Injectable DaxibotulinumtoxinA for the Treatment of Glabellar Lines: A Phase 2, Randomized, Dose-Ranging, Double-Blind, Multicenter Comparison With OnabotulinumtoxinA and Placebo

Carruthers, Jean; Solish, Nowell; Humphrey, Shannon; Rosen, Nathan; Muhn, Channy; Bertucci, Vince; Swift, Arthur; Metelitsa, Andrei I.; Rubio, Roman G.; Waugh, Jacob M.; Quiring, John; Shears, Gill; Carruthers, Alastair

doi:10.1097/dss.0000000000001206

Cited by 41 publications

(39 citation statements)

References 4 publications

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“…On the basis of available preclinical data, a BoNT formulation containing as little clostridial protein as possible is desirable as it may avoid stimulating the host immune response leading to nAb formation and clinical nonresponse [1]. Three BoNT-A products are approved by the FDA for therapeutic use: onabotulinumtoxinA (onaBoNT-A; BotoxÒ; Allergan Pharmaceuticals), abobotulinumtoxinA (aboBoNT-A; Dys-portÒ; Ipsen Biopharm Ltd; Galderma Ltd), and incobotulinumtoxinA (incoBoNT-A; XeominÒ; Merz Pharmaceuticals GmbH) [17][18][19]; a fourth BoNT-A product, daxibotulinumtoxinA (dax-iBoNT-A; Revance Therapeutics), is currently under regulatory review for a nontherapeutic indication [72]. These products vary in the amount of accessory proteins and the excipients (e.g., albumin; Table 1) [17][18][19].…”

Section: Immunogenicity Of Accessory Proteinsmentioning

confidence: 99%

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications

Carr¹,

Jain²,

Sublett

2021

Adv Ther

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Botulinum neurotoxins (BoNTs) are proteins produced by bacteria of the Clostridium family. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism. There are seven serotypes of BoNT (serotypes A-G); BoNT-A and BoNT-B are the botulinum toxin serotypes utilized for therapeutic applications. Treatment with BoNT injections is used to manage chronic medical conditions across multiple indications. As with other biologic drugs, immunogenicity after long-term treatment with BoNT formulations may occur, and repeated use can elicit antibody formation leading to clinical nonresponsiveness. Thus, approaching BoNT treatment of chronic conditions with therapeutic formulations that minimize stimulating the host immune response while balancing patient responsiveness to therapy is ideal. Immunogenicity is a clinical limitation in many settings

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Section: Immunogenicity Of Accessory Proteinsmentioning

confidence: 99%

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications

Carr¹,

Jain²,

Sublett

2021

Adv Ther

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“…Injectable daxibotulinumtoxinA (RT002) is an investigational BoNT that is in clinical development for the treatment of cervical dystonia, glabellar lines,5 and plantar fasciitis 6. Injectable daxibotulinumtoxinA is a purified 150 kDa BoNT type A (RTT150) that is devoid of accessory proteins and formulated with a proprietary stabilizing excipient peptide (RTP004) in a lyophilized powder.…”

Section: Introductionmentioning

confidence: 99%

“…In clinical studies, injectable daxibotulinumtoxinA has shown a prolonged duration of response in the treatment of glabellar lines5, 9—with a significantly longer median duration of response than onabotulinumtoxinA (24 weeks versus 19 weeks; p = 0.030) when daxibotulinumtoxinA was used at the dose being evaluated in phase 3 glabellar line trials (40 U) and onabotulinumtoxinA was used at the dose for which it is approved for glabellar lines (20 U) 5…”

Section: Introductionmentioning

confidence: 99%

Injectable DaxibotulinumtoxinA in Cervical Dystonia: A Phase 2 Dose‐Escalation Multicenter Study

Jankovic

Truong

Patel³

et al. 2018

Movement Disord Clin Pract

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BackgroundInjectable daxibotulinumtoxinA (an investigational botulinum toxin, RT002) may offer a more prolonged duration of response—and therefore less frequent dosing—than onabotulinumtoxinA.ObjectivesTo perform a phase 2, open‐label, dose‐escalation study to assess the efficacy and safety of daxibotulinumtoxinA in cervical dystonia.MethodsSubjects with moderate‐to‐severe isolated cervical dystonia were enrolled in sequential cohorts to receive a single open‐label, intramuscular dose of injectable daxibotulinumtoxinA of up to 200 U (n = 12), 200–300 U (n = 12), or 300–450 U (n = 13; https://clinicaltrials.gov identifier NCT02706795).ResultsOverall, 33/37 enrollees completed the trial. DaxibotulinumtoxinA was associated with mean reductions in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)‐Total score of 16.8 (38%) at week 4, 21.3 (50%) at week 6, and 12.8 (30%) at week 24. The proportion of subjects who were responders (achieved ≥ 20% reduction in TWSTRS‐Total score) was 94% at week 6 and 68% at week 24. The median duration of response (time until > 20% of the improvement in TWSTRS‐Total score achieved at week 4 was no longer retained or re‐treatment was needed) was 25.3 weeks (95% CI, 20.14–26.14 weeks). There were no serious adverse events and there was no apparent dose‐related increase in the incidence of adverse events. The most common treatment‐related adverse events were dysphagia (14%) and injection site erythema (8%).ConclusionsPreliminary assessments suggest that injectable daxibotulinumtoxinA at doses up to 450 U is well tolerated and may offer prolonged efficacy in the treatment of cervical dystonia. Further studies involving larger numbers of patients are now warranted.

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“…A phase 2 open-label trial of daxibotulinumtoxinA in 33 patients with CD noted a mean duration of effect of 25.3 weeks, longer than typical effect durations of other BoNT-A formulations [34]. A similar prolonged effect was noted in another phase 2 trial examining its use in the treatment of glabellar lines [39]. These findings, however, must be confirmed by larger, phase 3 studies that are currently being conducted in multiple centers.…”

Section: Botulinum Toxin Structure and Functionmentioning

confidence: 91%

Immunogenicity Associated with Botulinum Toxin Treatment

Bellows

Jankovic

2019

Toxins

112

111

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Botulinum toxin (BoNT) has been used for the treatment of a variety of neurologic, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are currently in clinical use. While considered safe and effective, their use has been rarely complicated by the development of antibodies that reduce or negate their therapeutic effect. The presence of antibodies has been attributed to shorter dosing intervals (and booster injections), higher doses per injection cycle, and higher amounts of antigenic protein. Other factors contributing to the immunogenicity of BoNT include properties of each serotype, such as formulation, manufacturing, and storage of the toxin. Some newer formulations with purified core neurotoxin devoid of accessory proteins may have lower overall immunogenicity. Several assays are available for the detection of antibodies, including both structural assays such as ELISA and mouse-based bioassays, but there is no consistent correlation between these antibodies and clinical response. Prevention and treatment of antibody-associated non-responsiveness is challenging and primarily involves the use of less immunogenic formulations of BoNT, waiting for the spontaneous disappearance of the neutralizing antibody, and switching to an immunologically alternate type of BoNT.

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Injectable DaxibotulinumtoxinA for the Treatment of Glabellar Lines: A Phase 2, Randomized, Dose-Ranging, Double-Blind, Multicenter Comparison With OnabotulinumtoxinA and Placebo

Cited by 41 publications

References 4 publications

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications

Injectable DaxibotulinumtoxinA in Cervical Dystonia: A Phase 2 Dose‐Escalation Multicenter Study

Immunogenicity Associated with Botulinum Toxin Treatment

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