While ersodetug missed the Phase 3 primary endpoint of a reduction in hypoglycemia events, Rezolute argued that this goal was confounded in part by behavioral factors. The FDA acknowledged the validity of this argument.
Two and a half months after its hypoglycemia drug failed a Phase 3 trial, Rezolute has aligned with the FDA on a potential path forward.
“It’s an unusual outcome,” Rezolute CEO Nevan Charles Elam told BioSpace, “to have this level of engagement with FDA.”
While ersodetug did not meet the primary endpoint of hypoglycemia events in the Phase 3 sunRIZE study in patients with congenital hyperinsulinism (HI), the California-based biotech was resolute in its conviction that the asset works. The “totality of the data” supports previous clinical evidence that ersodetug is active against hypoglycemia, Rezolute said in a January press release.
On that basis, the biotech stated its intentions to meet with the FDA in the first quarter of this year. That Type B meeting came to fruition earlier this month. On Tuesday, the company reported a positive outcome. At the time of this article’s publication, shares were worth $2.58, up around 7.5% since the markets opened.
On March 17, Rezolute presented the FDA with biomarker evidence of decreased insulin cell signaling in both treatment groups. The company also pointed to consistent improvements in time spent in hypoglycemia compared to placebo.
As for the missed endpoint, the unblinded nature of self-monitored blood glucose confounded the results, the company said. While allowing patients to report their own data is necessary for standard of care, the company explained in its press release, it “may have led to divergent behaviors between treatment groups during the study, which may have impacted the measurement of hypoglycemia.”
The FDA acknowledged the potential impact of “varied behavioral factors” on clinical trials in this heterogeneous patient population, according to Rezolute, including the associated limitations of measuring hypoglycemia via self-monitored blood glucose.
“We are extremely encouraged by the outcome of our meeting with FDA including the fact that, while acknowledging their feedback was preliminary, the agency did not dismiss sunRIZE outright on the basis of not meeting its primary endpoint,” Elam said in a statement.
The agency has encouraged Rezolute to submit study reports and analysis datasets, the company said, emphasizing its belief that this evaluation will determine whether there is sufficient evidence to support a New Drug Application for ersodetug.
Elam said the FDA’s request to do its own analysis of the data is “very, very unusual.”
“For a division to say ‘We’re going to do our own analysis, if you give us the data set, because we’re curious’… I haven’t seen that in years,” he told BioSpace.
The CEO’s positive feedback is a departure from recent highly publicized squabbles between the FDA and other biotechs, most notably this year uniQure over its investigational gene therapy for Huntington’s disease and Moderna regarding its mRNA-based flu vaccine.
These companies are not alone. Over the past year, myriad biopharma companies have noted a disconnect between guidance previously received from the FDA and regulatory feedback received alongside a PDUFA or pre-PDUFA decision. In addition to uniQure and Moderna, Biohaven, Replimune and Capricor Therapeutics have all been thrown for a loop by apparent FDA reversals.
Elam said that changes in glucose are clear, as opposed to a gene therapy or a biomarker like neurofilament light (NfL)—a key marker of neurodegeneration, reduced levels of which uniQure demonstrated with AMT-130.
“In some ways, it’s a little easier, because this is glucose, and if you can correct glucose values, they can usually be pronounced and demonstrable,” he said.
Elam was not the only person who lauded the Type B meeting.
“As an attendee of the meeting, I was extremely impressed observing FDA and Rezolute working together with a common understanding of the profound burden congenital hyperinsulinism places on patients and caregivers, and for their commitment to advance meaningful improvements in care,” Julie Raskin, CEO of Congenital Hyperinsulinism International, an international advocacy organization, said in a statement on Tuesday.
Ersodetug, a fully human monoclonal antibody in Phase 3 trials for HI and tumor hyperinsulinism, is the company’s only clinical-stage asset.
Elam acknowledged that following the FDA’s review of ersodetug’s trial data, the agency may still recommend that Rezolute conduct another randomized controlled trial. “But the fact that they’re digging in in this fashion is unusual, and I think . . . it’s because the clinical benefit we can all see.”
