than the time limitation of the Panel meeting, this process worked like it is supposed to work. The FDA worked very hard, spent huge amounts of time and were extremely responsive in the scientific process. It was extremely difficult and cost us one year, but it was fair.”
The Evidence
Before we close this happy story, let’s look at the safety issues Hagan and his team had to patiently address with the Panel and FDA staff.
According to the FDA approval document, the device is “indicated for reducing the incidence of reherniation, and reoperation in skeletally mature patients with radiculopathy (with or without back pain) attributed to a posterior or posterolateral herniation, and confirmed by history, physical examination and imaging studies which demonstrate neural compression using MRI to treat a large anular defect (between 4-6 mm tall and between 6-10 mm wide) following a primary discectomy procedure (excision of herniated intervertebral disc) at a single level between L4 and S1.” Lumbar discectomy is considered to be the largest unaddressed market in spine.
The FDA Panel voted 9-5 against recommending approval due to safety concerns. The Panel members’ safety concerns stemmed from the FDA staff noting to members that CT imaging showed bone changes to the vertebral endplates for some of the Barricaid patients.
Eighty-eight percent of the patients receiving Barricaid had endplate changes versus 40% of control patients. The control patient’s changes were slightly smaller on average and appeared to stabilize sooner than the Barricaid patients. The Barricaid endplate changes were larger and had a distinctive radiographic feature—according to the FDA’s radiologist.
But when Hagan and team were able to address all the leftover questions from the panel meeting, they were able to show that endplate change stabilize and that the use of Barricaid cut recurrent disc herniations, re-operations and serious adverse events by roughly 50%, a difference that was highly statistically significant. “These measures,” added Hagan, “clearly have a meaningful impact on patient quality of life.”
