The FDA has doled out two manufacturing-related complete response letters (CRLs), slamming the brakes on prospective therapies from AbbVie and Grace Therapeutics.
For AbbVie, the Chicago drugmaker had been looking to bolster its industry-leading aesthetics portfolio with a fast-acting follow-on to its blockbuster Botox franchise in trenibotulinumtoxinE (TrenibotE). TrenibotE is a first-in-class botulinum neurotoxin serotype E that could comprise a new option for those looking to treat moderate to severe glabellar lines with a short duration of aesthetic effect.
AbbVie's experimental injection is meant to last two to three weeks versus the standard months-long duration of effect with Botox.
However, the FDA has now requested more information on AbbVie’s manufacturing processes for the product, the company said Thursday. The CRL doesn’t flag any safety or efficacy concerns or request additional clinical data, with AbbVie maintaining confidence that it can address the agency’s comments “promptly” with a “thorough response” in the coming months.
"We strongly believe trenibotulinumtoxinE is an important innovation in botulinum toxin science, with the potential to expand options for patients interested in facial aesthetics," AbbVie’s chief scientific officer and EVP of R&D, Roopal Thakkar, M.D., commented in a company release. "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."
The company’s head of aesthetics R&D, Darin Messina, Ph.D., previously said that the product “has the potential to transform the aesthetic toxin treatment landscape for new patients,” as it allows prospective users to experience a quick “trial” use of Botox before going for the longer-lasting version. The injection takes effect as soon as eight hours after administration, whereas standard Botox takes a few days to set in.
A new addition to AbbVie’s Botox portfolio could help boost declining sales, with the company's cosmetic Botox revenues slipping 4.3% in 2025. The company made $4.86 billion in global aesthetics sales last year, a 6.1% decline from 2024, of which $2.6 billion came from Botox in its cosmetic uses.
The drug franchise is also indicated for several therapeutic uses, including chronic migraines and overactive bladder, from which it collected $3.7 billion in separately reported sales last year.
Botox has been a go-to aesthetic treatment since its 2002 approval for its first cosmetic use, with AbbVie taking ownership through its 2020 acquisition of Allergan. The drug is a plasma-derived product that AbbVie has recently been looking to defend against Inflation Reduction Act (IRA) price reductions, citing the IRA’s purported exclusion of plasma drugs from pricing controls.
Rejection for Grace Therapeutics
AbbVie wasn’t the only drugmaker to receive bad news from the FDA this week.
In a separate action, the agency rejected Grace Therapeutics’ injectable form of nimodipine in aneurysmal subarachnoid hemorrhage (aSAH). The asset is coded as GTx-104.
The FDA's qualms came down to the non-clinical section of Grace’s drug application, the company said. Specifically, the FDA cited issues with leachables data for product packaging, as well as non-clinical toxicology risk assessments and “product manufacturing deficiencies” at Grace’s contract manufacturing organization.
Still, the company is “confident in the robust data package” that supports its submission and believes that the issues can be addressed in a resubmission, CEO Prashant Kohli said. Grace will now request a Type A meeting with the agency to discuss next steps for a potential path forward.
Nimodipine has been used to treat patients with subarachnoid hemorrhage since 1988, when it was first introduced as a capsule. In 2013, an oral solution of the drug hit the market to help reduce hospital administration errors that had caused patient deaths in the past.
Grace’s version uses a “unique nanoparticle technology” that supports a water-based formulation of an insoluble drug product for a standard IV infusion, potentially eliminating the need for nasogastric tube administration in patients who are unconscious or otherwise can’t swallow, according to the company.
In a study of patients hospitalized with aSAH, those who received Grace’s GTx-104 charted a 19% reduction in at least one incidence of clinically significant hypotension compared to those who were given oral nimodipine. Grace’s therapy was also supported by additional observed benefits, including fewer ICU readmissions and ventilator days, plus a greater percentage of patients who had favorable functional outcomes at 90 days after receiving the drug.
There were eight deaths within the GTx-104 arm of the trial, but all deaths across the study were attributed to the severity of the patient’s underlying disease, Grace said. The condition is caused by a ruptured brain aneurysm, which causes bleeding in the subarachnoid space between the brain and the skull and can lead to aSAH, an uncommon type of stroke with a high mortality rate.