Revance presents 4 AAD VMX posters examining phase 3 study data for DAXI and the impact of HA filler manufacturing technologies on HA chain degradation.
Revance Therapeutics, an aesthetic biotechnology company, recently presented 4 abstracts highlighting the long-lasting effects of daxibotulinumtoxinA (DAXI) 3 months post treatment. The company presented the study data at the American Academy of Dermatology Virtual Meeting Experience (AAD VMX) 2021 in April.1
Three abstracts highlighted data from the phase 3 SAKURA-1 and SAKURA-2 trials (NCT03014622 and NCT03014635) of Revance’s investigational DAXI neurotoxin for injection to treat glabellar lines (GL).1-3
The findings included the elimination of GL with DAXI through a novel graphical representation of the entire distribution of GL severity ratings and changing scores used to depict patterns of efficacy over time.3
Pooled data revealed that 80% of participants treated with DAXI were rated as “none” at week 4, and 35% at week 12. Among patients rated “severe” at baseline, 68% and 24% were also rated as “none” at weeks 4 and 12, respectively. This represents a 3-point improvement from baseline, with 90% of all patients achieving a 2-point or greater improvement from baseline to week 4.1
“The concept of a longer-lasting form of neurotoxin has always been one that is the holy grail,” says Joel Schlessinger, MD, a dermatologist and cosmetic surgeon in Omaha, Nebraska, who was involved in the studies of both DAXI and RHA filler (TEOSYAL RHA 2; Teoxane Laboratories). “With these data, it does seem that therapeutic benefit lasts well into the third month and remains active in a significant amount of the population at week 12.”
The second poster included data from a subgroup analysis of the efficacy, duration, and safety of DAXI injections among adult women across multiple SAKURA age cohorts.2 The proportion of patients who achieved none or mild GL per investigator assessment at week 4 were 97.2% (18-45 years), 96.3% (> 45-55), 96.9% (> 55), and 96.7% (≥ 65).2
The third poster showcased results from an evaluation of how repeated DAXI use could affect the progression of static or resting GL.3
“DAXI-treated [participants] showed substantial and progressive improvement in static GL with repeated treatment,” write the study authors.3 “The extended duration of therapeutic benefit observed with DAXI in dynamic GL provides a longer window of muscle hypoactivity, permitting an extended period for dermal remodeling to occur. This can potentially account for the progressive improvement in static GL observed over repeated DAXI treatments.”
“There are many trials now that are aimed at optimizing neurotoxins to conceivably maximize the ability to approach 24 weeks, but DAXI was the first to even consider it,” Schlessinger notes. “They have laid down the gauntlet in this arena and it remains to be seen if they will come to market with a different package insert than other neurotoxins, but that would be a valuable marketing tool.”
Revance also presented a poster on the impact of hyaluronic acid (HA) filler manufacturing technologies on HA chain degradation.4
The authors examined soluble HA (sHA) fraction chain length, along with the distribution in commercial filler products.
“The concept of sHA is one that bears investigation,” Schlessinger says. “This area is… particularly of note given the concerns about reactions from COVID-19 and the vaccinations for COVID-19. Patients are looking for a longer-lasting product, so these types of studies further elaborate [on] the options available, while adding to the science behind fillers.”
Investigators used 13 US-marketed fillers from 5 manufacturing technologies and size exclusion chromatography (SEC) to examine the mean molecular weight of sHA released from the final formulation per syringe, and fragment sizes (< 30 kDa, < 100 kDa, and < 250 kDa).
“Preserved Network Technology (PNT) fillers released the longest sHA fragment chains (~ 500-600 kDa). Vycross fillers released the shortest sHA fragment chains (~ 100-165 kDa). PNT released the lowest amount of sHA compared to other technologies for all 3 low [molecular weight] fragment size categories, with 0% in the [less than] 30 kDa category. Conversely, Vycross released more of the shortest sHA fragment chains for all 3 low [molecular weight] categories,” write the study authors.4
The investigators concluded that most products using high molecular weight HA undergo significant HA chain degradation during the manufacturing process.
“These data continue to underscore the innovation that drives Revance’s aesthetics portfolio, including our investigational neuromodulator product, daxibotulinumtoxinA for injection, and the RHA Collection, which was launched in September 2020,” noted Roman Rubio, senior vice president of clinical development at Revance, in a press release announcing the posters.5
1. Humphrey S, Fabi S, Jones D, Gross T, Liu Y, Rubio R. Visualizing the elimination of glabellar lines following treatment with DaxibotulinumtoxinA for injection (DAXI). Poster presented at: 2021 American Academy of Dermatology Virtual Meeting Experience; April 23-25, 2021; Virtual. Poster 28216.
2. Ablon G, Shamban A, Weinkle S, Brown J, Liu Y. DaxibotulinumtoxinA for injection (DAXI) demonstrates consistent efficacy, duration, and safety in females independent of age: subgroup analysis from a large, phase 3 program. Poster presented at: 2021 American Academy of Dermatology Virtual Meeting Experience; April 23-25, 2021; Virtual. Poster 265448.
3. Glogau R, Kontis T, Liu Y, Gallagher CJ. DaxibotulinumtoxinA for injection (DAXI)-treated subjects show progressive improvement in static glabellar lines with repeated treatment. Poster presented at: 2021 American Academy of Dermatology Virtual Meeting Experience; April 23-25, 2021; Virtual. Poster 26550.
4. Mashburn J, Faivre J, Bourdon F. Evaluation of the impact of hyaluronic acid (HA) manufacturing technologies on HA chain degradation. Poster presented at: 2021 American Academy of Dermatology Virtual Meeting Experience; April 23-25, 2021; Virtual. Poster 28073.
5. Revance to present data on DaxibotulinumtoxinA for injection and hyaluronic acid fillers at American Academy of Dermatology VMX meeting 2021. News release. BioSpace. April 23, 2021. Accessed April 28, 2021. https://www.biospace.com/article/releases/revance-to-present-data-on-daxibotulinumtoxina-for-injection-and-hyaluronic-acid-fillers-at-american-academy-of-dermatology-vmx-meeting-2021/