Q&A: Steve Yoelin, MD, on the Evolving Regulatory Landscape for Masseter Toxin

As interest in nonsurgical lower-face contouring continues to grow, treatment of masseter muscle prominence has become an increasingly common consideration in aesthetic dermatology. The recent FDA acceptance for review of a supplemental Biologics License Application for onabotulinumtoxinA (BOTOX Cosmetic) could represent an important step toward establishing an on-label framework for a treatment area that has historically been managed off-label. In this Q&A, Steve Yoelin, MD, an ophthalmologist based in Orange County, California, discussed the clinical evidence supporting the application, including findings from the pivotal M21-416 and M21-417 studies, and explored how a potential approval could influence injector education, patient counseling, safety considerations, and holistic facial treatment planning. Yoelin, who has over 25 years of experience in minimally invasive injectables and medical aesthetics, also addressed the importance of distinguishing aesthetic treatment of masseter prominence from treatment of functional conditions such as bruxism and temporomandibular joint–related symptoms.

Dermatology Times: Masseter neurotoxin injections have been an off-label staple for years. How would this potential FDA approval change conversations on practice liability, injector confidence, and patient trust?

Yoelin: Masseter neurotoxin injections have long been used in clinical practice, but FDA approval would represent an important regulatory milestone by establishing an on-label framework for this treatment area. Off-label use can create variability in treatment protocols, consent discussions, and patient expectations. An approved indication would give clinicians clearer administration guidance supported by clinical research, helping strengthen injector confidence and support more consistent conversations with patients about treatment goals, evidence, and trust.

Dermatology Times: What were some of the key findings reported in studies M21-416 and M21-417 that support this sBLA submission?

Yoelin: The sBLA submission is supported by two pivotal phase 3 studies, M21-416 and M217-417. Both studies met their primary endpoints, demonstrating statistically significant reductions in masseter muscle prominence (MMP) and visible softening and narrowing of the jawline compared with placebo. Patient-reported satisfaction also favored treatment: approximately 58% to 59% of patients treated with BOTOX Cosmetic reported being "Very Satisfied" or "Satisfied" with their lower facial contour, compared with 22% to 26% of patients in the placebo group. The overall safety profile was consistent with the established safety record of BOTOX Cosmetic across its approved aesthetic indications, with no new safety signals identified in the clinical program.

Dermatology Times: Compared to upper-face neurotoxin indications, what key safety considerations, anatomical landmarks, and dosage measures should dermatologists be mindful of while injecting into the masseter?

Yoelin: Assessment of facial shape is a critical component of patient evaluation. Typically, women exhibit a greater bi-zygomatic distance than bi-gonial distance, resulting in a heart-shaped or oval face. Conversely, men tend toward a more rectangular or trapezoidal shape, where the bi-gonial distance closely approaches or exceeds the bi-zygomatic distance. The recent BOTOX Cosmetic indication for the masseter muscle is highly effective in helping patients optimize their desired facial shape. The masseter is a muscle of mastication that often becomes significantly thickened when hypertrophied. When treating this area, injections should be placed in the lateral and inferior aspects of the muscle, just above the body of the mandible. It is crucial to avoid the risorius muscle, which sits closer to the zygoma, to prevent an asymmetric smile.
In the clinical trial, subjects received 3 injections of 8 units per masseter muscle, totaling 24 units per side and a cumulative dose of 48 units of BOTOX Cosmetic. Given the thickness of the muscle, the recommended technique involves injecting an 8-unit thread (approximately 1/4" in length) where the muscle is most prominent. Using a 1/2" small-bore needle, the injection should start at the bone while the patient's mouth is gently open to ensure the muscle is not contracted. Practitioners may also consider changing the needle frequently throughout the procedure. Results for masseter muscle hypertrophy treatments typically begin to take effect 2 weeks post-treatment.

Dermatology Times: Many patients presenting with masseter prominence also experience symptoms like TMJ discomfort or nocturnal bruxism. How does your approach and evaluation change when treating aesthetic lower-face contouring versus functional bite dynamics and pain?

Yoelin: It is important to note that BOTOX Cosmetic's facial shape indication is designed specifically to reduce the prominence of the masseter muscle. It is not an approved treatment for bruxism or TMJ-related discomfort.
Please keep this distinction in mind when offering this treatment option to patients. If patients complain of masseter prominence associated with bruxism or TMJ-related discomfort, they should be advised to consult an oral surgeon or a qualified TMJ specialist.

Dermatology Times: As the field is shifting away from single treatment areas and going toward holistic facial planning, how will this new indication overall meet the needs of patients and providers?

Yoelin: Aesthetic medicine has shifted from treating isolated areas to planning for whole-face harmonization and structural balance. If approved, masseter muscle prominence would become the fifth FDA-approved aesthetic indication for BOTOX Cosmetic, joining frown lines, forehead lines, crow’s feet, and platysma neck bands. It would also create an on-label lower-face option that could help providers plan treatment across the upper, mid, and lower face within a validated framework.

If approved, this indication would respond to growing interest in non-surgical jawline contouring while giving providers an on-label option for addressing masseter prominence as part of broader facial assessment and treatment planning. It could also help clinicians more consistently integrate lower-face narrowing with other aesthetic approaches, such as upper-face toxin treatment, midface volumization, and skin-tightening modalities, to support balanced, natural-looking outcomes.

Dermatology Times: Is there anything else you’d like to share with our audience today?

Yoelin: I’d add that as interest in jawline contouring continues to grow, it’s important not to view the masseter in isolation. Lower-face treatment should be considered within the context of the patient’s anatomy, functional concerns, and overall facial balance. Ongoing clinical evidence and injector education can help providers approach these conversations with greater confidence and help patients understand what treatment can realistically achieve.