When the U.S. Food and Drug Administration last month raised concerns with Zosano Pharma’s marketing application for its acute migraine patch, the company concluded it wouldn’t meet its Oct. 20 goal for approval. Earlier this week, Zosano got the approval decision it expected—though not the one it had hoped for.
The FDA slapped Zosano with a complete response letter for its migraine drug-device combo Qtrypta, the company said. It’s now on the hook to deliver new bioequivalence data, and it plans to meet with the FDA to sort out concerns over drug exposure levels in a pharmacokinetic study.
Qtrypta is an intracutaneous patch—about the size of a quarter—that uses drug-coated microneedles to deliver the well-established migraine med zolmitriptan to the bloodstream. The aim is to provide faster absorption than a pill, which means swifter relief from migraine pain, Zosano CEO and President Steven Lo said in an interview.
The FDA’s letter didn’t relate to issues with the patch itself, Lo explained. Instead, the agency flagged inconsistent zolmitriptan exposure levels across clinical pharmacology studies, linked to patients who received different lots of Qtrypta in Zosano's trials. It also cited subpar pharmacokinetic bridging between lots of the drug, which hampered interpretation of safety data.
Specifically, the FDA rejection outlined unexpectedly high plasma concentrations of zolmitriptan in five volunteers from a pharmacokinetic study, urging Zosano to run a repeat bioequivalence study on the three lots of Qtrypta used in testing. The FDA’s letter covered data on 774 patients dosed with Zosano’s patch across five trials.
The company had also planned to submit additional quality product validation data after Qtrypta’s approval, but it will now have to submit those along with its next application.
One other hurdle? The FDA still needs to inspect Zosano’s contract manufacturing facilities, though it’s currently unable to do so amid COVID-19 travel restrictions, Lo said. It’s unclear when the FDA plans to visit those sites—spread across California, North Carolina, Alabama and France—but completion of the inspections is now mandatory for Qtrypta to grab a green light.
As for next steps, the company is confident it can address the FDA’s concerns.
The higher drug exposure levels arose in pharmacokinetic studies, rather than safety or efficacy trials, during which side effects were generally mild, Lo said. Meanwhile, the higher exposure levels flagged in those five patients didn’t trigger any health scares, either.
The company will request a Type A meeting with the FDA to hash out next steps and get a handle on the agency’s concerns. At that meeting, Zosano will need to submit a briefing document on Qtrypta, and, to that end, it’s enlisted the aid of additional pharmacokinetic and pharmacology experts to get things sorted, Lo said.
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Zosano has had a few weeks to prepare for this outcome. In late September, the company received a discipline review letter from the FDA citing problems with the same five patients who displayed high plasma levels of zolmitriptan. While the company had originally hoped to snare approval for its drug-device combo by Oct. 20, the agency's September communication prompted Zosano to dial back those expectations.
Once the company meets with the FDA, it will have a better sense of when Qtrypta might be back in the running, but Zosano plans to “persevere," Lo said, adding that the company "believes the drug will still be an option for migraine patients should it get approved.”
If Qtrypta grabs an approval, it will enter a migraine field that's grown crowded in recent months thanks to approvals for Biohaven’s Nurtec ODT, AbbVie’s Ubrelvy and Eli Lilly’s Reyvow. Meanwhile, the company is pursuing a follow-up Qtrypta indication for cluster headache, currently in phase 2/3. It’s a smaller patient pool, but one where current treatment options are scarce, Lo noted.
Zosano’s microneedle patch could eventually tee up easier vaccine delivery, too, since the drug-device combo is manufactured and delivered in a way that bypasses the need for cold chain storage, Lo said.