Table 2.
Studies investigating high doses of BoNT-A for the treatment of moderate-to-severe (GLS score 2–3) glabellar lines.
| ABO | ONA | INCO | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| [17] | [18] | [19] | [20] | [21] | ||||||
| STUDY DESIGN | ||||||||||
| Dose, U | 120 | 50, 75, 100, 125 | 20, 40, 60, 80 | 20, 50, 75 | 20, 60, 100 | |||||
| Increase vs. on-label dose | 2.4-fold | Up to 2.5-fold | Up to 4-fold | Up to 3.75-fold | Up to 5-fold | |||||
| Volume of injection per injection point | 0.08 mL | 0.05 mL | 0.05 mL | 0.05 mL | 0.05 mL | |||||
| Type of trial | Open-label, single-arm, pilot (IIS) | Phase 2, randomized, placebo-controlled | Randomized, placebo-controlled | Phase 2, randomized | Phase 4, randomized (IIS) | |||||
| No. of subjects | 30 | 399 (~80 per group) | 226 | 151 | 38 b | |||||
| Females, % | 77 | 88 | 100 | 87 | 82 b | |||||
| Severe GLS a at baseline, % | 53 | 68 | 60 | 85 | – | |||||
| Follow-up period, months | ~10 (300 days) | ~9 (36 weeks) | ~11 (48 weeks) | ~6–12 c | 12 | |||||
| EFFICACY | ||||||||||
| Scale | 4-point categorical scale |
4-point photographic scale |
4-point Facial Wrinkle Scale |
4-point Facial Wrinkle Scale |
5-point Merz Scale |
|||||
| ≥2-grade improvement + composite responder d, % | Day 30 (Week 4) 120 U: 63 |
Week 4 PBO: 3 50 U: 80 ‡ 75 U: 89 ‡ 100 U: 90 ‡ 125 U: 95 ‡ |
Not reported | Not reported | Not reported | |||||
| ≥1-grade improvement from baseline, % |
Day 150 (Week 21.4) 120 U: 62 |
Week 24 PBO: 5 50 U: 53‡ 75 U: 65‡ 100U: 58‡ 125 U: 69‡ |
Week 36 PBO: 0 50 U: 18 ‡ 75 U: 26 ‡ 100 U: 35 ‡ 125 U: 31 ‡ |
Week 24 PBO: 0 20 U: 16 40 U: 32 * 60 U: 31 NS 80 U: 39 * |
Week 28 e PBO: 0 20 U: ~10 40 U: ~20 * 60 U: <20 NS 80 U: ~20 * |
Week 36 e PBO: 0 20 U: <10 40 U: <10 NS 60 U: <10 NS 80 U: <10 NS |
No responder rates reported for INCO | |||
|
Week 24 (Day 170, estimated from Kaplan-Meier graph) 20 U: not shown 50 U: ~76 75 U: ~83 |
Week 36 (Day 250 estimated from Kaplan-Meier graph) 20 U: not shown 50 U: ~5 75 U: ~15 |
Week 24 (Day 170, estimated from Kaplan-Meier graph) 20 U: ~14 f 60 U: ~81 f 100 U: ~100 f |
Week 36 (Day 250 estimated from Kaplan-Meier graph) 20 U: 0 f 60 U: ~19 f 100 U: ~55 f |
|||||||
| Median time to return to baseline severity, weeks | 120 U: 21.4 g | 50 U: 32.3 h
75 U: 34.3 h 100 U: 36.0 h 125 U: 36.6 h |
PBO: 9.1 i
20 U: 19.7 i 40 U: 24.1 i 60 U: 24.1 i 80 U: 24.0 i |
20 U: 25.3 j
50 U: 26.4 j 75 U: 30.0 j |
20 U: 17.1 f,k
60 U: 25.7 f,k 100 U: 38.6 f,k |
|||||
| SAFETY | ||||||||||
| Safety summary | 3 drug-related AEs, all mild in severity and transient | Generally similar across dose groups; no drug-related SAEs | Similar between dose groups | Generally similar across dose groups; no SAEs | All AEs were mild with no apparent dose-proportional effect | |||||
| Ptosis AEs | No lid or brow ptosis | 4 cases of lid ptosis (2 mild, 2 moderate); all resolved; 1.3% of subjects (75 U), 2.5% (100 U), 1.2% (125 U) |
Open-label phase 1 lid ptosis; 14.3% of 7 subjects (80U), mild, resolved Double-blind phase 1 brow ptosis; 2.0% (20U), mild, resolved |
2 cases of lid ptosis; 1.3% of subjects overall (dose groups not reported) |
No ptosis reported | |||||
Standard doses are marked bold; ‡ p < 0.001 vs. placebo; * p < 0.05 vs. standard dose of 20 U; a.—Assessed by investigator/trained observer at maximum frown, b.—n = 50 patients were randomized and treated at least once; efficacy analysis was based on the 38 subjects who completed the study (subjects who dropped out after treatment were not analyzed), c—Subjects were required to remain in the study for a minimum of 180 ± 7 days and a maximum of 360 ± 7 days, d.—Severity grade of none or mild at maximum frown on both investigator- and subject-assessed scales concurrently, e.—Responder rates at Week 28 and Week 36 for ONA were estimated from the graph presented in the poster, f.— Severity improvement was evaluated on a 5-point scale, g.—Median time until return to score 2 or 3 among responders (defined as ≥2-grade improvement on a 4-point categorical scale from baseline), based on Kaplan-Meier analysis, h.—Median time until return to baseline from a none or mild (score 0 or 1) response, i.—Median time until return to baseline in Week 4 responders (defined as ≥1-grade improvement from baseline at Week 4), j.—Median time until return to baseline in responders (defined as ≥1-grade improvement from baseline), k.—Median time until return to baseline score from individual’s investigator-graded maximal contraction score. ABO, abobotulinumtoxinA; AE, adverse event; CI, confidence interval; GLS, glabellar line severity; IIS, investigator-initiated study; INCO, incobotulinumtoxinA; NS, not statistically significant; ONA, onabotulinumtoxinA; PBO, placebo; U, potency units (not interchangeable between products).