Last year, we had projected that EDAP TMS (NASDAQ:EDAP) would report data from their Phase 2/3 trial(ENLIGHT) trial for the indication of low risk, localized prostate cancer. However, we have seen no statement on the results of the trial thus far. Ablatherm HIFU has been approved in the EU for quite some time, but their sales have never really taken off because of the lack of robust clinical data and shortcuts by the company.
On January 31st, 2013, the company reported that the pre-marketing approval(PMA) application for Ablatherm had been submitted to the FDA, yet still gave no indication on when results from the study should be expected. The PMA application was subsequently accepted by the FDA for filing on March 26, 2013. We would not expect a decision on the PMA until end of August at the very earliest and more likely Q4’13. FDA regulations provide 180 days to review the PMA and make a decision. In reality, the review time can stretch out significantly.
ENLIGHT was a multi-center US study comparing EDAP’s Ablatherm High Intensity Focused Ultrasound (HIFU) versus Cryotherapy. The primary endpoint is prostate-specific antigen (PSA) nadir < 0.5 ng/ml and stability of PSA, through 24 month follow up without a positive biopsy. Secondary endpoints include OS among others. The goal with this trial was to show that a simple outpatient procedure utilizing HIFU has similar efficacy to surgery, yet appears to have lower rates of some of the more troublesome side effects, like incontinence and impotence/erectile dysfunction. To date, there are no known randomised controlled trials evaluating HIFU[ref]. HIFU has generally shown good negative biopsy rates and high 5-year disease-free survival.
The side effect profile of a procedure matters greatly from a quality of life perspective, especially if these are low-grade cancers that don’t necessarily require immediate treatment. In prostate cancer, there is a lot of surveillance of their disease(PSA levels, symptoms,
or Gleason scores) that trigger treatment. Radical prostatectomy, external-beam radiotherapy, and brachytherapy are common in this setting for those with signs of disease progression. Overtreatment in prostate cancer has become quite a topic for debate due to the significant cost and side effects. Although they can provide high rates of disease control, they lead to impaired quality of life issues that most men will have to deal with for a substantial period.
We do have some problems/concerns with the study. First, they wrangled with the FDA for more than a decade on the endpoints/sizing for the study and enrollment was quite slow. Another problem is that cryotherapy is not standard of care in the US or EU. It’s mainly a highly localized treatment and it is less well established due to the lack of robust studies. Interest in cryoablation has probably diminished because of the high rates of erectile dysfunction, that are believe to be even higher than after radical prostatectomy. Additionally, for any biotech investor or trader, transparent disclosure of clinical data is the standard. The fact the company has chosen to not to be upfront with investors is troubling.
See this section below from their recent 20F(4/2) for a brief summary of their troubles.
In December 2001, our request for an additional Investigational Device Exemption (“IDE”) from the FDA to conduct clinical trials in the United States for the Ablatherm as a primary therapy was rejected. After redesigning the clinical protocol, we resumed the clinical trials in order to obtain FDA approval of the Ablatherm. In March 2009, facing patient enrollment issues on the cryoablation comparative arm of the U.S. ENLIGHT study, we met with the FDA to propose alternatives to the approved protocol. Following the December 11, 2009 panel[ref] experts recommendations and our discussions with the FDA, after thoroughly evaluating all options, in April 2010, we decided to discontinue enrollment of patients in the HIFU comparative arm of the study and completed the treatment of 134 patients in June 2010. The required two-year follow-up phase was completed in June 2012.
On January 31, 2013, we submitted our PMA to the FDA for our Ablatherm for treatment of low risk, localized prostate cancer. Our submission included data from the ENLIGHT U.S. Phase II/III clinical trial, as well as data from our extensive worldwide database of treatment information and follow-up data from patients who have undergone HIFU therapy for prostate cancer. On March 4, 2013, we received a positive administrative acceptance review notification from the FDA for our PMA application and on March 26, 2013 we received confirmation from the FDA that our PMA submission contained all of the information needed to proceed with the substantive review. Given the very challenging recommendations of the FDA with regards to our prospective study and its cryoablation comparative arm, there is a risk that the review of our submission may take longer than expected or may not meet the FDA’s requirements which could delay approval, if we receive it at all.
We are suspicious why the company has not released the topline results. It’s quite unusual for a company to hold onto such data for so long without revealing it. The following exchange from 3Q’12 conference call leaves us a bit puzzled and certainly colors our initial skepticism about their data. The FDA has little to do with the company presenting the data to investors or the medical community. Dodging this question warrants suspicion and CEO Marc Oczachowski sure says a lot without any meaning.
Jeffery Cohen – Ladenburg Thalmann & Co.
Okay, 80 machines and could you talk a little bit about, did you get back to the FDA and talk about your anticipated timeline if they – if the submission goes in the beginning of the year. What that might look like as far as our submission trial timeline, number of our anticipated patient’s outcomes and number of months to some results to be submitted?Marc Oczachowski – CEO
So, actually we – as I said, we expect to submit [outside] the FDA in the early days of January next year. Now, again in terms of publishing the clinical results we’re – we have no idea when we could do that and we won’t take and we won’t make any decision on that without the advice and the recommendation from the agency as we don’t want to interfere at all in their interpretation process of the clinical results of the trial.
HIFU has shown some promise[ref 1,2,3,4,5] in treating low-grade prostate cancers, so we don’t expect the trial to have “failed”, but there could be something about the data they don’t want to share. They will be at the AUA annual meetings in early-May, but their presentation does not have anything related to ENLIGHT. Instead there are several presentations related to data collected thru their patient database showing encouraging negative biopsy rates and actuarial biochemical disease free survival (BDFS) at 5 years with bladder outlet obstruction being the only notable side effect. It’s important they make the presentation and publication of the ENLIGHT data their #1 priority. So far, it has not been.
At December 31, 2012, cash and cash equivalents were 8.1M euros ($10.7M). For the full year 2012, revenue was approximately 26.1M euros (~$33.5M), up 16.9% year-over-year, largely in part to Sonolith sales. If they would like to turn HIFU device sales around, the ENLIGHT data will need to deliver and sign-on a fairly larger distributor/manufacturer like GE or Philips. Another quarter has come and gone without transparency on the ENLIGHT data[ref].
Disclosure: Author has no position.
