Every botulinum toxin currently approved for aesthetic use in the United States arrives as a lyophilized (freeze-dried) powder that must be reconstituted with saline before injection. The reconstitution step introduces variability: how much saline, what technique, how long before the product degrades after mixing. RelabotulinumtoxinA (marketed internationally as Relfydess) is the first ready-to-use liquid neuromodulator — no reconstitution, no preparation, drawn directly from the vial.
On February 2, 2026, Galderma announced that the FDA had accepted the resubmission of its Biologics License Application (BLA) for relabotulinumtoxinA, seeking approval for the temporary improvement of moderate-to-severe glabellar lines (frown lines) and lateral canthal lines (crow's feet) in adults. The acceptance follows a 2023 CRL that was limited to Chemistry, Manufacturing, and Controls (CMC) issues; no safety or efficacy deficiencies were identified in the original review.
Relfydess is already approved in over 20 markets, including the European Union, the United Kingdom, Australia, and several countries in Asia. US approval, if granted, would make it the seventh neuromodulator available domestically — and the first with a liquid formulation.
This article breaks down the clinical evidence, the formulation technology, the regulatory timeline, and what Relfydess's profile means for patients and providers.
PEARL Technology and why liquid formulation matters
Relfydess is manufactured using Galderma's proprietary PEARL Technology, designed to preserve the structural integrity of the botulinum toxin molecule in a liquid state. Botulinum toxin type A is a protein complex that is sensitive to denaturation — the reason all current products are freeze-dried for stability and reconstituted at the point of care.
The practical implications of a ready-to-use liquid formulation:
- No reconstitution variability. Every vial delivers the same concentration. There is no risk of over- or under-dilution, which can affect both efficacy and the spread of the product beyond the target muscle.
- Volumetric dosing. Providers draw a specified volume rather than calculating unit-to-saline ratios. The recommended dose for glabellar lines is 50 units in a fixed volume, injected in five standardized points.
- No cold-chain preparation step. Lyophilized products must be stored at specific temperatures and mixed carefully to avoid agitation-induced degradation. A liquid product eliminates the preparation step, though cold storage is still required.
- Time efficiency. Eliminating reconstitution saves several minutes per patient visit. In high-volume practices, this compounds into meaningful time savings across a day.
The elimination of reconstitution is not a clinical breakthrough — it does not make the toxin work better. But it is a workflow and consistency improvement that matters to providers who treat dozens of patients per day.
The READY clinical program: four Phase 3 trials, 1,900+ participants
The BLA is supported by the READY (REelabotulinumtoxin Aesthetic Development StudY) clinical program, comprising four Phase 3 trials:
| Study | Design | Indication | Patients |
|---|---|---|---|
| READY-1 | Double-blind, randomized, placebo-controlled | Glabellar lines | ~450 |
| READY-2 | Double-blind, randomized, placebo-controlled | Lateral canthal lines | — |
| READY-3 | Double-blind, randomized, placebo-controlled | Glabellar lines + lateral canthal lines (combination) | — |
| READY-4 | Open-label, long-term safety | Glabellar lines + lateral canthal lines, repeated dosing over 12 months | — |
Total enrollment across the four trials exceeded 1,900 participants.
Onset and duration
Results from the READY program demonstrated:
- Onset as early as Day 1. Approximately 39% of patients showed visible improvement within 24 hours of treatment. This is faster than most serotype A products, where onset typically ranges from 2–5 days, though Dysport has reported similar day-1 onset rates.
- Sustained efficacy up to 6 months. Up to 75% of treated patients had not returned to baseline at the 6-month mark. This positions Relfydess in a similar duration tier to Botox and Dysport (3–4 months typical, up to 6 months for some patients), rather than competing with Daxxify's claim of 5–6 month median duration.
- Consistent results across severity levels. Subgroup analyses presented at TOXINS 2026 in Madrid (January 2026) showed that efficacy outcomes were consistent across patients with moderate and severe baseline wrinkle severity for both glabellar lines and lateral canthal lines.
Dual indication: glabellar lines and crow's feet
If approved, Relfydess would be the first neuromodulator to launch in the US with simultaneous approval for both glabellar lines and lateral canthal lines. Current products received their crow's feet indications sequentially — Botox Cosmetic received its lateral canthal line approval in 2013, 11 years after its initial glabellar line approval.
The dual indication matters because it reflects the way the product was studied: patients in READY-3 received simultaneous treatment of both areas, and the safety data support combined use in a single visit.
Safety profile
Treatment-related adverse events across the READY program were consistent with the known profile of botulinum toxin type A products:
- Treatment-related treatment-emergent adverse events were reported by 18% of participants in READY-4, all considered mild to moderate in severity.
- Eyelid ptosis rates were comparable to established neuromodulators — an important finding because ptosis is one of the most visible and patient-impactful adverse events in upper-face neuromodulator treatment.
- An in vivo head-to-head diffusion study comparing relabotulinumtoxinA with onabotulinumtoxinA (Botox) in a rat model showed similar and limited diffusion profiles. This addresses a common clinical concern: that a liquid formulation might spread more broadly from the injection site, increasing the risk of unintended muscle weakness in adjacent areas.
The regulatory timeline
First CRL (2023)
The FDA issued a Complete Response Letter for relabotulinumtoxinA in 2023. The CRL cited deficiencies limited to Chemistry, Manufacturing, and Controls (CMC) processes. No safety or efficacy concerns were identified, and no additional clinical studies were requested.
The CMC issues likely related to the novel manufacturing process for the liquid formulation — a process that has no precedent in the FDA's regulatory experience with botulinum toxins, since all prior products are lyophilized. CMC CRLs for novel formulations are common; the agency needs to validate that the manufacturing process consistently produces a stable, potent product.
BLA resubmission (February 2026)
Galderma resubmitted the BLA after working with the FDA to implement manufacturing process adjustments. The FDA accepted the resubmission on February 2, 2026, indicating that the application is sufficiently complete for substantive review.
The review timeline depends on whether the FDA classifies the resubmission as Class 1 (typically a 2-month review) or Class 2 (6-month review). Given that the CMC issues were the sole deficiency and Galderma has had over two years to address them, a Class 1 classification is plausible but not guaranteed.
A reasonable estimated timeline for potential US approval is mid-to-late 2026.
International approvals
Relfydess has received marketing authorization in over 20 markets. The European Commission granted approval in 2024 following a positive opinion from the decentralized procedure. Australia approved the product in July 2024. Regulatory applications continue in additional markets globally.
How Relfydess fits in the neuromodulator landscape
If approved, Relfydess would enter a US market with six competing serotype A products:
| Product | Sponsor | Key differentiator | Duration (approx.) |
|---|---|---|---|
| Botox Cosmetic | AbbVie/Allergan | Market leader, longest track record | 3–4 months |
| Dysport | Galderma | Fast onset, established diffusion profile | 3–4 months |
| Xeomin | Merz | No accessory proteins (naked toxin) | 3–4 months |
| Jeuveau | Evolus | Price-competitive positioning | 3–4 months |
| Daxxify | Revance | Longest duration (peptide excipient) | 5–6 months |
| Letybo | Hugel | Most recent approval (2024) | 3–4 months |
| Relfydess | Galderma | Liquid formulation, no reconstitution, dual indication | Up to 6 months |
Galderma would become the only company with two neuromodulators on the US market — Dysport and Relfydess. The portfolio strategy appears designed to offer providers a choice within the Galderma ecosystem: Dysport for practices comfortable with reconstitution and established protocols, Relfydess for practices that value convenience and the dual-indication label.
Relfydess is not the only product approaching FDA review. AbbVie's trenibotulinumtoxinE (TrenibotE), a serotype E neuromodulator with an 8-hour onset and 2–3 week duration, received a CRL in April 2026 for manufacturing issues. If both products are eventually approved, the US neuromodulator market could expand from six to eight products within a 12–18 month window.
What patients should know
Relfydess is not approved in the United States as of June 2026. It is available in the EU, UK, Australia, and select Asian markets under the brand name Relfydess.
If approved, patients should understand:
- Liquid formulation does not change the fundamental mechanism. Relfydess is still a botulinum toxin type A that works by temporarily reducing muscle activity. The liquid formulation affects convenience and consistency, not how the product works in the body.
- Dual indication means both frown lines and crow's feet were studied. Treating both areas in a single session is supported by the clinical data, but any provider treating lateral canthal lines should have specific training in periorbital anatomy — regardless of which product is used.
- Duration claims are averages, not guarantees. "Up to 6 months" means some patients in the trials maintained results that long; individual results will vary based on dose, anatomy, metabolism, and treatment area.
- Reconstitution-free does not mean risk-free. All botulinum toxin products carry the same core risks: ptosis, asymmetry, bruising, headache, and — rarely — systemic effects. The adverse-event profile in the READY trials was consistent with established products.
What providers should know
- Volumetric dosing simplifies training but requires protocol discipline. The elimination of reconstitution math is a workflow win, but providers still need to understand anatomy, injection depth, and dose per site. Convenience does not compensate for poor technique.
- The dual indication label could differentiate practices. If Relfydess is the only product explicitly labeled for simultaneous glabellar and lateral canthal line treatment at launch, practices can market combined upper-face treatments with labeling support that competitors lack.
- Diffusion data are reassuring but preclinical. The in vivo diffusion study showed similar spread to onabotulinumtoxinA in a rat model. Human clinical diffusion characteristics will become clearer with real-world use.
- Pricing has not been announced. The value proposition of a ready-to-use liquid depends on whether the convenience premium is absorbed by the practice, passed to the patient, or shared.
Sources
- Galderma. Galderma Announces U.S. FDA Acceptance of RelabotulinumtoxinA Biologics License Application Resubmission. Business Wire, February 2, 2026. https://finance.yahoo.com/news/galderma-announces-u-fda-acceptance-060000079.html
- Galderma. TOXINS 2026: Clinical Updates on Galderma's Leading Neuromodulator Portfolio Further Reinforce Its Leadership in Injectable Aesthetics. Business Wire, January 2026. https://www.businesswire.com/news/home/20260113854672/en/TOXINS-2026-Clinical-Updates-on-Galdermas-Leading-Neuromodulator-Portfolio-Further-Reinforce-Its-Leadership-in-Injectable-Aesthetics
- Shridharani SM, et al. Efficacy and safety of RelabotulinumtoxinA, a new ready-to-use liquid formulation botulinum toxin: Results from the READY-1 phase 3 trial in glabellar lines. Aesthet Surg J. 2024;44(12):1330-1340. doi:10.1093/asj/sjae131. PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623810
- Ablon G, et al. Treatment of lateral canthal lines with RelabotulinumtoxinA: clinical efficacy and safety results from the READY-2 phase 3 trial. Toxicon. 2024;237(1):107353. doi:10.1016/j.toxicon.2024.107353
- Ablon G, et al. RelaBoNT-A Treatment of Glabellar Lines and Lateral Canthal Lines of Different Baseline Severity: Subgroup Analyses. Abstract #0080, TOXINS 2026, Madrid.
- Relfydess (relabotulinumtoxinA) Australian Product Information. Galderma. July 2024. https://www.galderma.com/au/sites/default/files/Relyfdess_PI_ApprovedJuly2024.pdf
- Dermatology Times. Galderma Presents Phase 3 Relfydess Data and Dysport Innovations at TOXINS 2026. https://www.dermatologytimes.com/view/galderma-presents-phase-3-relfydess-data-and-dysport-innovations-at-toxins-2026
- AmSpa. Galderma's RelabotulinumtoxinA Moves Closer to U.S. Market After FDA Accepts BLA Resubmission. February 5, 2026. https://www.americanmedspa.org/news/galdermas-relabotulinumtoxina-moves-closer-to-u-s-market-after-fda-accepts-bla-resubmission
- Clinical Trials Arena. Galderma reports data from Phase III trial for RelabotulinumtoxinA. https://www.clinicaltrialsarena.com/news/galderma-reports-data-trial
