Although FDA doesn't have to follow the recommendation of its advisory committees, a negative panel vote is never a good sign for a company hoping to bring a new device to the market.
Intrinsic Therapeutic learned the hard way Tuesday that it's usually best if clinical trials follow the protocol that was initially communicated to the agency. Changes to the device trial, along with other concerns FDA staff raised, caused an advisory panel to vote against recommending approval for Intrinsic's Barricaid prosthesis, according to a MedPage Today report. The device is designed for partial annulus replacement in patients with herniated discs.
FDA staff raised concerns in a briefing document prior to the advisory panel meeting. In the document, the agency noted that Intrinsic planned to enroll a study population that includes people with an increased risk of disc reherniation who would potentially benefit from a permanent implant to prevent reherniation compared to discectomy alone. Yet, when staff reviewed the submitted data it appeared that the enrolled study population didn't exactly match that description, based on published literature regarding the incidence of "at risk" disc herniations.
For example, the Barricaid study had a much lower number of fragment-fissure type anular defects which are associated with a low rate of recurrent lumbar disc herniation in the enrollment population. Additionally, the agency found that most of the study subjects appeared to receive anulotomies (box and cruciate shape) during the discectomy procedure, prior to randomization, which suggests surgical resection of disc annulus may have gone beyond the extent required for performing a limited discectomy as defined by the company.
FDA staff wanted to know, among other things, if the differences between the limited discectomy procedures reported in the literature compared to the treatment received by those enrolled in the Barricaid study. Then, the agency wanted the company to discuss whether the differences had an effect on the clinical outcomes, especially with respect to reherniation rates and subsequent surgical interventions in the control group.
Staff also raised concern about the 88% of treated patients with an end-plate lesion (EPL) compared to the 40% of control group patients with an EPL. Also, the control patients with EPLs have lesions that are smaller, appear to reach stability sooner, and present features more in line with Schmorl's nodes, according to the document. The EPLs of the Barricaid patients, on the other hand, were larger, progress in size faster, have radiographically distinct features (e.g., lytic features and a location in proximity to the mesh), and show signs of mesh subsidence into the lesion. However, based on the secondary analyses the company performed, "there does not appear to be a correlation between the presence of EPLs and measured clinical study outcomes," agency staff noted.
Intrinsic Therapeutics said its device is designed to close large anular defects so that the orthopedic surgeon can minimize the amount of disc removed. It consists of a piece of polyester fabric anchored to an adjacent vertebral body.