By Bob Marshall, Chief Editor, Med Device Online
To De Novo, or not to De Novo, that is the question: whether ‘tis nobler in the mind to suffer the slings and arrows of outrageous regulations, or to take arms against them. With all due respect — and an apology — to William Shakespeare, Hamlet’s soliloquy seems to capture, all too clearly, the lot of Avenu Medical and its minimally invasive approach to AV fistula creation.
Following three years of product development, Avenu’s Ellipsys Vascular Access System languished for nearly five additional years through the De Novo regulatory pathway before finally achieving a nod from the FDA in the middle of this year.
“The De Novo pathway was supposed to be a better way for low-risk new technologies to come to market, rather than the traditional PMA. Things didn’t turn out that way,” commented Avenu Medical President Mark Ritchart.
One might expect an arduous path for a startup medical technology company, but this is not Ritchart’s first “play.” Ritchart and Avenu VP of Marketing Ed Chang have worked together numerous times as serial entrepreneurs, creating solutions for unmet clinical needs. The pair previously achieved success in developing the Mammotome, the first vacuum-assisted biopsy system for early detection of breast cancer, the AutoCuff System for total arthroscopic repair of torn rotator cuffs, and devices for ACL reconstruction. Their previous companies were acquired by the likes of Ethicon Endo Surgery (Johnson & Johnson), ArthroCare (Smith & Nephew), and Zimmer Biomet.
Ritchart and Chang created Avenu Medical to address a significant problem: 36 percent of surgical fistulas never become functional and are never used. The procedure is associated with a significant, and unsightly, amount of morbidity. Thus, patients shy away from traditional fistula surgery, ending up crashing, and having to depend on catheters.
“Our physician co-founder came to us and said, ‘there’s got to be a better way to do this in a minimally invasive manner.’ So, we set off with the problem statement, ‘if you could create an AV fistula in the same length of time that it takes to draw blood, with the same morbidity, you would really have something,’” Ritchart explained. “We began a three-year period of product development thinking about how we could get in there without an incision and make a working fistula.”
See the result of the Avenu Medical development effort in this animation.
Avenu Medical had no problems recruiting patients for its clinical study following development of the Ellipsys; in fact, the company had to stop enrollment at 117 patients, per the protocol, even though many more patients volunteered. Another advantage of the procedure is that it does not need to be performed by a surgeon, broadening its availability to more patients.
“More than 95 percent or surgical fistulas today are done in a hospital operating room. We treated all 117 patients for the Ellipsys study in doctors’ offices or physicians’ labs,” Chang said.
Ellipsys also reduces the time required for an AV fistula to become functional for a dialysis patient: the national average is 136 days for surgical fistulas, while the U.S. clinical trial for Ellipsys showed 100 days. Data from European use of Ellipsys (which began two years ago) shows all patients having functional AV fistulas in 30-35 days. Longer-term success rates are over 90 percent after one year of using the AV shunt for dialysis. Some patients from early studies in Columbia and Mexico continue to show patency of the fistula four and five years after the procedure was completed.
In spite of Ellipsys’ success, Avenu Medical’s negative experience with FDA’s De Novo process stands in stark contrast to that of Curetis, a company I wrote about earlier this year. Oliver Schacht and Johannes Bacher — Curetis' CEO and COO, respectively — spoke rather glowingly of the cooperation and responsiveness they experienced in navigating the De Novo process for their Unyvero System and lower respiratory tract infection application cartridge. But Ritchart and Chang noted that the De Novo pathway is complex, and requires more time and effort, while opening the door for competitors to file less burdensome 510(k) submissions using the original De Novo approval as a predicate.
“All good startup companies begin with the identification of a problem statement. What problem are you solving and why are you going to go after it? And, if you solve it, will the solution pay for the R&D effort?” Ritchart concluded. “Buried in that equation is a new variable: the FDA and the De Novo pathway. If you come up with a good problem statement and have a good team, ultimately, you’re going to be successful if you have enough money and time. The problem is, these new technology plays that fit into the De Novo pathway are most likely an eight-year process.”
Added Chang, “you also need to find a good, survivable market… to have backers invest in your idea, and eventually establish reimbursement.”
If this is the last scene for Ritchart and Chang, at least they will retire from medical device development knowing their current effort, the Ellipsys Vascular Access System (or “band-aid fistula,” as it is affectionately known by dialysis patients), solved a clinical need for millions of patients that had been unmet for 52 years. Unfortunately, overburdensome regulations will result in fewer entrepreneurs out there, willing and able to take risks, striving to save lives and to improve the quality of life for patients around the globe