The Neurological Devices Panel (the Panel) met on Tuesday, August 5, 2003 in Gaithersburg, Maryland, to make a recommendation to the Food and Drug Administration (FDA) on the approvability of the Micro Therapeutics, Inc.’s PMA, P030004 for the Onyx® Liquid Embolic System (LES) intended for pre-surgical treatment of brain arteriovenous malformations (AVMs). Brain AVMs are relatively rare cerebrovascular lesions, and there is great individual heterogeneity among AVMs. The Panel membership for this meeting consisted of two neurosurgeons, three interventional neurological radiologists, two neurologists, an internist/toxicologist, a statistician, a consumer representative, and an industry representative.
The sponsor presented its information on the safety and effectiveness of the device, and FDA reviewers summarized the data in the PMA. Three Panel members, an internist/toxicologist, an interventional neurological radiologist, and a statistician then gave their perspectives on PMA data. After deliberations on the information in the submission, the Panel considered FDA’s questions.
The Panel then voted six to one with one abstention that FDA approve the PMA with conditions. The recommended conditions of approval are as follows:
- Evidence of angiotoxicity and vasculitis should be investigated in surgically excised Onyx® LES specimens and in a small number of post-mortem samples.
- Evidence of hemolysis should be investigated in a small number of patients.
- The labeling should be revised to include a statement that there were more instances in which the user had difficulty removing the delivery catheter for the Onyx® LES device than for the n-BCA device; the n-BCA device is the control device for the PMA study.
- The labeling should be revised to include a statement that all of the study patient deaths occurred in the Onyx® LES group, and that while these deaths could not be attributed to the device, the possible role of Onyx® LES in the patients’ deaths, if any, is unknown.
- The sponsor should conduct a post approval study of patients who did not have their Onyx® LES-treated AVM completely surgically excised (3-5 years follow-up recommended) and of patients who did have surgical excision of their Onyx® LES-treated AVM (1 year follow-up recommended).
- The training program should be mandatory for all users. It should include the following:
- Hands-on training using in vitro and in vivo models under fluoroscopic visualization, and
- Newly trained physicians should have one proctored case; if the physician’s first case is deemed a failure, the physician must conduct another proctored case.
- The sponsor should make a concerted effort to collect and report European Onyx® LES data to the FDA.
The Panel member who abstained recommended that FDA review the results of the sponsor’s recently prepared covariate analysis of the safety data.
Contact: Janet L. Scudiero, Executive Secretary, at 301-594-1184 ext. 176, or firstname.lastname@example.org.
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