Valuation and Timelines, page-19

I have been skeptical since Wayne first floated the idea in a photo of a presentation on Twitter and am even more skeptical after listening today to a webinar the FDA did a 4 years ago after the HDE guidelines were updated.

A few takeaways from the webinar:

- The HDE pathway allows for more uncertainty in the data than the approval pathway but a comment was made that less uncertainty is allowed for a mortality endpoint than for an endpoint that's "only" pain. As a primary endpoint for any TAVR trials will be mortality, that tells you proving safety is a huge hurdle for TAVR and other life-sustaining devices.

That's why pivotal TAVR trials need around 1000 patients, because the population has to be large enough to guarantee safety to a statistical significance. This likely IMO also means that the FDA would not be likely to approve an HDE for a life-sustaining device like the DurAVR when there are approved options, even if the DuAVR can show performance superiority, because it's probably not worth the risk from the FDA's point of view.

- There was another comment about trial size necessary for HDE submission where the FDA expert said that he's seen pivotal trial sized studies for patient populations approaching the 8,000 patient maximum. That's anecdotal but it does indicate that larger addressable patient populations need larger trials and, by my extrapolation, the amount of valve in valve procedures performed in the US this year will likely exceed 8,000. This means we could need a very large trial size to address that large of a potential patient population.

Having enough devices implanted to prove safety will always be an issue, and it may very well require a minimum of 900 procedures done in trials, but Wayne does continue to prominently mention valve-in-valve and an HDE seems to be the most likely pathway, so we'll see. I'm very skeptical though. My timeline is still that we'll need to wait for a general approval in the first half of 2028 but I'm just some guy on the internet and I know the team at Anteris is working creatively to try to expedite things if possible, and the FDA is open to consultation.

Here's that webinar: