PARIS – Advancing with the U.S. Food and Drug Administration sometimes means taking a step backwards.
Edap Tms SA, based in Lyon, France, said it has withdrawn a 510(k) application for its Focal One device, a next-generation high-intensity focused ultrasound (HIFU) platform for prostate tissue ablation in order to add clinical data and resubmit the application.
CEO Marc Oczachowski told BioWorld MedTech the new filing will be made "in a few weeks' time, in the third quarter."
In the original submission, he explained, the biopsy protocol was not comparable to the predicate device, which used a strategy of systematic biopsy for every patient in that trial.
In the Focal One trial data, biopsies were only performed "for cause," where there is a suspicion of recurrence on follow-up MRI imaging studies.
"Under FDA rules, if a patient has not been biopsied, it is considered a failure. The fact that we were not taking biopsies under the protocol meant there were actually more successes than failures," he explained.
Oops. Never mind. Edap scrambled across study sites in Sweden, Germany and France where biopsies had been systematic on each patient at six months and one year.
Problem solved, Oczachowski said the company brought the new data to the FDA only to be told the agency cannot accept it within the framework of the existing 510(k) application.
Ouch. The FDA suggested pulling the original submission, he said, and the company will resubmit the application, identical with the original, except for the addition of the new clinical data.
Nasdaq investors sent the company's stock tumbling 5.5 percent the day after it announced it was pulling the application, though the share price recovered and one week later had returned to its pre-announcement level.
"Investors understand we are resubmitting 510(k) and don't believe we will be losing much time in the application process," he said.
Long history in HIFU
Edap is the pioneering company in ultrasound-guided HIFU since 1979, eight years before a competitor arrived, according to the Focused Ultrasound Foundation based in Charlottesville, Va.
In 2016, the company generated €35.6 million (US$41.8 million) with revenue from the HIFU division increasing 63 percent over 2015.
The Focal One platform brings new capabilities to prostate cancer therapy with fusion imaging, the co-registration of MRI scans with real-time ultrasound guidance.
As with the company's Ablatherm platform the system utilizes robotic assistance.
The Focal One platform also features a new level of HIFU technology with dynamic focusing that allows changes to the focal point of high energy to target specific prostate lesions.
The current HIFU approach used on Edap's Ablatherm platform delivers a static focus, directing energy for a hemi-gland ablation of a large lesion.
"Focal One can target smaller lesions on either the posterior side or on the anterior side of the prostate, and there is no need to wait between two HIFU deliveries, therefore the procedures can go faster," said Oczachowski.
Focal One is approved for sale in Europe where CEO Oczachowski estimated half of prostate treatments utilize the new platform.
"In Europe, Focal One is opening markets for Edap Hospitals that have been surgically oriented are getting into HIFU because of the dynamic focal strategy for treatment. It becomes a compliment to their surgical strategies," he said.
He added that 95 percent of prostate cancer ablations using HIFU in Europe are performed on Edap systems, the remainder with the company's only competitor for this indication, Sonacare Medical LLC based in Charlotte, N.C., which Oczachowski said is primarily focused on the U.S. market.
According to the Focused Ultrasound Foundation (FUC), manufacturers reported 61,749 prostate HIFU treatments in 2016, compared to 20,000 in 2014, representing 37 percent of HIFU treatments for any indication worldwide that year.
There are 46 commercial treatment sites for prostate in the U.S., compared to 180 such centers in Europe, according to the FUC.
In its 2016 report, the foundation credited Edap's Ablatherm platform with treatments for more than 45,000 patients at 300 sites worldwide, while the Sonablate HIFU from Sonacare was used to treat 15,000 patients.
The major barrier to wider adoption for HIFU prostate cancer therapy is reimbursement.
In July 2017, a new billing code took effect for HIFU ablation of prostate tissue with the Centers for Medicare and Medicaid Services (CMS).
This C-code covers whole gland prostate ablation, partial prostate ablation or whole and partial salvage ablation.
Yet it is only a partial step toward wider reimbursement as the code covers only the facility fees and does not cover other costs, significantly the fee for the urologist operator and the anesthesiologist.
Currently in the U.S., only private pay patients can afford the treatment that the FUC estimated to cost $25,000.
Edap CEO Oczachowski said expanded reimbursement in Europe is increasing patient volumes every year.
"France granted full reimbursement two years ago, greatly increasing the patient load. Germany has a DRG [diagnostic related group] code. Italy grants a nonspecific code, and we are hoping by the end of summer to have a new, specific code. In the United Kingdom the procedure is reimbursed if the technology is used as part of a clinical trial," he said.
In the U.S., he said the private pay market is a fraction of the wider market opportunity.
During a July 25 conference call with analysts, Edap offered a presentation from Dipen Parkeh, a practicing urologist who is the Chair of the Department of Urology at the University of Miami Miller School of Medicine.
Responding to questions about the potential patient response to full reimbursement for the procedure, Parkeh said, "I am not a marketing person. These are still early days, so I would not give a number. But as a practicing physician I can see the current volumes we have would easily double or triple if reimbursement is resolved."
"There is a huge demand from patients to get this focal treatment. With the approval for the C-code, I expect this demand will go up. I have patients with a non-aggressive cancer who are deferring treatment in the hope the HIFU treatment will soon be covered by their insurance."