Following CRL, Revance says it's clear on instructions for resubmitting BLA
In October, the FDA handed Revance Therapeutics a CRL for its botox-based frown line therapy, and the company said that the deficiencies stemmed from a manufacturing site. Now, the company says it has received the Type A meeting minutes, and clear instructions for addressing the shortcomings.
Revance must produce three consecutive drug substance lots and one drug product lot for DaxibotulinumtoxinA for Injection for glabellar lines, in order to resubmit its BLA, the company said. This was determined in a Dec 15 meeting. Another inspection of the manufacturing site in northern California will be required after the resubmission. The FDA has up to six months to complete the inspection and review.
“We believe we have a clear path to resubmission of the BLA for DaxibotulinumtoxinA for Injection for glabellar lines following our Type A meeting with the FDA,” CEO Mark Foley said in a statement. “As we have noted previously and as confirmed by the FDA during the meeting, the CRL was related to the onsite inspection of our manufacturing facility and not the safety and efficacy of our drug product. The qualification of our new WCB is in progress and we look forward to resubmitting the BLA as soon as possible.”
Regulators found the Revance cell banks testing methods — which are done to ensure the safety and purification of a product — were not sufficient enough to track quality, and the manufacturing process was different from the one originally proposed for commercialization, according to a Form 483. Procedures also lacked written details, and the actual yield and theoretical yield didn’t match up, the FDA said.
The BLA was originally submitted in January 2020, but a review was delayed because of the Covid-19 pandemic.
There were no other issues raised with the drug, the biotech said. But investors reacted, as shares plummeted more than 30% after the closing bell. That fall has stopped, but not recovered yet, as shares of $RVNC were still $14.31 shortly after the opening bell.
Though the trials did not study the product against brand-name Botox, the best-selling Allergan product generally lasts for three to four months. Pivotal Phase III studies showed the treatment, dubbed DaxibotulinumtoxinA for Injection, allowed adults to maintain mild frown lines for a median of 24 weeks with no serious side effects. Allergan’s brand-name Botox is said to last between three and four months.
Even before the CRL, Revance had problems with the FDA, thanks to, in part, a backlog on inspections. The FDA said in November 2020 that it’s “actively working to define an approach for outstanding inspections,” but was held up due to travel restrictions. That’s a problem that hasn’t yet gone away, thanks to the emergence of the Omicron variant.
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