U.S. FDA-approved DaxibotulinumtoxinA for Injection (DAXI) from Revance has been studied extensively for treatment of glabellar lines in recent years. To advance understanding of potential new applications, Plastic Surgery Practice sat down with Michael Kane, MD, FACS, to learn more about the usage of DAXI and its overall effects. Kane is an aesthetic surgeon who has been practicing in New York City for more than 30 years and operates a private practice on Manhattan’s Upper East Side where he performs a wide variety of cutting-edge cosmetic procedures, facial rejuvenation, and injections.
PSP: When were you introduced to DAXI and how are you using it?
Kane: I have been a consultant to Revance for over 17 years, and an advisor, investigator, data analyst, protocol writer, and speaker for Revance during my time there. I have been working with DAXI since it was first created by one of the company’s founders, Jacob Waugh, MD.
As there’s a bit of turnover in the pharmaceutical industry, I’ve been working with DAXI longer than anyone. Then and now, the company’s focus was on developing a broad spectrum of aesthetic and therapeutic indications for DAXI (brand name DAXXIFY), including facial wrinkles, such as glabellar lines, and muscle movement disorders, such as cervical dystonia.
PSP: How has your use of DAXI evolved over time?
Kane: I began using DAXXIFY shortly after its approval for glabellar lines in September 2022. It was an easy formulation to integrate into my practice. Initially, I was a bit cautious with my use of DAXXIFY, as I am with any new product, and injected several patients on-label fashion as no botulinum formulations are identical, and DAXXIFY is powered by its proprietary peptide. Now, I use it at different doses in different muscle groups of the face in an off-label fashion as I would use any botulinum formulation. Perhaps most importantly, my patients are highly satisfied with their results.
PSP: How exactly does DAXI treat forehead lines?
Kane: While DAXXIFY is currently only FDA-approved for the treatment of moderate-to-severe frown lines, the product’s mechanism is essentially the same for treating forehead lines (FHL).
DAXXIFY is the first and only injectable neuromodulator powered by Peptide Exchange Technology一a formulation free of human serum albumin or animal-based components. How it works is that neuromodulators temporarily weaken the facial muscles that cause wrinkles. DAXXIFY is administered via injection by a licensed aesthetics healthcare provider, typically using a 30-to-33-gauge sterile needle. DAXXIFY contains a peptide to stabilize the active ingredient, instead of human or animal byproducts used in conventional frown line treatments. Based on data from the SAKURA Phase 3 clinical trial program, DAXXIFY was well tolerated and achieved clinically significant improvement in glabellar lines with long-lasting results and high patient satisfaction.
PSP: Can you tell me how the study was conducted and explain your research findings?
Kane: Two Phase 2a open-label studies were performed to evaluate DaxibotulinumtoxinA for dynamic forehead lines (FHL). The protocol was designed to analyze efficacy, dose response, and safety of DAXI for injection in treating FHL. The study objective was to report on the efficacy, duration, and safety of DAXI for a range of FHL doses.
In the dose-escalation study, doses of DAXI ranging from 12U to 30U were administered to FHL 2 weeks after each subject (N=81) received 40U of DAXI injection of the glabellar lines. Primary endpoint was measured at week 6 (4 weeks after FHL treatment), and patients were followed every 4 weeks until return to baseline.
In the single-arm study, subjects (N=48) received a single administration of 32U of DAXI for FHL in combination with 40U for GL and 48U for LCL. Primary endpoint was measured at week 4, and patient visits occurred every 4 weeks until return to baseline. Integrated research results at 4 weeks after FHL treatment indicated that the proportion of patients with investigator rated FHL severity of none was lowest with 12U and highest with 30U and 32U.
These are results that I think anyone would have expected. However, what was striking about this dataset was the break in duration tied to dose. In particular, median time to loss of none or mild FHL on both investigator and patient assessment for all responders was 20 weeks for 18U, 24U, 30U, and 32U doses.
With DAXI doses of 18U and above, there was a graded efficacy response without loss of duration or graded duration response with dose. For patients with moderate or severe FHL, DAXI 18U and 24U were the lowest doses that balanced duration of effect with the ability to preserve some forehead movement. All doses were well tolerated, with no dose-response observed for any adverse event. No brow ptosis was reported.
I think the most difficult area of the face to properly dose is the forehead. Frequently low doses are used there to preserve animation and prevent brow ptosis. However, these lower doses typically would not last as long as higher doses. Daxxify has broken the dose-duration effect commonly seen in the forehead and allows one to titrate motion from 18 to 32 units without sacrificing duration.
PSP: What factors are assessed when determining dosing?
Kane: When treating dynamic forehead lines, dose selection must balance wrinkle severity with the patient’s desired degree of movement and expression. Like many toxin treatments, the ideal FHL dose will differ by patient, depending upon patient demographics, characteristics, muscle mass, brow position, and desired aesthetic outcome. In almost all cases, patients today want natural-looking results.
PSP: What is the efficacy, duration, and safety of DAXI?
Kane: DAXXIFY has the ability to deliver yearlong results with as few as two treatments and has been proven to be highly effective, generally safe, and well tolerated. Approved label includes the full 36-week data demonstrating a long-lasting treatment effect based on the pivotal Phase 3 SAKURA clinical program, which included more than 2,700 patients and approximately 4,200 treatments. DAXXIFY achieved clinically significant improvement in glabellar lines with long-lasting results and high patient satisfaction, notably a median duration of 6 months and up to 9 months for some patients. Also, results can be seen as early as day one after treatment and typically seen within 2 days.
PSP: Who is the ideal candidate for DAXI?
Kane: DAXXIFY is indicated for the temporary improvement of moderate-to-severe frown lines (glabellar lines) in adults. It can be used on all adult patient types, and the clinical studies supporting DAXXIFY included a wide range of patient types, such as gender and age.