FDA says “no” to Barricaid for partial annulus replacement in patients with herniated discs
INTRINSIC LOSES FDA VOTE FOR ANNULAR CLOSURE DEVICE (Orthopedics This Week)
Even before the committee voted, it was not looking good for Intrinsic Therapeutics Inc. and its annular closure device for discectomy patients, Barricaid.
Then the committee voted, and Barricaid’s fate was sealed.
By a margin of 9 to 5, the committee said that there was insufficient evidence of Intrinsic’s annular closure device’s safety when implanted to prevent disc re-herniation. It did vote that Barricaid was effective but, when asked whether the benefits outweighed its risks, the committee said “no” by a vote of 8 to 5, with 1 abstaining.
The vote by the FDA’s Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee occurred on December 12, 2017.
FDA Staff Concerns
But, really, the committee’s outcome was probably pre-ordained based on the FDA staff instructions where both the study methodology and safety were called into question.
Barricaid’s study, which was a prospective, randomized investigation, recruited 554 discectomy patients of which 276 were randomized to Barricaid after a discectomy while the remaining 278 received discectomy alone.
The patients were followed for 24 months. The study’s primary end points were re-herniation and a composite of the Barricaid’s safety and efficacy.
According to the FDA’s instructions to the panel, Intrinsic deviated from its study plan and enrolled patients with a lower risk of re-herniation. Quoting from the FDA’s letter:
“The sponsor planned to … include subjects with an increased risk of disc re-herniation (i.e., large annular defects defined as between 4-6 mm tall and 6-12 mm wide post-discectomy).”
“It appears that … the enrolled study population appeared to differ from prior literature reports regarding the incidence of “at risk” disc herniations types.”
“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.”
“The majority of 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 sponsor.”
FDA’s staff also raised questions about the high rate of lesions on patient’s endplates from Barricaid. Eighty-eight percent of the patients receiving Barricaid had endplate lesions versus 40% of control patients. Furthermore, the control patients’ lesions were smaller and appeared to stabilize sooner than the Barricaid patients’ lesions. The Barricaid patients’ lesions were not only larger, but they had distinctive radiographic features.
Intrinsic checked on the lesions and found that they had no correlation to measured study outcomes.
This FDA panel rejection comes just seven months after Intrinsic raised $49 million in a debt/equity deal to fund the commercialization of Barricaid.
That particular round consisted of a $28 million equity financing led by New Enterprise Assoc. and Delos Capital, plus a $21 million debt facility with CRG. Other backers included Greenspring Associates, Quadrille Capital and a “corporate strategic”.
Back in December 2016, when Intrinsic revealed an $18 million raise in a regulatory filing, the company had filed its pre-market approval application with the FDA for the Barricaid device.
Back to the drawing board.
An FDA advisory panel voted 5 to 8 against recommending approval for Intrinsic Therapeutics’s Barricaid prosthesis designed for partial annulus replacement in patients with herniated discs, according to a MedPage Today report.
The negative recommendation came based on concerns over the safety of the device, including breakage rate and certain endplate lesions of unknown origin. The same panel voted 12 to 1 in favor of the device’s efficacy, according to the report.
“There was a high rate of breakage of the device, a high rate of migration, and [there was] the unknown nature of [some endplate] lesions,” panel member Dr. Eli Baron of the Cedars Sinai Spine Center in Los Angeles said, according to the report.
Other panel members disagreed, and saw the device as having some minor concerns.
“[The device is] reasonably safe, and I think the major concerns centered around the endplate lesions and while there were some theoretical concerns about harbingers of device failure … the number of lesions observed was sufficient to reassure me that there is nothing catastrophic about the devices,” Dr. Ty Subhawong of the University of Miami who voted in favor of the device said, according to the report.
The Barricaid implant is a polymeric mesh that is designed to sit at the posterior intervertebral disc space and is connected to a metal anchor that is attached to the vertebral body, according to an FDA briefing document.
The device is intended an adjunct for lumbar limited discectomy to replace missing or damaged parts of the anulus to prevent re-herniation, disc collapse, the return of sciatica and potentially to help stave off low back pain.
The system was tested in a nearly seven-year-long study, spanning from December 2010 to May 2017, which enrolled 554 patients at 21 sites across northwestern Europe, MedPage Today reports.
Intrinsic Therapeutics had originally sought investigational device exemption from the FDA for a US trial, but the application was denied due to safety concerns, according to the report.
Results from the European trial indicated that 50.8% of Barricaid patients had no reherniation at 24 months, higher than the 30.1% rate in the control group. A total of 27.8% of Barricaid patients also achieved the composite endpoint when compared to 18.1% in the control cohort, according to MedPage Today.
Patients who received interventions with the Barricaid had an 93.1% rate of adverse events, higher than the 78% reported in the control group. Serious adverse events were 38% for Barricaid patients and 41% in the control, according to the report.
A major concern amongst the panel was endplate lesions, which were reported in 88% of Barricaid patients but only 39% in the control cohort, MedPage Today reports.
In May, Intrinsic Therapeutics said it raised a $49 million debt-and-equity round for the Barricaid annular closure device for discectomies that it’s developing.