FDA Issues Complete Response Letter for AbbVie’s Rapid-Onset Neurotoxin, TrenibotulinumtoxinE

AbbVie and Allergan Aesthetics have announced that the US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the Biologics License Application for TrenibotulinumtoxinE (TrenibotE), an investigational botulinum neurotoxin serotype E under review for the treatment of moderate to severe glabellar lines.¹ While the CRL delays potential approval, the company emphasized that the agency’s feedback was limited to manufacturing-related issues and did not cite concerns regarding safety or efficacy, nor did it request additional clinical trials.

“We strongly believe trenibotulinumtoxinE is an important innovation in botulinum toxin science, with the potential to expand options for patients interested in facial aesthetics," said Roopal Thakkar, MD, Executive Vice President of Research and Development and Chief Scientific Officer at AbbVie. "Though disappointed, we remain confident in the strength and integrity of our application, and we are well positioned to respond to the agency's feedback promptly to support completion of the review."¹

The regulatory update is notable given the interest surrounding TrenibotE as a potential first-in-class neurotoxin distinguished by both rapid onset and short duration of action—features that could offer a differentiated option within the evolving facial aesthetics landscape. According to AbbVie, the company expects to respond to the FDA’s manufacturing-related comments in the coming months and remains confident in the strength of its submission. Regulatory reviews for TrenibotE in other countries are ongoing and progressing as expected.

A Differentiated Profile: Rapid Onset and Short Duration

The company submitted a Biologics License Application (BLA) to the FDA in April 2025.² The submission was backed by a robust clinical development program involving more than 2,100 patients and included data from 2 pivotal phase 3 trials, M21-500 and M21-508, as well as a long-term, open-label safety study, M21-509.

TrenibotE has attracted attention for its distinct pharmacologic profile. As a botulinum toxin serotype E, it differs from currently marketed serotype A neurotoxins in both onset and duration. The clinical data suggests treatment effects may begin as early as 8 hours after administration and last approximately 2 to 3 weeks. This contrasts with currently available neurotoxins, which typically have a slower onset and longer duration.

TrenibotE may be especially well suited for toxin-naïve or hesitant patients who are unsure about committing to longer-lasting neuromodulation. Its “try-before-you-buy” nature may help overcome aesthetic anxiety regarding appearance changes or treatment value, potentially expanding the patient base for neurotoxin therapies.

"Are we going to have ones that maybe last longer? Are we going to have different products in the market? Will that move the price? Will this become just something that everyone does, kind of like getting your hair done? It’s just really an exciting field to be in,” Rosalyn George, MD, founder of Wilmington Dermatology Center in Wilmington, North Carolina, and investigator in several TrenibotE studies, said in a recent interview with Dermatology Times.

Latest Data from AAD 2026

Further data was shared at the recent 2026 American Academy of Dermatology (AAD) Annual Meeting.³ Clinical improvements were observed as early as 48 hours after administration, with a substantial proportion of patients achieving ≥1- and ≥2-grade improvements in FWS scores, even with repeated doses over time. Safety outcomes were favorable and remained consistent across treatment cycles. The most commonly reported treatment-related adverse events included headache, injection site pain, and bruising.

“Robust research has been done in the trenibtoulunumE program, including this latest open-label phase 3 study using the first Type E botulinum toxin. Safety and efficacy were clearly demonstrated after 3 sequential doses of Trenibotulinum toxin. Trenibotulinum toxin’s unique profile of early onset as fast as 8 hours with duration of only 2 to 3 weeks may give those patients considering botulinum toxin treatment a trial option,” trial investigator and director of Skin Associates of South Florida and the Skin Research Institute, Joely Kaufman, MD, told Dermatology Times.

References

1. AbbVie Provides Update on TrenibotulinumtoxinE (TrenibotE) Biologics License Application in the U.S. News release. AbbVie. April 23, 2026. Accessed April 24, 2026. https://news.abbvie.com/2026-04-23-AbbVie-Provides-Update-on-TrenibotulinumtoxinE-TrenibotE-Biologics-License-Application-in-the-U-S

2. AbbVie submits Biologics License Application to US FDA for trenibotulinumtoxinE (TrenibotE) for the treatment of glabellar lines. News release. AbbVie. April 24, 2025. Accessed April 24, 2026. https://news.abbvie.com/2025-04-24-AbbVie-Submits-Biologics-License-Application-to-U-S-FDA-for-TrenibotulinumtoxinE-TrenibotE-for-the-Treatment-of-Glabellar-Lines

3. Kaufman J, Coleman W, Gold M, et al. Safety and Efficacy of TrenibotulinumtoxinE Following Repeat Treatments for Glabellar Lines: Findings From an Open-Label Phase 3 Study. Poster presented at the 2026 American Academy of Dermatology Annual Meeting. Denver, Colorado. March 27-31, 2026.