CEO: Dr. Harith Rajagopalan
Based: Waltham, MA
The scoop: Fractyl's technology stems from the long-standing observation that when bariatric surgery patients that have a procedure where the duodenum, the first part of the intestine that absorbs nutrients, is either blocked or bypassed they demonstrate almost immediate improvement in glycemic control--even before any weight is lost. The startup has developed a duodenal mucosal resurfacing device using thermal ablation, the Revita DMR System, which offers improvement in glycemic control for Type 2 diabetics with a relatively painless, endoscopic procedure that can be performed in a clinic setting.
What makes Fractyl Fierce: The startup has shown in proof-of-concept data that patients achieved a significant drop in hemoglobin A1C levels (HbA1c) by three months after the procedure with a maintenance of those results at six months.
The trial was in 39 patients on one oral medication with uncontrolled diabetes who had an average HbA1c level of 9.5%. After 6 months, the 28 patients who had received DMR over several centimeters of duodenum dropped to an average of 7.1% HbA1c from their mean of 8.5%. They also lost an average of 2.3 kg in weight, but the weight loss benefit did not correspond with the size of the HbA1c reduction. The patients that received the treatment over a shorter segment of their duodenum did not experience as great a benefit.
To put those results a bit more in context, a normal HbA1c level is about 4.5% to 6%, according to the Mayo Clinic. In an uncontrolled diabetic, that measurement might be above 8%. An HbA1c level between 5.7% and 6.4% in considered prediabetes. A typical treatment target for a diagnosed diabetic is about 7% or less.
So, the decline achieved in that early testing could be enough to push an uncontrolled diabetic close to a typical treatment target. The procedure is currently in a major European trial that will remain single-arm through the first quarter and then transition to a randomized study.
The ongoing trial starts with 50 patients across 10 sites; it will then expand to up to 240 patients in a double-blinded, sham-controlled trial that will start in the second quarter. The primary endpoint is HbA1c change in uncontrolled Type 2 diabetics--with that defined as patients on an oral medication with an HbA1c level of 7.5% to 10%.
Fractyl nabbed a $40 million Series C round in September 2014 to support the trial. The company expects the results will be sufficient to support a CE mark during 2016, although it's just starting conversations with the FDA, so a pivotal U.S. trial seems likely to be a ways off.
Type II diabetics typically progress from treatment with diet and exercise to an oral medication, usually metformin. Next is the progression to two or three oral drugs, finally followed by injectables such as insulin. But at all stages of therapy--roughly half of diabetic patients remain poorly controlled.
Remaining uncontrolled contributes to the emergence of comorbidities that can lead to kidney failure, blindness and amputation. These complications account for much of the quality of life impairments and healthcare costs associated with Type II diabetes.
Rather than resorting to bariatric surgery, with its weeks of recovery time and high costs, the ReVita procedure could end up being simple and painless enough to perform in a clinic.
"The patient would come into the endoscopy suite and would be placed under anesthesia such as propofol," described Fractyl co-founder and CEO Harith Rajagopalan in an interview with FierceMedicalDevices. "Endoscope and catheters are inserted and the procedure of ablating would be performed. Then the patient wakes and goes into recovery. It takes about an hour--with iterative improvements to the device we think we can get to less than that."
He said that thus far clinical trial patients have been admitted overnight as a precaution. But two-thirds haven't reported any discomfort, while the remainder only report a mild discomfort that can be treated effectively with acetaminophen. The ultimate physician target for the procedure is an endoscopist.
What to look for: More clinical data. Fractyl has already released positive proof-of-concept data, but now it's ready for a bigger study. The company is currently in the midst of a large European and South American trial, so look for data from that study. The second phase of that sham-controlled trial is slated to start in the second quarter next year and enroll up to 240 patients. Also, watch for signs of progress toward getting a U.S. pivotal trial underway. If it can get beyond regulatory trials, next Fractyl will likely need to demonstrate its value to payers with outcomes studies.
-- Stacy Lawrence (email | Twitter)
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