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Abstract Details

Influence of Novel Formulation in DaxibotulinumtoxinA on Efficacy for Treatment of Cervical Dystonia
Movement Disorders
P1 - Poster Session 1 (8:00 AM-9:00 AM)

Conventional BoNT products used to treat cervical dystonia (CD) tend to have a similar clinical profile with a duration of efficacy of approximately 12 weeks and are formulated using the common excipient human serum albumin (HSA) in addition to a salt or sugar. DaxibotulinumtoxinA for injection (DAXI) is a newly approved BoNT/A product with a novel formulation without HSA. Rather DAXI contains a proprietary 35-amino acid peptide (RTP004) which is known to increase thermostability and help prevent surface adsorption. In clinical trials for CD DAXI at a dose of 250U, which contains approximately half the amount of core neurotoxin as the 236U approved dose for onabotulinumtoxinA for CD, showed a median time to loss of efficacy of 20 weeks.

To understand the influence of formulation on the clinical performance of botulinum toxin (BoNT) products.

The effect of RTP004 and HSA on BoNT/A binding to neuronal cells was assessed via cell-binding assays in N2a cells (mouse) and SiMa cells (human). SNAP-25 cleavage was assessed by western blot after incubation with a fixed concentration of BoNT and increasing concentrations of RTP004 or HSA.

The 150kD BoNT/A binding to the surface of neuronal cells was increased by 2- to 3-fold with increasing amounts of RTP004 compared with BoNT/A binding alone. HSA did not increase the amount of toxin bound to cells at any concentration tested. Additionally, RTP004 produced a dose-dependent increase in the cleavage of SNAP-25 in cells exposed to a constant concentration of BoNT/A compared to BoNT/A alone or BoNT with HSA.

We have demonstrated that the interaction of RTP004 with the 150-kDa BoNT/A can enhance binding to neurons and cleavage of the intracellular substrate, SNAP-25. This data illustrates the importance of formulation on the clinical performance of a BoNT product and the impact of the novel peptide excipient in DAXI.

Conor Gallagher (Revance Therapeutics)
No disclosure on file
Han Lee, MD (Kaiser Permanente) Dr. Lee has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Revance.
Andre Batista (Revance) No disclosure on file