Shockwave Medical Inc., which is focused on intravascular lithotripsy (IVL) to treat severely calcified cardiovascular disease, saw its stock value rise Friday (NASDAQ:SWAV), eventually closing at $78.22, up $3.47, or 4.64%, following the presentation of positive results from the Disrupt CAD III trial.
Disrupt CAD III, a prospective, multicenter, single-arm, global IDE study, investigated the Shockwave Coronary IVL System in de novo, calcified, stenotic, coronary arteries prior to stenting. It enrolled 384 individuals at 47 sites in the U.S., France, Germany, and the U.K., including 100 patients in an optical coherence tomography (OCT) sub-study. All data were core-lab adjudicated.
According to the company, the technology aims to minimize trauma to soft tissue, optimize outcomes while reducing complications and cost escalation, as well as simplify procedures.
With that in mind, the study, which was based on the single-arm ORBIT II IDE study of orbital atherectomy to develop performance goals that would allow the U.S. FDA to evaluate the safety and effectiveness of IVL in a single-arm study, met the primary safety and effectiveness endpoints with a 30-day freedom from major adverse cardiovascular events (MACE) rate of 92.2% (p<0.0001). That is against the safety performance goal of 84.4%, which Wells Fargo’s Larry Biegelsen highlighted. He also pointed out the procedural success rate of 92.4% (p<0.0001) compared with the effectiveness performance goal of 83.4%.
The individual components of the 7.8% MACE rate included low rates of cardiac death (0.5%), myocardial infarction (7.3%), and target vessel revascularization (1.6%) at 30 days following the index procedure. Freedom from any serious angiographic complication following IVL delivery and at any point during the procedure were 97.4% and 96.9%, respectively.
On the primary effectiveness endpoint of procedural success, the individual endpoints included successful stent delivery in 99.2% of patients, a residual stenosis of less than 50% in all cases, and no in-hospital MACE in 93.0% of patients.
Results were presented at a late-breaking clinical session at the virtual 2020 Transcatheter Cardiovascular Therapeutics conference and published simultaneously in the Journal of the American College of Cardiology (JACC).
According to the authors of the study, the results bolster IVL. Although researchers saw satisfactory results in earlier small, single-arm, nonrandomized studies, these had their limitations. Now, the researchers have concluded that IVL “safely and effectively facilitates stent delivery and optimizes stent expansion in patients with severely calcified coronary lesions.” Long-term follow-up will be needed to determine the durability of benefit, they added.
The Santa Clara, Calif.-based company said CAD III represents one of the most challenging series of calcified lesions ever treated in an investigational device exemption trial. The average calcium lesion length was 47.9 mm, and the average calcium arc was 292.5 degrees, with a thickness of 0.96mm at the site of maximum calcification, as measured by OCT.
“The correlation between calcium severity and poor percutaneous coronary intervention outcomes is well established and is a challenge we face on a daily basis in the cath lab. Given the severity of lesion and vessel calcium that was present in CAD III, it makes the findings of the study even more significant and noteworthy,” said study co-principal investigator Dean Kereiakes, medical director of The Christ Hospital Heart and Vascular Center and the Christ Hospital Research Institute and professor of clinical medicine at Ohio State University. “The high rate of procedural success, combined with the low rate of [MACE] in CAD III, not only met the performance goals, but it also surpassed our expectations as investigators.”
The results were discussed during an investor call held the same day of the presentation, with Morgan Stanley’s David Lewis about the commercial strategy for next year and how investors should think about the market opportunity for coronary.
Shockwave CEO Doug Godshall replied that the data had landed right where the company had hoped, with the MACE rate falling below 10%. That figure came despite the complex lesions involved. “So, essentially, the same outcomes, tougher patients, very encouraging and certainly reinforces our decision to ramp up our commercial footprint and production volumes in advance of an anticipated approval in the first quarter of next year. So, no real update other than we are tracking to plan, and our plan is to make us available to help as many patients in the U.S. as we can over the course of 2021,” he concluded.
For his part, Biegelsen was positive following the presentation and saw a bright future for the technology. “Given the compelling CAD III data and our clinician checks, we expect uptake of SWAV’s IVL technology to ramp faster than we originally expected in the U.S.,” he wrote, adding “[w]e expect SWAV’s IVL to expand the U.S. market and also take some share from atherectomy.”
He went on to explain that Shockwave previously pegged the total addressable market opportunity at more than $2 billion globally for IVL in CAD.
This is not the first time Biegelsen has expressed enthusiasm about Shockwave’s chances. In a September note, he wrote that results from this study should be favorable vs. previous atherectomy studies, including the Cardiovascular Systems Inc. (CSII)-sponsored ORBIT II study. That study evaluated patients with severely calcified coronary lesions treated with Diamondback 360 coronary orbital atherectomy system classic crown prior to stent implantation.
“We believe adoption of IVL for coronary will be strong given improved safety, ease of use and broader utility compared to atherectomy. In addition, we expect IVL to receive enhanced reimbursement for coronary in 2021,” Biegelsen said.
Danielle Antalffy with SVB Leerink Research noted there has been a lot of noise around potential competition with CSII’s orbital atherectomy system, but there are differences, particularly with pre-dilation rates and stenosis. “Overall, we continue to see SWAV's IVL as market expansionary vs. directly competitive with CSII (Cardiovascular Systems, Inc.), and these data seem to point pretty clearly to a very different subset of patients between devices,” she wrote.