FDA Issues Complete Response Letter for Zolmitriptan
Zosano plans to request a Type A meeting with the FDA to discuss strategies to address the FDA’s comments regarding the new drug application.
Steven Lo
Zosano Pharma announced that it has received a complete response letter (CRL) from the FDA for its zolmitriptan transdermal microneedle system (Qtrypta) in correlation with the new drug application (NDA) it had submitted.1
Inconsistent zolmitriptan exposure levels observed across clinical pharmacology studies which had been previously identified in the FDA’s discipline review letter (DRL) in September, were among the main reasons cited for the CRL.
The CRL also noted differences in the exposure levels of zolmitriptan observed between subjects who received different lots of the drug in the company’s trials as well as inadequate pharmacokinetic bridging between the lots that made the interpretation of some safety data unclear.
“We are working diligently to address the deficiencies identified by the FDA and look forward to the possibility of resubmitting our NDA,” said Steven Lo, president and chief executive officer, Zosano, in a statement.
Zolmitriptan, a treatment for acute migraine also known as its adhesive dermally applied microarray (ADAM) platform, had its NDA accepted by the FDA in March 2020 with an original Prescription Drug User Fee Act (PDUFA) action date of October 20, 2020, which since then has been rescheduled.2
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High plasma concentrations of zolmitriptan unexpectedly observed in 5 study subjects enrolled in the company’s pharmacokinetic studies were also among the reasons cited for the CRL. As a result, the FDA recommended that Zosano conduct a repeat bioequivalence study between 3 of the lots used during development.
Additional product quality validation data, which were planned to be submitted following approval, if received, was noted within the CRL as a requirement if the company planned to submit an application. Additionally, the CRL mentioned that inspections of Zosano’s contract manufacturing facilities were not able to be conducted due to the US government and/or agency-wide restrictions on travel but would be required before the application may be approved.
Zosano also noted that it plans on requesting a Type A meeting with the FDA to discuss strategies to address the comments in the CRL. Lo stated, “We expect that the Type A meeting with the FDA will provide clarity on the next steps for the program, which we will communicate once solidified. There are thousands of people suffering from migraine attacks that are not adequately addressed with available drugs, and we continue to believe that Qtrypta, if approved, could offer a much-needed new therapy for these patients.”
In June 2020, new post-hoc efficiency analyses of the adhesive dermally applied microarray (ADAM) zolmitriptan from its open-label, long-term study were presented virtually at the 2020 American Headache Society (AHS) Annual Meeting, which suggest that the results were consistent with what was previously observed in the phase 2/3 study results.3
The data suggested that across all 6 efficacy measurements—pain freedom at 2 hours, pain relief at 2 hours, sustained pain freedom for 2 to 24 hours, sustained pain freedom for 2 to 48 hours, sustained pain relief for 2 to 24 hours, and sustained pain relief for 2 to 48 hours—the migraine headaches treated with 3.8-mg ADAM zolmitriptan displayed meaningful clinical improvements compared to those treated with placebo.
