NUCEIVA Powder for solution for injection Ref.[27531] Active ingredients: Botulinum toxin type A

Pharmacotherapeutic group: Muscle relaxants, other muscle relaxants, peripherally acting agents
ATC code: M03AX01

Mechanism of action

Botulinum toxin type A (Clostridium botulinum neurotoxin) blocks peripheral acetylcholine release at presynaptic cholinergic nerve terminals by cleaving SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within the nerve endings, thereby leading to denervation of the muscle and a flaccid paralysis.

After injection, there is an initial rapid high-affinity binding of toxin to specific cell surface receptors. This is followed by transfer of the toxin across the plasma membrane by receptor-mediated endocytosis. Finally, the toxin is released into the cytosol with progressive inhibition of acetylcholine release. Clinical signs are manifest within 2-3 days, with peak effect seen within 4 weeks of injection.

Recovery after intramuscular injection takes place normally within 12 weeks of injection as nerve terminals sprout and reconnect with the endplates.

Clinical efficacy and safety

Glabellar lines

540 patients with moderate to severe glabellar lines seen at maximum frown who felt their glabellar lines had an important psychological impact (on mood, anxiety/or depressive symptoms) have been included in the European/Canadian clinical study.

NUCEIVA injections significantly reduced the severity of glabellar lines by 1 point or greater at maximum frown for up to 139 days, as measured by the investigator assessment of glabellar line severity at maximum frown.

Table 2. Primary Efficacy Endpoint – Glabellar Line Scale Score of 0 (none) or 1 (mild) at Day 30 by Investigator Assessment at Maximum Contraction, PP Population:

Glabellar Line Scale (GLS); 0=no lines, 1=mild, 2=moderate, 3=severe

Two days after injection, 12.2% (6/49) of placebo, 57.0% (139/244) Botox treated patients and 54.2% (130/240) of NUCEIVA were considered by investigators as treatment responders (none or mild severity at maximum frown).

Table 3. Exploratory Efficacy Endpoint – Glabellar Line Scale Score of 0 (none) or 1 (mild) at Day 30 by Investigator Assessment at Maximum Contraction for NUCEIVA Treated Subjects, by Baseline GLS Score at Maximum Contraction, ITT Population:

Table 4. Exploratory Efficacy Endpoint – Glabellar Line Scale Score of 0 (none) or 1 (mild) at Day 30 by Investigator Assessment at Maximum Contraction for NUCEIVA Treated Subjects, by Baseline GLS Categories at Rest, ITT Population:

NUCEIVA injections also reduced the severity of glabellar lines at rest, an exploratory endpoint.

Table 5. Exploratory Efficacy Endpoint – Glabellar Line Scale Score >/=2 points better at day 30 by Investigator Assessment At Rest, PP Population:

There are limited phase 3 clinical data with NUCEIVA in patients older than 65 years.

Duration of response in the phase 3 study was 139 days, based on a 1 point GLS improvement. A total of 922 patients participated in two 1 year open label uncontrolled studies, and over the course of these studies, the average patient received 3 treatments.

The psychological impact of glabellar lines was confirmed at study entry and although a beneficial effect could not be demonstrated on psychological wellbeing, significant effects on patient reported outcomes were demonstrated as compared to placebo. Further, the effects of NUCEIVA on psychological wellbeing and patient reported outcomes were comparable to BOTOX, the active control used in the pivotal study.