Single-product medical technology companies live or die by their clinical data, and in the case of Claret Medical the latter path is beckoning. The company’s Sentinel device, designed to filter and remove embolic debris released during endovascular procedures including transcatheter valve implantation, has failed in its pivotal US trial.
The private company has no other technology to fall back on, and the PMA application it filed in September looks unlikely to meet with success. With little prospect of a trade sale thanks to the trial miss, and limited cash in the bank, it is hard to see much of a future for Claret.
A pivotal trial failure is not always a barrier to US approval, as the green light for St. Jude Medical’s Amplatzer PFO Occluder this week shows (Heart plug approval a minor win for St. Jude, October 31, 2016). But the circumstances are very different.
The Sentinel device consists of two filters within a single catheter. They are positioned in the brachiocephalic and the left common carotid arteries before a transcatheter aortic valve replacement (TAVR) procedure, and are withdrawn into the catheter and removed afterwards. Stroke is a complication of TAVR associated with increased mortality and morbidity.
Claret’s pivotal trial, also known as Sentinel, enrolled 363 patients undergoing TAVR to treat severe symptomatic aortic stenosis. A third of the patients were randomly assigned to a safety group in which they only received the Sentinel, a third to a test group in which they received the Sentinel and underwent imaging and the final third to a control group that only received imaging.
Data presented as a late-breaker at the Transcatheter Cardiovascular Therapeutics (TCT) meeting yesterday showed that the trial failed on the primary efficacy endpoint. In the areas of the brain protected with the Sentinel, the average size of the new lesions formed after TAVR was 102.8mm
The primary safety endpoint was major adverse cardiac and cerebrovascular events at 30 days post-procedure. The rate of these events was 7.3% in the combined device and safety arms, not statistically different from control, at 9.9%.
Despite the finding of histopathologic debris – including thrombus, calcification, valve tissue, artery wall and foreign material – within the Sentinel’s filters in 99% of the patients, the rate of strokes at 30 days were not significantly different in the device and safety arms versus the control arm, at 5.6% vs. 9.1%.
There are some findings to which Claret can pin its hopes. While median new lesion volume in the protected areas was not significantly different between the device and control arms, researchers identified confounders including the type of transcatheter valve used – two Edwards valves and two Medtronic products were used in the trial – and baseline MRI lesion volume, a marker of baseline cerebral disease burden. After adjusting for these factors, use of the Sentinel did result in reduction of new lesion volume on MRI.
It is true that, while a safety failure would have done for Sentinel’s chances of FDA approval, the agency does tend to look more favourably on efficacy misses, especially when, as in this case, the trend was in the right direction. Moreover, there is no device approved to protect against strokes caused by endovascular procedures.
If approval is not forthcoming, Claret is in trouble. Its last infusion of cash was an $18m series B round in 2014, and it will be hard to drum up more investment to fund another study. And, assuming that the company’s endgame is a trade sale, as is the case with the vast majority of single-product medtech groups, it has little to hope for here either.
If lightning does strike and the device is approved, Claret’s troubles will not be over. It will then have to persuade doctors of the Sentinel’s utility, and based on the results of this study that might be a hard task.
|Claret Medical's VC funding|
|Date||Round||Investment ($m)||Investor Name|
|August 21, 2014||Series B||18.0||Santé Ventures, Lightstone Ventures and Easton Capital Investment Group|
|June 28, 2013||Undisclosed||3.6||Undisclosed|
|October 31, 2011||Series A||3.4||Undisclosed|
|March 1, 2011||Undisclosed||0.3||Undisclosed|
|November 2, 2010||Undisclosed||0.2||Undisclosed|
|June 2, 2010||Seed capital||1.3||Undisclosed|