Event – EnteroMedics puts earlier endpoint miss behind it as it heads for panel
After a number of snags, including a scheduling conflict, EnteroMedics is finally getting its chance to convince the FDA of the merits of its antiobesity neurostimulation therapy. Armed with updated trial data that improve on an earlier time point, the company will go before the Gastroenterology & Urology Devices Panel on June 17.
The meeting, initially planned for May 29, will focus on 18-month data from the ReCharge trial of EnteroMedics’ Maestro device, which sends electrical impulses to the vagus nerve to ease sensations of hunger. ReCharge missed its primary endpoint when its one-year results read out, but apparently an extra six months’ use of the device makes all the difference.
12-month data from the trial, reported early last year, showed that Maestro caused patients to lose an average 24.4% of their excess weight, compared with 15.9% for patients who had undergone implantation of a sham device. The difference between the two groups did hit statistical significance, but ReCharge’s protocol called for Maestro to demonstrate an improvement of 10 percentage points, so technically the study failed (Trial miss gives EnteroMedics a jolt, but approval push continues, February 11, 2013).
Results at 18 months paint a different picture – but one that is still not wholly convincing. Patients in the Maestro group dropped 25% of their excess body weight on average, compared with an average 12% loss among the control patients. Statistical significance, as well as that elusive 10 point minimum difference, were reached.
However, they were not reached thanks to an improved performance of Maestro but to a relapse among the sham patients. And, according to clinicaltrials.gov, the ReCharge protocol specifies the 12-month measure as the primary endpoint anyway.
EnteroMedics could perhaps make one of two cases: that either the panel should be guided by the 18-month results rather than the earlier data, or that the 10-point “super-superiority” was not necessary in the first place.
And while the efficacy difference has improved – although Maestro’s efficacy itself has barely changed – in the longer term, safety has worsened. At 12 months Maestro’s rate of device-related serious adverse events was 3.1%, which at the time the company touted as a win as it was lower than the protocol-specified endpoint of 15%. At 18 months the serious adverse events rate had increased to 4.3%, though this was still significantly lower than the threshold.
For comparison, the complication rates for laparoscopic gastric bands, sleeve gastrectomy and Roux en-Y gastric bypass are 6%, 18% and 24% respectively. But these can result in far greater weight loss; bypass surgery patients lose around 70% of their excess body weight, nearly three times as much as with Maestro.
EnteroMedics must hope that it can persuade the panel, and after that the agency. Maestro is its only product, and its current cash pile will be unlikely to last it a year. If Maestro is approved, it will bring the company $287m in 2020, according to EvaluateMedTech’s consensus forecasts.
Analysts from Canaccord Genuity put the implant’s chance of gaining FDA approval at better than fifty-fifty – hardly enthusiastic. Its chances of a positive panel vote are much the same.