For the acute management of migraine, a complete response letter (CRL) has been issued by FDA regarding the NDA for zolmitriptan (a selective 5-HT1B/1D receptor agonist) transdermal microneedle, as per notification published on 21 October 2020.

Zolmitriptan is delivered utilizing the Adhesive Dermally-Applied Microarray (ADAM) technology consisting of a drug-coated microneedle patch. The drug-coated microneedles diffuse into the dermis and epidermis where the drug dissolves and finally enters into the bloodstream. The NDA included data from five clinical trials, including the phase II/III ZOTRIP study that investigated the safety and efficacy of zolmitriptan in 333 patients for combating migraine.

In the CRL, the FDA observed inconsistent exposure levels of the zolmitriptan witnessed across the clinical pharmacology analysis. Furthermore, the FDA cited variations in zolmitriptan exposures between participants receiving different lots of zolmitriptan in the company’s studies and insufficient pharmacokinetic bridging between the lots that made elucidation of some safety data uncertain.

In five participants recruited in the pharmacokinetics studies, high plasma concentrations of zolmitriptan were witnessed. To combat these issues, the agency suggested that a repeat bioequivalence study be carried out between three of the lots utilized during the development.

Further product quality validation data, as well as an examination of the manufacturing facilities, would be needed before the resubmission of the NDA. It is anticipated that the type A meeting with the FDA will yield clarification on the subsequent steps for the program, which will be communicated once solidified.