Each vial of JEUVEAU (prabotulinumtoxinA-xvfs) for injection contains 100 Units of botulinum toxin type A neurotoxin complex, humanserum albumin (0.5 mg), and sodium chloride (0.9 mg) in a sterile, vacuum-dried form without a preservative.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

JEUVEAU blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, andinhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking

and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, JEUVEAUproduces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy,

axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the musclemay occur, thus slowly reversing muscle denervation produced by JEUVEAU.

12.2 Pharmacodynamics

No formal pharmacodynamic studies have been conducted with JEUVEAU.

12.3 Pharmacokinetics

Using currently available analytical technology, it is not possible to detect JEUVEAU in the peripheral blood following intramuscular injectionat the recommended doses.

No drug interaction studies have been conducted with JEUVEAU.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been conducted to eva luate the carcinogenic, mutagenic or impairment of fertility potential of JEUVEAU.

14 CLINICAL STUDIES

Two randomized, multi-center, double-blind, placebo-controlled trials (EV-001 [NCT02334423] and EV-002 [NCT02334436]) of identicaldesign were conducted to eva luate JEUVEAU for use in the temporary improvement of the appearance of moderate to severe glabellar facial

lines. These trials enrolled 654 subjects, randomized 3 to 1 to a single treatment with JEUVEAU (n=492) or placebo (n=162).

The trials enrolled healthy adults (ranging in age from 18 to 81) with glabellar lines of at least moderate severity at maximum frown. The trialsexcluded subjects who had ptosis, deep dermal scarring, or an inability to substantially lessen glabellar lines even by physically spreading

the glabellar lines apart. Injection volume was 0.1 mL/injection site, for a dose/injection site in the active treatment groups of 4 Units.

Subjects were injected intramuscularly at five sites, one in the procerus muscle and two in each corrugator supercilii muscle, for a total dosein the active treatment groups of 20 Units.

The primary efficacy endpoint was measured at Day 30 and was defined as the proportion of subjects achieving ≥2-grade improvement frombaseline at maximum frown, as assessed independently by both the investigator and the subject using the Glabellar Line Scale (GLS). The

GLS is a 4-point grading scale (0=none, 1=mild, 2= moderate, 3=severe). The results of these two efficacy trials are presented below (SeeTable 3).

The mean age was 51 years, with 68 subjects (10%) ≥ 65 years of age. Most of the subjects were women (91%), and a majority of thesubjects were white (84%).