botulinum toxin E (AGN-151586) / AbbVie - LARVOL DELTA

A Study to Evaluate Sequential Administration of Injections of AGN-151586 Followed by BOTOX in Adult Participants for Treatment of Glabellar Lines (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

Comparative protein engineering redirects the specificity of Clostridium botulinum proteases. (PubMed, Cell Chem Biol) - "Botulinum neurotoxin serotypes A and E (BoNT/A and BoNT/E) cleave SNAP25 and are widely used in therapeutic applications...Importantly, both engineered proteases retain their altered substrate preferences under physiologically relevant substrate and salt concentrations. Together, these findings establish comparative protein engineering as an effective framework for retargeting botulinum neurotoxin proteases."

Journal

A Study to Assess the Safety and Efficacy of AGN-151586 Injections for the Treatment of Moderate to Severe Forehead Lines (FHL) in Adult Participants (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate Sequential Administration of Injections of AGN-151586 Followed by BOTOX in Adult Participants for Treatment of Glabellar Lines (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: AbbVie

New P1 trial

A Study to Assess the Safety and Efficacy of AGN-151586 Injections for the Treatment of Moderate to Severe Forehead Lines (FHL) in Adult Participants (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: AbbVie

New P2 trial

Rapid Results With TrenibotulinumtoxinE For the Treatment of Glabellar Lines in Toxin-naïve Adults: Safety, Efficacy, and Satisfaction Findings From a Pivotal Phase 3 Study. (PubMed, Aesthet Surg J) - "TrenibotE was well tolerated and improved GL severity in toxin-naïve participants, with rapid results and short duration of effect. Participants were satisfied with overall treatment and their natural-looking results."

Journal • P3 data

AI-redesigned starting points and outcomes enhance protein evolution. (PubMed, Nature) - "Proteases evolved from the redesigned starting point reached higher catalytic efficiency and stability while minimizing native substrate cleavage, achieving more than 79-fold greater selected specificity for ataxin-2 than the best-performing variant evolved from WT BoNT/E. This study establishes a practical workflow using AI-redesigned starting points to evolve enzymes with improved properties compared with those evolved from natural proteins, with broad implications for protein science."

Journal

BoNT/E-associated protein disrupts intestinal epithelial barrier integrity to facilitate transcytosis. (PubMed, Front Mol Biosci) - "The results suggest that P80 contributes to BoNT/E intestinal absorption and may serve as a promising bioenhancer for improving mucosal delivery of therapeutic proteins and other hydrophilic macromolecules. Further mechanistic and in vivo studies are warranted to evaluate its translational potential."

Journal • CLDN1

Safety and Efficacy of TrenibotulinumtoxinE for Moderate-to-Severe Glabellar Lines: A Phase 2b, Double-Blind, Placebo-Controlled, Dose-Escalation Study. (PubMed, Aesthet Surg J) - "TrenibotulinumtoxinE was efficacious and well tolerated across a range of doses in treating moderate-to-severe GL."

Journal • P2b data

A belt-buckle checkpoint regulates the onset of botulinum neurotoxin intoxication. (PubMed, Nat Commun) - "The more flexible BoNT/E belt promotes quicker LC translocation into the neuronal cytosol, leading to faster onset of action compared to BoNT/A...Conversely, locking the belt-buckle with an antibody neutralizes BoNT/A. Our findings open avenues for developing fast-acting BoNTs and effective countermeasures."

Journal

Safety and Efficacy of TrenibotulinumtoxinE for Treating Glabellar Lines in Toxin Naïve Participants: Results from a Multicenter Phase 3 Study (CDA 2026) - "TrenibotE 700 U effectively improved GL severity in toxin-naïve participants, demonstrating rapid onset and short duration effect. TrenibotE treatment was well tolerated, with AEs being predominantly non-serious, mild, and unrelated to study treatment. Takeaway Message: TrenibotE 700 U effectively improved GL severity in toxin-naïve participants, demonstrating rapid onset and short duration effect."

Clinical • P3 data

Botulinum toxin type E alleviates trigeminal neuropathic pain via modulation of the HIF-1α-NLRP3 pathway. (PubMed, Front Toxicol) - "Intraganglionic injection of PX-478, a HIF-1α inhibitor, similarly attenuated mechanical allodynia, downregulated NLRP3 expression, and decreased IL-1β, IL-18, TNF-α, and IL-6 levels in the iTG. Collectively, these findings demonstrate that modulation of the HIF-1α-NLRP3 pathway in the iTG plays a critical regulatory role in neuropathic pain development and suggest that BoNT/E may serve as a promising therapeutic strategy for managing chronic neuropathic pain."

Journal • Neuralgia • Oncology • Pain • HIF1A • IL18 • IL1B • IL6 • NLRC5 • NLRP3 • TNFA

In Vivo Model of Short-Term Efficacy and Favorable Safety of Botulinum Toxin Type E Compared with Type A. (PubMed, Toxins (Basel)) - "Neither BoNT/E nor BoNT/A showed diffusion to adjacent muscles or changes in body weight. These findings suggest that BoNT/E provides rapid onset, short duration, and favorable safety, supporting its potential as an alternative therapeutic option for indications requiring temporary muscle relaxation with minimized long-term adverse effects."

Clinical • Journal • Preclinical • Fibrosis • Immunology • Inflammation • Muscular Atrophy

Artificial Intelligence in Botulinum Toxin Injections: A Mini-Review of Current Applications, Challenges, and Translational Perspectives. (PubMed, Cureus) - "However, this mini-review synthesizes the most recent and relevant high-quality studies and provides a timely, structured overview of emerging AI applications to support clinical decision-making in BoNT practice. Future translation should prioritize prospective validation, formulation-aware dose modeling, transparent governance, and physician-supervised implementation."

Journal • Review • Aesthetic Medicine • CNS Disorders • Dermatology • Dystonia • Movement Disorders

High sensitivity of iPSC-derived motor neurons to the human-relevant Botulinum Neurotoxin serotypes E and F. (PubMed, Neurotoxicology) - "Sensitive, serotype‑independent human cell‑based alternatives are particularly needed for the emerging serotypes BoNT/E and BoNT/F, for which no validated in vitro potency assay currently has been reported...These results confirm human iPSC‑derived motor neurons as a sensitive, physiologically relevant model capable of detecting four medically important BoNT serotypes. While Western blotting provides robust determination of potency, this cellular model well suited for adaptation to serotype-independent high‑throughput formats, paving the way for animal‑free BoNT potency testing."

Journal • VAMP2

Consensus Computational Immunogenicity Modelling of Botulinum Neurotoxin Serotypes: Cross-Platform Validation, Uncertainty Quantification, and Relative Risk Assessment. (PubMed, Toxicon) - "These predictions remain subject to the inherent simplifications of computational models relative to the complexity of human immune responses. Nonetheless, this convergent, cross-platform evidence establishes a robust risk hypothesis, underscoring the need for enhanced clinical immunogenicity monitoring for BoNT/E."

Journal • Relative risk

Non-ablative resurfacing yearly reduces risks of NMSC Low-Level light/photobiomodulation actually works: what I do myself BontE: The hung Jury Non-Ablative ER Yag for skin laxity (AAD 2026) - No abstract available

Dermatology

Safety and Efficacy of TrenibotulinumtoxinE Following Repeat Treatments for Glabellar Lines: Findings From an Open-Label Phase 3 Study (AAD 2026) - "TrenibotE demonstrated consistent efficacy and AE profiles over 3 open-label treatment cycles, with no new safety concerns identified. The favorable benefit:risk profile was consistent with double-blind pivotal Phase 3 studies."

Clinical • P3 data

Mind the gap: a German case study on the discrepancy between geographic accessibility and real-world utilization of botulinum toxin therapy. (PubMed, Front Neurol) - "Additionally, the German Botulinum Toxin Working Group (Arbeitskreis Botulinumtoxin e. V.; AK-BoNT) performed an anonymous online survey of its members, who treat with BoNT, between November 2023 and March 2024 to document experiences, identify perceived barriers, and explore potential improvements in BoNT-A therapy...Interestingly, even in a well-resourced system with broad geographic access to specialized care, significant treatment gaps may persist. Recommendations include standardized reimbursement structures, improved education, and increased cross-sector collaboration."

Journal • Real-world evidence • Cardiovascular • CNS Disorders • Movement Disorders

Evaluation of a Cell-Based Potency Assay for Detection of the Potency of TrenibotulinumtoxinE® (TrenibotE). (PubMed, Toxins (Basel)) - "The repeatability was 2.4%, which is well within the acceptance criterion of ≤8%. (4) The evaluation was carried out within a single laboratory under controlled conditions; the new CBPA meets all acceptance criteria and can be used for BoNT/E potency determination."

Journal • Neuroblastoma • Oncology • Solid Tumor

Evoking Powers of Occupation From Occupation-Based Practices After Stroke: A Scoping Review. (PubMed, OTJR (Thorofare N J)) - "Findings revealed that OBPs can evoke all nine powers of occupation proposed by Bontje, which include therapeutic change, self-expression, participation, and habit formation. Hospital-based practices primarily focused on enhancing physical and cognitive functions, whereas community-based approaches concentrated on fostering independence and social integration. In summary, OBPs are essential tools in stroke rehabilitation, offering a comprehensive approach to address the physical, emotional, and social needs of individuals with stroke during their recovery journey."

Journal • Cardiovascular

Beyond Structural Divergence: Multiscale Computational Immunogenicity Modelling of Botulinum Neurotoxin E and Cross-Reactivity in Botulinum Neurotoxin A Primed Hosts. (PubMed, Toxicon) - "Population coverage analyses predicted BoNT/E epitopes would engage 94% of individuals globally, increasing to 98% with A+E. These molecular findings identify BoNT/E as an epitope-dense, highly accessible, and cross-reactive antigen with amplified immunogenicity under simulation, necessitating further exploration with longer clinical trials."

Journal

A Study to Assess the Adverse Events of Intramuscular Injections of AGN-151586 and OnabotulinumtoxinA in Adult Participants for the Change of Glabellar Lines (GL) (clinicaltrials.gov) - P1 | N=132 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Adverse events • Trial completion

Anti-nociceptive activities of novel long-acting SNARE-inactivating biotherapeutics (IHC 2025) - "Methods Two approaches were pursued: (1) protein engineering of a composite toxin by recombinantly fusing the light chain of BoNT/E (LC/E) to BoNT/A, creating LC/E-BoNT/A, and (2) gene therapy, identifying a sensory neuron specific Pirt (phosphoinositide-interacting regulator of TRP) promoter to drive long-term expression of LC/A via a lentiviral vector...At the highest non-paralytic dose, it outperformed both BoNT/A and repeated systemic administration of pregabalin...Moreover, targeted viral expression of LC/A in sensory neurons yielded long-lasting inhibition of pain mediator release. Conclusion These two strategies—chimeric protein design of LC/E-BoNT/A and targeted gene delivery using a Pirt promoter—demonstrate significant potential for developing safe, locally administered, and durable treatments for chronic pain."

Migraine

Targeting the Enzymatic Site of Botulinum Neurotoxin Type E With 8-Hydroxyquinolinol-Based Inhibitors: In Silico, In Vitro, and In Vivo Evaluation. (PubMed, Drug Dev Res) - "This study showed that these 8-HQ derivatives had the potency to inhibit BoNT/E by interacting with the active site. Further studies could lead to the development of undiscovered postexposure therapeutics against this deadly neurotoxin."

Journal • Preclinical • Developmental Disorders