Daxxify (daxibotulinumtoxinA) / Revance Therap - LARVOL DELTA

Phase 2a Study of DaxibotulinumtoxinA-lanm for Injection in Dynamic Forehead Lines and Glabellar Lines (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Revance Therapeutics, Inc.

New P2 trial

An Open Label, Study of DaxibotulinumtoxinA for Migraine Prevention (clinicaltrials.gov) - P=N/A | N=10 | Active, not recruiting | Sponsor: Ki Health Partners. LLC | Recruiting ➔ Active, not recruiting | N=20 ➔ 10

Enrollment change • Enrollment closed • CNS Disorders • Migraine • Pain

Influence of Novel Formulation in DaxibotulinumtoxinA on Efficacy for Treatment of Cervical Dystonia (AAN 2024) - "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.Design/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). 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."

Clinical • CNS Disorders • Dystonia • Movement Disorders

Efficacy Remaining at Time of Requested Retreatment Following Botulinum Toxin Treatment for Cervical dystonia: Potential for a New Treatment Paradigm with DaxibotulinumtoxinA (AAN 2024) - "These findings demonstrate, for the first time, a significant proportion of efficacy remained in patients who requested BoNT reinjection for their CD symptoms. With the long duration of benefit of daxibotulinumtoxinA, there is opportunity for a new approach whereby physicians can tailor treatments to individual patient needs and treat patients as their symptoms re-emerge at 12 weeks or beyond."

Clinical • CNS Disorders • Dystonia • Movement Disorders

Effects of DaxibotulinumtoxinA for Blepharospasm and Hemifacial Spasm (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Montefiore Medical Center | Trial primary completion date: Jul 2025 ➔ Apr 2026

Trial primary completion date • CNS Disorders

Complexing Protein-Free Botulinum Neurotoxin A Formulations: Implications of Excipients for Immunogenicity. (PubMed, Toxins (Basel)) - "Reportedly, the rate of antibody-mediated secondary non-response is lowest in complexing protein-free (CF) IncobotulinumtoxinA (INCO). Here, the published data and literature on the composition and properties of the three commercially available CF-BoNT/A formulations, namely, INCO, Coretox® (CORE), and DaxibotulinumtoxinA (DAXI), are reviewed to elucidate the implications for their potential immunogenicity...Presently, no data are available on the immunogenicity of CORE in human beings. It remains to be seen whether all three CF BoNT/A formulations demonstrate the same low immunogenicity in patients over a long period of time."

Journal • Review

Applications for Neurotoxins in the Face and Neck. (PubMed, Atlas Oral Maxillofac Surg Clin North Am) - No abstract available

Journal • Review • Aesthetic Medicine

Efficacy and Safety of DaxibotulinumtoxinA for Injection in Cervical Dystonia: ASPEN-1 Phase 3 Randomized Controlled Trial. (PubMed, Neurology) - P3 | "This study demonstrated that DAXI, at doses of 125U and 250U, is an effective, safe, long-acting, and well-tolerated treatment for CD."

Clinical • Journal • P3 data • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Pain

DaxibotulinimtoxinA for Treatment of Platysmal Neck Bands (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: Main Line Center for Laser Surgery

New P4 trial

Efficacy and Safety of DaxibotulinumtoxinA for Injection Over Successive Treatments in Adults With Cervical Dystonia in the Phase 3 ASPEN-1 and ASPEN-OLS Trials (TOXINS 2024) - "Responder rates as measured by Clinical and Patient Global Impression of Change scores (≥2-point improvement) at Weeks 4 or 6 also increased from ASPEN-1 (58.8% and 52.2%, respectively) to Cycle 4 of ASPEN-OLS (83.1% and 69.2%, respectively). Conclusions Repeat treatments with daxibotulinumtoxinA were efficacious, safe, and well tolerated, and demonstrated a favorable immunogenicity profile."

Clinical • P3 data • CNS Disorders • Dystonia • Movement Disorders • Musculoskeletal Pain • Pain

A Cell Penetrating Peptide Enhances Membrane Binding of Botulinum Neurotoxin Type A and Increases SNAP-25 Cleavage (TOXINS 2024) - "Introduction DaxibotulinumtoxinA-lanm for injection (daxiBoNT-A) is a newly approved BoNT-A product with a unique and novel formulation. An increase in SNAP-25 cleavage in the presence of RTP004 may yield a greater degree, and potentially a longer duration, of neuronal silencing for a given amount of applied neurotoxin. This supports the critical role of formulation excipients in the clinical performance of BoNT products."

CNS Disorders • Dystonia • Movement Disorders

Free of Complexing Proteins – Enough for Low Immunogenicity of Botulinum Neurotoxin Formulations? A Comparison of Excipients (TOXINS 2024) - "Results Presently, incobotulinumtoxinA, daxibotulinumtoxinA, and Coretox® are 3 commercially available BoNT-A formulations that are free of clostridial complexing proteins. Results from early clinical studies show antibodies against BoNT-A and RTP004 at low frequencies; however, the follow-up period is critically short, with a maximum of 3 injections.7 For Coretox, there are presently no data on the formulation’s immunogenicity in human beings. It remains to be seen whether all 3 CF-BoNT-A formulations show the same low immunogenicity in patients over a long period of time."

A Cell Penetrating Peptide (CPP), Synthesized to Match the Sequence of Revance Rtp004, Does not Decrease 150 Kd BoNT-A Toxin Adsorption to Surfaces (TOXINS 2024) - "Objective Revance Therapeutics has recently launched 50 and 100 units (U) of daxibotulinumtoxinA (daxiBoNT-A) to treat glabellar lines. Conclusions Data presented here indicate that inclusion of a cell penetrating peptide in a BoNT-A/daxiBoNT-A mock formulation does not prevent toxin adsorption. Moreover, the contribution of the CPP in the formulation is unclear."

Long-Term Safety of Repeat Treatments of DaxibotulinumtoxinA for Injection in Adults With Isolated Cervical Dystonia in Phase 3, Open-label, Multicenter ASPEN-OLS Trial (TOXINS 2024) - "Overall incidence of treatment-induced anti-drug antibodies was low, with no observed trend in incidence over successive doses. Conclusions Repeat treatment with daxibotulinumtoxinA was safe and well tolerated and demonstrated a favorable immunogenicity profile."

Clinical • P3 data • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders • Pain

Efficacy and Safety of DaxibotulinumtoxinA for Injection Over Successive Treatments in Adults With Cervical Dystonia in the Phase 3 ASPEN-1 and ASPEN-OLS Trials (TOXINS 2024) - P = 3 | N = 382 | "Repeat treatments with daxibotulinumtoxinA were efficacious, safe, and well tolerated, and demonstrated a favorable immunogenicity profile."

Clinical data • P3 data

Effects of DaxibotulinumtoxinA for Blepharospasm and Hemifacial Spasm (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Montefiore Medical Center

New P4 trial • CNS Disorders

Open Label, 6-month Study for High Frequency and Chronic Migraine, (clinicaltrials.gov) - P=N/A | N=10 | Recruiting | Sponsor: Ki Health Partners. LLC

Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

DaxibotulinumtoxinA Injection for Treatment of Adductor Spasmodic Dysphonia (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: University of California, San Francisco

Trial completion date • Trial primary completion date • Dysphonia • Otorhinolaryngology

Mitigation of risk of botulinum toxin A-induced blepharoptosis with hyperconcentrated glabellar injections. (PubMed, J Am Acad Dermatol) - No abstract available

Journal

Biochemical Stability and Microbial Control of Reconstituted DaxibotulinumtoxinA-lanm for Injection. (PubMed, Toxins (Basel)) - "No changes in recoverable 150 kDa neurotoxin (measured by enzyme-linked immunosorbent assay) were observed over 6 days of refrigeration. Bacterial growth or pathogen proliferation was not observed in DAXI reconstituted in preserved or unpreserved saline in both studies."

Journal

An Open Label, Study of DaxibotulinumtoxinA for Migraine Prevention (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: Ki Health Partners. LLC

New trial • CNS Disorders • Migraine • Pain

Open Label, 6-month Study for High Frequency and Chronic Migraine, (clinicaltrials.gov) - P=N/A | N=10 | Recruiting | Sponsor: Ki Health Partners. LLC

New trial • CNS Disorders • Migraine • Pain

DaxibotulinumtoxinA Injection for Treatment of Adductor Spasmodic Dysphonia (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: University of California, San Francisco | Withdrawn ➔ Recruiting

Enrollment open • Dysphonia • Otorhinolaryngology

Neuromodulators for Skin. (PubMed, Facial Plast Surg Clin North Am) - "Dermal and subdermal injections of dilute BoNTA has grown in popularity and been shown to improve skin texture and quality. Common targets for chemodenervation in facial nerve synkinesis are ipsilateral orbicularis oculi, mentalis, depressor anguli oris, buccinator, corrugator muscles, and the ipsilateral and/or contralateral frontalis."

Journal • Review • Aesthetic Medicine • CNS Disorders • Dermatology

A technology evaluation of the atypical use of a CPP-containing peptide in the formulation and performance of a clinical botulinum toxin product. (PubMed, Expert Opin Drug Deliv) - "The RTP004-neurotoxin formulation is the first CPP-containing product approved for clinical use. The potential for RTP004 to facilitate other therapeutic cargo molecules requires further research."

Journal