The FDA has issued two manufacturing-related Complete Response Letters (CRLs), putting the brakes on promising treatments from AbbVie and Grace Therapeutics.
Chicago drug company AbbVie was looking to strengthen its industry-leading beauty product portfolio with Trenibotulinumtoxin E (TrenibotE), a fast-acting follow-up to its blockbuster Botox franchise. TrenibotE is a first-in-class botulinum neurotoxin serotype E and may represent a new option for those looking to treat moderate to severe glabellar wrinkles with short-term aesthetic results.
AbbVie’s experimental injection is expected to last two to three weeks, compared to Botox’s standard duration of several months.
However, the FDA is now requesting more information about AbbVie’s manufacturing process for its products, the company announced Thursday. The CRL did not raise safety or efficacy concerns or request additional clinical data, and AbbVie is confident it will address the agency’s comments “quickly” and with a “thorough response” in the coming months.
“We strongly believe that TrenibotulinumtoxinE is an important innovation in botulinum toxin science and has the potential to expand options for patients concerned about facial aesthetics,” Roopal Thakkar, MD, AbbVie’s chief scientific officer and vice president of research and development, commented in a company release. “While disappointing, we remain confident in the strength and integrity of the application and are poised to respond quickly to agency feedback to support the completion of the review.”
Dr. Darin Messina, the company’s head of cosmetic research and development, previously said the product “could change the landscape of cosmetic toxin treatment for new patients” by allowing prospective users to experience a brief “trial” use of Botox before moving on to a long-lasting version. Standard Botox takes several days to take effect, but the injections take effect within eight hours after administration.
New additions to AbbVie’s Botox portfolio could boost sales declines, as the company’s cosmetic Botox sales are set to decline 4.3% in 2025. The company’s global beauty sales were $4.86 billion last year, down 6.1% from 2024, of which $2.6 billion came from Botox in cosmetic applications.
The drug franchise, which also has several therapeutic uses such as chronic migraine and overactive bladder, had separately reported sales of $3.7 billion last year.
Botox has been a go-to beauty treatment since it was first approved for cosmetic use in 2002, and AbbVie took ownership with its acquisition of Allergan in 2020. The drug is a plasma-derived product, and AbbVie recently sought to fight price cuts under the Inflation Control Act (IRA) because the IRA allegedly excludes plasma-derived products from price controls.
Grace Therapeutics Rejection
AbbVie wasn’t the only drug maker to receive bad news from the FDA this week.
In a separate lawsuit, authorities denied Grace Therapeutics’ injection of nimodipine for aneurysmal subarachnoid hemorrhage (aSAH). This asset is coded as GTx-104.
The company said the FDA’s concerns came down to the non-clinical portion of Grace’s drug application. Specifically, the FDA cited issues with leachable data on product packaging, non-clinical toxicity risk assessments, and “product manufacturing deficiencies” in Grace’s contract manufacturing organization.
Still, the company is “confident in the robust data package” supporting its submission and believes the issue can be resolved with a resubmission, CEO Prashant Kohli said. Grace will now request a Type A meeting with the authorities to discuss next steps regarding possible future directions.
Nimodipine has been used to treat patients with subarachnoid hemorrhage since it was first introduced in capsule form in 1988. In 2013, an oral solution of the drug entered the market to reduce mismanagement in hospitals that had caused patient deaths in the past.
The company said Grace’s version uses “proprietary nanoparticle technology” that supports water-based formulations of insoluble drugs for standard intravenous infusions, potentially eliminating the need for nasogastric tube administration for patients who are unconscious or unable to swallow.
A study of patients hospitalized with aSAH showed that patients who received Grace’s GTx-104 had a 19% reduction in the incidence of at least one clinically significant hypotension compared to patients who received oral nimodipine. Grace’s treatment was also supported by additional observed benefits, including reductions in ICU readmissions and ventilator days, as well as an increase in the proportion of patients with good functional outcomes 90 days after drug administration.
Although there were eight deaths in the GTx-104 trial arm, all deaths in the study overall were due to the severity of the patients’ underlying conditions, Grace said. This condition is caused by the rupture of a brain aneurysm, which causes bleeding in the subarachnoid space between the brain and skull, which can lead to aSAH, a rare type of stroke with a high mortality rate.
