Letter: Food and Drug Administration Approval of the Wove Endobridge Device: What do the Numbers Tell Us?

To the Editor: On December 31, 2018 Sequent Medical received FDA (US Food and Drug Administration) approval for commercialization of the Woven Endobridge Device (WEB device, Sequent Medical Inc, Aliso Viejo, California) in the United States.1 The WEB device, an endovascular device for treatment of intracranial aneurysms,2 is part of a new generation of medical devices for endovascular treatment of intracranial aneurysms with presumed better efficacy and extended indications.3-6 FDA approval for a device is crucial for medical device companies to enter the market and obtain market share. The WEB device was approved for aneurysms at the “middle cerebral artery (MCA) bifurcation, internal carotid artery (ICA) terminus, anterior communicating artery (AComm) complex, or basilar artery apex for the endovascular treatment of adult patients with saccular, wide neck, bifurcation intracranial aneurysms with dome diameter from 3 mm to 10 mm and either neck size 4 mm or greater or the dome-to-neck ratio is greater than 1 and less than 2.”1 The approval for the WEB device was based on a the “WEB-IT trial” which is a Premarket Approval (PMA) study that is necessary for Class III medical devices (devices that “usually sustain or support life, are implanted, or present potential unreasonable risk of illness or injury”).7,8 Of note, the WEB device has been available in Europe since 2011 as such a trial was not necessary before commercialization based on local legislation at the time there.2 Nevertheless, the WEB device has gained some traction in several centers in Europe.9-11 There are, however, potential issues regarding safety, efficacy, and manner of introduction of the WEB device. Several manufacturer-sponsored single-arm prospective trials have been conducted for the WEB device to evaluate its safety and efficacy, both in the United States and Europe.6,7,12 Unlike endovascular coiling, none of these trials made a methodologically rigid comparison with the current standard therapy for wide-neck aneurysms: clipping.13-16 It therefore remains unclear which treatment strategy is superior with regard to functional and treatment outcomes or whether the WEB device offers any true advantages. The studies that evaluated the WEB device were conducted relatively recently and long-term outcomes are not available.6,7,12 In the WEB-IT trial 18 out of 143 (12.6%) patients had a recurrence at 1 yr,17 which is slightly lower compared to rates reported by European trials.6,12 Similarly, complete occlusion was only achieved in 77 out of 143 (53.8%) patients.17 This rate is relatively low when compared to occlusion rates from wide-neck aneurysms from the BRAT trial with 6 yr of follow-up (complete occlusion 91.8% at 6 yr for clipping).16 Similarly, retreatment was necessary in 8 out of 143 (5.6%)17 patients after 1 yr in the WEB-IT trial compared to none in the BRAT trial (0 out of 136 wide-neck aneurysm patients).16 Retreatment of previously treated intracranial aneurysm patients may be challenging and come with poor outcomes.18 Some have suggested that retreatment of a WEB device treated aneurysm is safe and effective, but this is based on retrospective data with small numbers.19,20 One small retrospective study that evaluated large aneurysms (≥10 mm) treated with WEB devices described a retreatment rate of 7 out of 15 patients of which 2 resulted in severe complications and one mortality.21 One of these retreatments was surgically which proved to be extremely challenging.21 Although the WEB device is officially not approved all types of intracranial aneurysms in the US, we fear that the recent approval might result in “off-label use” of these devices in eg large aneurysms patients. For instance, Pipeline embolization devices (Medtronic) are being used off-label for various indications.22 One may still argue that despite potentially inferior treatment related outcomes, functional outcomes will not be inferior as seen with coiling and clipping.16 This is at this moment no more that speculation as long-term functional outcomes that compare the WEB device with other treatment modalities are not available. To our knowledge, no trial that aims to compare the WEB device to other treatment modalities in a methodologically sound manner is being conducted. Perhaps if the WEB device had been introduced according to the Idea, Development, Exploration, Assessment, Long-term study criteria for devices (IDEAL-D), which places an emphasis on rigorous evaluation data on outcomes, outcomes of such a trial would be available.23,24 However, there is currently no incentive or obligation for medical device manufacturers to follow guidelines that would require more evaluation or trials, both in the US and Europe. From a manufacturer's perspective, following frameworks such as the IDEAL-D for methodological sound introduction of devices could - at least on the short term - potentially only limit shareholder value due to increased costs. There is even the possibility of no return on investment if more rigorous evaluation would result in denial of commercialization, proven inferiority to other treatment modalities, or a lack of trust in the device among physicians and patients. Selection of the optimal treatment strategy will remain at the discretion of physicians responsible for treatment of intracranial aneurysms and physicians should take complete occlusion and potential retreatment rate into consideration. We believe the WEB device may only be useful when no proven options are deemed feasible. Physicians should familiarize themselves with the results of available trials and should present these to the patient and his or her family to come to an optimal treatment strategy. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.