By: Susan Lubejko PhD and Abigail Copeland PhD, Regulatory Affairs Specialists at Mittal Consulting
Over the past year, two neurovascular implant companies, Sonorous Neurovascular and VS3 Medical, received Breakthrough Designation for self-expanding stents to treat pulsatile tinnitus caused by venous sinus stenosis, a narrowing of the large cerebral veins that transport blood from the brain to the heart. The narrowing of these veins creates turbulent blood flow in the vessel which is heard as a “whooshing” sound by affected individuals that can be debilitating. Interestingly, stenting as a treatment for pulsatile tinnitus is already integrated into clinical practice but is currently used “off label” as existing stents are intended for the carotid artery or peripheral veins. Here, we examine how these two competitors in the pulsatile tinnitus space are both utilizing the Breakthrough Program in an effort to bring off label stenting on label.
Sonorous Neurovascular and VS3 Medical propose stents that are specifically designed for intracranial anatomy to treat venous sinus stenosis, which may mitigate challenges associated with off-label stents. In addition to the benefits of purpose-built engineering that addresses specific challenges associated with a delicate intravascular procedure, there are significant strategic advantages for device Sponsors bringing a treatment into on-label use. As the devices pursue marketing authorization, clinical evidence will be gathered specifically on the use of the intracranial stents for the purpose of treating pulsatile tinnitus, supporting demonstrable safety and effectiveness, clinical best practices, and standardized treatment protocols. Such clinical evidence may encourage further adoption of stenting by additional physicians and hospitals who might have been hesitant to adopt off-label use and may strengthen reimbursement arguments, thereby expanding accessibility for patients. Following authorization, Sponsors will be able to make direct marketing claims about the use of these devices for treating pulsatile tinnitus and will have commercial advantage over competing devices without authorization for the intended use.
Despite off-label stent use, there are no existing FDA authorized devices specifically labeled for treatment of pulsatile tinnitus, the symptoms of which are often addressed by blood-pressure drugs and behavioral therapy. This is likely why Sonorous and VS3 were able to successfully argue for Breakthrough designation, whereas some Sponsors may be hesitant to apply for the program due to the existence of similar, off-label techniques used in clinical practice. Encouragingly, we see here that refinement of existing clinical practice in a particular field is supported by FDA’s accelerated regulatory pathways. As with any Breakthrough request, Sponsors must show that their solution is better able to treat patients with debilitating disease than what is currently available. Both companies here report having conducted first-in-human clinical studies, which were likely used to demonstrate potential clinical success of the new stents for pulsatile tinnitus. More interestingly, this also suggests that the existence of an adjacent off-label technology in a clinical field doesn’t necessarily absolve Sponsors of the need to demonstrate their device clinically, the norm in recent years to obtain Breakthrough designation.
Sonorous Neurovascular and VS3 Medical’s devices illustrate why Sponsors should continue innovating in clinical spaces where imperfect, off label solutions have become common. FDA’s acknowledgement of both devices through a Breakthrough designation indicates excitement about advancing efforts to improve the clinical options available for pulsatile tinnitus and demonstrates regulator support for refinements of clinical practice. For neurotech Sponsors in other areas, these examples point to FDA’s recognition of solutions to off label clinical options and demonstrate the necessity of continued innovation upon the standard of care, ultimately providing the best access for patients through well-validated and purpose-built solutions.