botulinum neurotoxin type A gel formulation (RT001) / Crown Labs - LARVOL DELTA

RTP004 Peptide Binds to Botulinum Neurotoxin, Increases Cell Surface Binding, and Enhances Cellular SNAP-25 Cleavage. (PubMed, Toxins (Basel)) - "RTP004 also increased binding of BoNT to the synaptosomal cell membrane and enhanced cleavage of SNAP-25 in a dose-dependent manner. These findings demonstrate that RTP004, not the excipient HSA common in other BoNT/A1 drug products, enhances binding of BoNT to the cell surface, facilitates internalization of BoNT into the cell, and increases SNAP-25 cleavage."

Journal

BLEXI: DaxibotulinumtoxinA for Blepharospasm (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: University of Pennsylvania

New P2 trial • CNS Disorders

DaxibotulinumtoxinA for Injection in Adults with Cervical Dystonia: Clinical Insights from a Real-World Early Experience Program. (PubMed, Mov Disord Clin Pract) - "In this real-world setting, DAXI demonstrated extended clinical benefit and a favorable safety profile."

Journal • Real-world evidence • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders • Pain

A novel peptide excipient stabilizes DaxibotulinumtoxinA. (PubMed, Int J Pharm) - "In combination with polysorbate 20 (PS20), RTP004 efficiently and completely prevents surface adsorption of the 150 kDa core neurotoxin and stabilizes the biologic drug substance during manufacturing processes, even at concentrations 10- to 100-fold less than those used for HSA in commercial BoNTA products. Thus, the combination of RTP004 and PS20 forms the basis for a novel and effective BoNTA formulation, removing the need for HSA and thereby avoiding its theoretical safety risks and documented limitations."

Journal

Efficacy and safety of DaxibotulinumtoxinA for injection in adults with cervical dystonia: Pooled global analysis of ASPEN-1 and ASPEN-1-CN randomized trials. (PubMed, Parkinsonism Relat Disord) - "This pooled analysis of two phase 3 trials demonstrates that DAXI is an effective, safe, and long-acting treatment for CD. Key adverse events occurred at rates lower than prior pivotal trials of BoNTs for CD."

Clinical • Journal • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders

Reply to letter re: "A randomized, double-blind, placebo-controlled trial of daxibotulinumtoxinA for injection for the treatment of upper limb spasticity in adults after stroke or traumatic brain injury". (PubMed, PM R) - No abstract available

Clinical • Journal • Cardiovascular • CNS Disorders • Movement Disorders • Vascular Neurology

Long-Term Safety and Efficacy of Repeat Treatments with DaxibotulinumtoxinA in Cervical Dystonia: Results from the ASPEN-Open-Label Study. (PubMed, Mov Disord Clin Pract) - P3 | "DAXI was safe and efficacious over repeated treatments in adults with CD. Adverse event rates were similar to or potentially lower compared with conventional BoNTs."

Journal • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders • Pain

Reply to Trosch et al. Comment on "Dashtipour et al. Dysphagia and Muscle Weakness Secondary to Botulinum Toxin Type A Treatment of Cervical Dystonia: A Drug Class Analysis of Prescribing Information. Toxins 2024, 16, 442". (PubMed, Toxins (Basel)) - "We thank Trosch et al [...]."

Journal • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders

Efficacy Remaining at Time of Requested Re-Treatment for Cervical Dystonia: A Potential New Treatment Paradigm with DaxibotulinumtoxinA. (PubMed, Toxins (Basel)) - "A significant proportion of CD patients wished to be re-treated with efficacy still remaining from prior BoNT injections as early symptoms re-emerged. With the overall clinical profile of DAXI, physicians can safely provide individualized treatment regimens based on the treatment goals or symptomatic needs of their patients."

Clinical • Journal • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders

Real-world Evidence of Adding Atogepant to OnabotulinumtoxinA for Control of Chronic Migraine: A Retrospective Chart Review (P4-12.001). (PubMed, Neurology) - "Merle Diamond has received research support from Allergan. Merle Diamond has received personal compensation in the range of $500-$4,999 for serving as a Course Directory, Speaker with Diamond Research & Educational Foundation."

HEOR • Journal • Real-world evidence • Retrospective data • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Migraine • Pain

Dysphagia and Muscle Weakness Secondary to Botulinum Toxin Type A Treatment of Cervical Dystonia: A Drug Class Analysis of Prescribing Information. (PubMed, Toxins (Basel)) - "Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia."

Journal • CNS Disorders • Dystonia • Gastrointestinal Disorder • Movement Disorders

A randomized, double-blind, placebo-controlled trial of DaxibotulinumtoxinA for Injection for the treatment of upper limb spasticity in adults after stroke or traumatic brain injury. (PubMed, PM R) - "Results from this Phase 2 study indicate that DAXI 500 U is effective and well tolerated for treatment of adults with ULS."

Clinical • Journal • Cardiovascular • CNS Disorders • Movement Disorders • Vascular Neurology

Clinical Benefits of DaxibotulinumtoxinA for Injection: Beyond Glabellar Line Effacement? (PubMed, Dermatol Surg) - "Advances in BoNTA technology can provide patients with greater options for treatment outcomes. The potential for enhanced localized effects with DAXI may contribute to more precise and targeted effects on muscle activity and additional aesthetic benefits to patients."

Journal • Review

Achieving Durable Forehead Line Outcomes With DaxibotulinumtoxinA: Early Experience in Real-World Clinical Practice. (PubMed, Aesthet Surg J Open Forum) - "With previous generations of BoNT-A products, some degree of migration from the upper frontalis injection sites and/or the glabella injection sites into the mid and low frontalis is sufficient to prevent this effect, but the precision of DAXI demands that these fibers be more deliberately addressed with a larger number of individual injections. Through the use of more injection points, a wider area of treatment, and customization to fit patient needs, duration similar to that observed in clinical studies (20.9 weeks) can be achieved using between 20% and 33% fewer units of DAXI."

Journal • Real-world • Real-world evidence

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

Optimized Aesthetic Outcomes When Treating Glabellar Lines with Botulinum Toxin Type A: GLO 3 + 2: A Precise Technique Based on Anatomy. (PubMed, Plast Reconstr Surg Glob Open) - "Injection sites above the brow or that do not target the precise location of the muscles in the glabellar complex are likely to inadvertently expose the frontalis to botulinum toxin type A and result in undesirable aesthetic outcomes. Because the frontalis is a strong determinant of aesthetic outcomes, it is important to consider the overall effects of the interactions between the eyebrow depressors and the opposing forces of the frontalis on brow outcomes in both the resting brow position and during dynamic brow movement."

Journal

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

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

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

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

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