Evolus® Announces FDA Approval of EVOLYSSE™: HA Dermal Fillers

EVOLYSSE™: Why Next-Generation Dermal Fillers Matter for Your Medical Practice

The rising bar for “natural” outcomes

Patients arrive more informed than ever, comparing brands, technologies, and real-world outcomes before they book. They want subtle enhancement that preserves facial movement rather than a dramatic, static change. For clinics, that raises the bar: offer treatments that smooth and support while maintaining authentic animation—and do so within clear FDA labeling, transparent safety communication, and consistent technique. The newly FDA-approved EVOLYSSE™ line, which includes Evolysse™ Form and Evolysse™ Smooth, is indicated for the correction of moderate to severe dynamic facial wrinkles and folds (such as nasolabial folds) in adults 22 years or older, fitting squarely within this new generation of aesthetic solutions designed to maintain natural expression.

             Compliance note: This article focuses on EVOLYSSE™ Form and EVOLYSSE™ Smooth (FDA approval February 13, 2025). Any other EVOLYSSE™ variants are outside scope unless and until they receive FDA approval.

What has (and hasn’t) worked with traditional HA fillers

Early-generation HA fillers solved a major problem—volume and fold correction—but often forced trade-offs in tissue integration and movement in expressive areas (e.g., nasolabial folds). Practitioners sometimes described a choice between lift and natural feel, with degradation and palpability varying by product, technique, and patient factors. The manufacturing reality mattered: higher heat and certain crosslinking conditions can impact HA chain length and gel behavior, which in turn may influence how a filler molds, moves, and lasts.

Over the past several years, manufacturers have iterated on rheology, particle size, and crosslinking density. Yet many changes were incremental, not architectural. Clinicians have been waiting for a platform that aims to preserve more of HA’s native-like characteristics while still delivering on-label correction and predictable durability.

FDA approval: what’s actually authorized today

On February 13, 2025, the FDA approved EVOLYSSE™ Form and EVOLYSSE™ Smooth. Both products are indicated for dermal and subdermal injection to correct moderate to severe dynamic facial wrinkles and folds (such as nasolabial folds) in adults 22 years or older.

Details of this approval are available in the FDA Summary of Safety and Effectiveness Data (SSED) and in the product’s FDA-approved labeling, which document comparable safety and performance to the active control under study-defined parameters.
This serves as the regulatory reference standard for patient materials and professional communication.

The core idea behind Cold-X™ 

According to the manufacturer, Cold-X™ is a cold-temperature manufacturing approach designed to help preserve hyaluronic acid (HA) structure during processing and to achieve targeted rheological properties such as cohesivity and elasticity. This process minimizes thermal stress on the HA matrix during production.

Clinical outcomes vary by patient anatomy, injection technique, and treatment parameters.

Clinical program—what matters for everyday practice

The U.S. pivotal NLF studies were double-blind, randomized, split-face trials (n=140 across cohorts). Each subject served as their own control, receiving EVOLYSSE™ on one side and an FDA-approved comparator (Restylane®-L) on the other—an efficient way to reduce between-subject variability. Primary endpoints of non-inferiority were met for both Form and Smooth; Approval communications describe statistically significant differences at select time points within the pivotal studies, with a comparable safety profile (typical injection-site reactions; no treatment-related serious adverse events reported). These findings are study-specific and should not be generalized beyond the parameters of the clinical program., with a comparable safety profile (typical injection-site reactions; no treatment-related serious AEs were reported in the pivotal studies; as with HA fillers generally, rare events such as intravascular injection, ischemia/necrosis, or visual symptoms can occur.. Present these as study-specific findings—not universal superiority claims. 

Why split-face matters to you: it strengthens comparative interpretation for the on-label area (NLFs) while reminding us that real-world results vary with injector technique, volume, and patient metabolism.

How this translates to chairside choices

Form and Smooth share the platform but differ in viscoelastic behavior:

• EVOLYSSE™ Smooth — selected when refined smoothing and flexible movement are priorities along superficial-to-mid planes within the NLF trajectory.

• EVOLYSSE™ Form — selected where lift/support is needed in deeper dermal/subdermal planes along the NLF path, while maintaining pliability.

Match product to plane and purpose, stay within the FDA-approved indication, and follow the FDA-approved labeling/IFU for depth, device (needle/cannula), volume, and aftercare. Licensed, trained professionals only. 

Communicating benefits without overclaiming

Patients care about look, feel, and longevity—and so does your messaging:

• Look/feel: frame as design intent of Cold-X™ (not a guarantee). “Designed to look and feel natural in the skin.”

• Longevity: reference study follow-up (e.g., responders observed through 12 months in the SSED), but always include “individual results vary.” See FDA SSED and FDA-approved labeling for study details.

• Comparisons: if you mention statistically significant advantages vs. control, keep it study-specific, cite the FDA approval announcement/SSED, and avoid blanket superiority language.

Safety: the essentials to embed in workflow

Common reactions include tenderness, swelling, erythema, bruising, pain—usually mild/moderate and transient. As with any HA filler, be vigilant for intravascular events (blanching, disproportionate pain, visual symptoms). Use aseptic technique, inject slowly with minimal pressure, consider aspiration per local protocol and training, particularly near vascular landmarks, and provide clear aftercare with emergency contact instructions.. Delay treatment in infected or inflamed skin and exercise caution in patients on anticoagulants/antiplatelets.

Practical business impact—done compliantly

Why this matters to practice performance:

• Clinical alignment: A platform approved for the dynamic NLF area expands your on-label options without forcing a trade-off between support and animation—when appropriately selected and injected. See FDA SSED and FDA-approved labeling for study details.

• Operational clarity: Two products, one platform—simplifies staff education, consent language, and inventory compared with juggling unrelated systems.

• Patient retention: When results look subtle and authentic, satisfaction and word-of-mouth can improve—provided expectations are set accurately and follow-up is planned.

What about pipeline products?

You may see references to additional EVOLYSSE™ formulations under evaluation. As of this writing, only EVOLYSSE™ Form and Smooth are FDA-approved. Discussions of additional formulations should remain non-promotional until FDA decisions are final. Evolus has publicly discussed additional products (e.g., a mid-face volumizer under review), but those are not approved and must not be marketed for clinical use. Keep all pipeline mentions factual and non-promotional until FDA decisions are final.

Key takeaways for clinicians

• What’s approved: EVOLYSSE™ Form & EVOLYSSE™ Smooth (FDA approval Feb 13, 2025) for moderate to severe dynamic wrinkles/folds (such as NLFs) in adults 22+.

• What’s new: Cold-X™ Technology—a cold-temperature manufacturing approach designed to preserve HA structure and deliver gels designed to look and feel natural. Outcomes remain individual and technique-dependent.

• Evidence: Pivotal split-face trials met non-inferiority vs. an FDA-approved control; communications around the approval note statistically significant advantages at select timepoints with comparable safety. Keep claims study-specific.

• Safety: Typical HA filler AE profile; adhere to PI/IFU, injection best practices, and emergency readiness.

Important Safety Information 

Indication: EVOLYSSE™ Form and EVOLYSSE™ Smooth are indicated for dermal and subdermal injection to correct moderate to severe dynamic facial wrinkles and folds (such as nasolabial folds) in adults 22 years or older.

Contraindications/Precautions: Do not inject in areas of active inflammation or infection; use caution in patients with bleeding disorders or on anticoagulants/antiplatelets. Avoid in patients with known hypersensitivity to HA or lidocaine.

Adverse Reactions: Common reactions include tenderness, swelling, erythema, bruising, and pain at the injection site; typically mild to moderate and transient.
Use: For licensed, trained healthcare professionals only. Consult the full Prescribing Information and Instructions for Use.

Inside the Science and Clinical Program Behind EVOLYSSE™

Understanding the engineering behind Cold-X™ Technology

The approval of EVOLYSSE™ Form and EVOLYSSE™ Smooth reflects more than another filler launch — it marks a milestone in innovation under the Cold-X™ platform. EVOLYSSE™ Form and EVOLYSSE™ Smooth are FDA-approved. Discussions of additional formulations should remain non-promotional until FDA decisions are final.

Traditional filler manufacturing relies on heat and chemical catalysts to link HA chains into a stable gel. While effective for durability, those conditions can shorten polymer chains and alter rheology, potentially influencing elasticity and tissue integration.

Cold-X™ Technology, created by Symatese and licensed exclusively to Evolus®, uses controlled, low-temperature processing to help preserve the native configuration of hyaluronic acid. This method aims to:

• Maintain longer HA polymer segments for smoother gel texture.

• Enable precise crosslinking with minimal molecular fragmentation.

• Produce gels that balance stability and flexibility — essential in mobile facial zones.

• Preserve HA’s natural water-binding capacity, supporting even hydration within tissue.

In simple terms, Cold-X™ is engineered to retain more of HA’s original character while still delivering the resilience needed for clinical longevity. The result, in design intent, is a filler that is designed to look and feel natural while sustaining correction through months of facial motion. This technological premise differentiates EVOLYSSE™ from previous incremental updates in filler chemistry. 

Interpreting the clinical data with scientific balance

Evolus®’ pivotal nasolabial-fold (NLF) studies followed a double-blind, randomized, split-face design involving 140 adult participants. Each subject received EVOLYSSE™ on one side and an FDA-approved comparator (Restylane®-L) on the other, allowing each individual to serve as their own control.

Key outcomes reported in the FDA’s approval summary and Evolus®’ public communications include:

• Primary endpoint met — both Form and Smooth demonstrated non-inferiority to the comparator for wrinkle-severity improvement.

• Statistically significant advantages at specific evaluation points within the trial window.

• Sustained correction observed through 12 months, with responder rates maintained in a majority of subjects.

• Comparable safety profile, limited mainly to mild or moderate local reactions (tenderness, swelling, erythema, bruising). No treatment-related serious adverse events were recorded.

When communicating these findings to peers or patients, the phrasing should remain data-driven:

“In FDA-reviewed studies, EVOLYSSE™ Form and Smooth demonstrated correction of nasolabial folds through 12 months with a safety profile comparable to the control product; individual results vary.”

Distinct rheology for distinct clinical goals

Both EVOLYSSE™ formulations share the Cold-X™ base but differ in elastic modulus (G′) and viscosity (η*):

Product	Injection depth	Target concern	Rheology profile	Clinical intent
EVOLYSSE™ Smooth	Superficial-to-mid dermis	Fine-to-moderate wrinkles	Lower G′ for suppleness	Subtle correction with natural mobility
EVOLYSSE™ Form	Mid-to-deep dermis / subdermis	Moderate-to-severe folds	Higher G′ for lift and support	Structural correction with pliability

Both contain 0.3 % lidocaine to enhance patient comfort and are supplied in sterile prefilled syringes for single-patient use. Only licensed and appropriately trained healthcare professionals should administer these injectables, following the FDA-approval labeling and Instructions for Use (IFU).

Practical injection insights — clinical notes, not technique claims

Injectors experienced with mid-dermal HA gels will find EVOLYSSE™ handling familiar but not identical. Clinicians have reported smooth extrusion and cohesive spread; handling characteristics may vary by injector and tissue plane.

Recommended professional considerations include:

• Slow, incremental injection with constant visualization of tissue response.

• Aspiration as trained, particularly near vascular landmarks.

• Minimal over-correction; allow post-treatment hydration to contribute to final volume.

• Gentle molding immediately after placement, within the manufacturer’s recommended time window.

These are professional observations consistent with approved labeling and do not replace formal hands-on training. Evolus® provides injector education materials and emphasizes that outcomes depend on anatomy, technique, and experience.

Patient communication and expectation setting

Every consultation should balance enthusiasm for innovation with factual realism. Talking points that align with FDA language and fair-balance standard include:

• Design intent: “EVOLYSSE™ fillers are designed to look and feel natural in the skin.”

• Duration: “In clinical studies, improvement persisted through 12 months; however, individual results vary.”

• Safety: “Side effects are typically mild and temporary; serious complications are rare but require immediate medical attention.”

• Professional oversight: “These products should be injected only by licensed, trained providers familiar with facial anatomy.”

Framing expectations this way maintains transparency and positions the practitioner as a responsible expert rather than a salesperson.

Safety context — why balanced messaging matters

Like all injectable HA products, EVOLYSSE™ carries predictable, well-documented risks. The most common adverse reactions—tenderness, redness, swelling, bruising, pain, itching—usually resolve within a week. Rare events such as vascular occlusion or visual symptoms require immediate intervention with appropriate emergency protocols (e.g., hyaluronidase availability, ophthalmology referral).

Because EVOLYSSE™ is a new platform, regulatory-compliant communication requires that any safety discussion emphasize:

1. Known AE profile parallels existing HA fillers.

2. Serious complications, although uncommon, can occur.

3. Prompt recognition and treatment are critical.

4. Always follow the PI and established complication-management guidelines.

Embedding this information throughout the article—not just at the end—fulfills the “distributed safety” principle in medical-aesthetic communication.

1. Known AE profile parallels existing HA fillers.

2. Serious complications, although uncommon, can occur.

3. Prompt recognition and treatment are critical.

4. Always follow the PI and established complication-management guidelines.

Embedding this information throughout the article—not just at the end—fulfills the “distributed safety” principle in medical-aesthetic communication.

1. Known AE profile parallels existing HA fillers.

2. Serious complications, although uncommon, can occur.

3. Prompt recognition and treatment are critical.

4. Always follow the PI and established complication-management guidelines.

Embedding this information throughout the article—not just at the end—fulfills the “distributed safety” principle in medical-aesthetic communication.

Operational integration — simplifying procurement through Pipeline Medical

From a practice-management standpoint, access consistency matters as much as clinical performance. Pipeline Medical serves as a verified channel for EVOLYSSE™ distribution within the United States. Orders placed through the Pipeline marketplace are fulfilled through authorized distribution channels; maintain lot/expiry documentation and temperature-handling records per manufacturer requirements, ensuring product authenticity and compliance with manufacturer handling standards. 

Pipeline’s portal offers:

• Single-platform ordering for multiple vendors.

• Consolidated invoicing to reduce administrative workload.

• Dedicated support for product education and re-ordering.

No claims about temperature-control or exclusive rights are made; the messaging remains factual, echoing Pipeline’s public statements. This procurement model allows practices to streamline inventory while maintaining documentation accuracy—a regulatory expectation for prescription-device distribution.

Practice adoption checklist (compliant framework)

1. Clinical training — Ensure every injector reviews official Evolus® training and PI/IFU documents.

2. Informed consent — Update patient forms to specify EVOLYSSE™ Form or Smooth, indication, and potential AEs.

3. Inventory tracking — Document lot numbers and delivery confirmations through authorized portals.

4. Emergency readiness — Stock hyaluronidase and maintain vascular-event protocols.

5. Communication — Describe benefits in approved terms (“designed to feel natural,” “FDA-approved for NLF correction”), always coupling claims with variability statements.

Following this structure keeps promotional risk low and patient confidence high.

Clinical relevance beyond nasolabial folds

Use outside the FDA-approved indication (e.g., other facial areas) is considered off-label and requires documented informed consent, discussion of risks and alternatives, and conservative dosing within anatomic safety zones.

The FDA indication covers dynamic facial wrinkles and folds such as nasolabial folds in adults 22 years and older. Practitioners choosing to treat outside these approved areas should:

• Obtain separate informed consent for off-label areas.

• Avoid suggesting that efficacy or safety has been established for unapproved uses.

• Document rationale and patient agreement.

Summary of clinical and operational gains

• Regulatory validation: First FDA-approved cold-processed HA fillers in the U.S.

• Scientific differentiation: Cold-X™ preserves HA structure, aiming for authentic feel and flexibility.

• Evidence base: Pivotal split-face studies demonstrating on-label performance with comparable safety.

• Operational advantage: Reliable access via Pipeline Medical’s marketplace; direct shipping from Evolus®.

• Compliance alignment: All messaging grounded in FDA-approved labeling, avoiding therapeutic or superiority claims.

Integrating EVOLYSSE™ Into Practice and Preparing for the Future of Aesthetic Medicine

Translating Innovation Into Clinical Practice

With the FDA approval of EVOLYSSE™ Form and EVOLYSSE™ Smooth, medical professionals now have access to hyaluronic acid (HA) fillers designed with Cold-X™ Technology — a process intended to better preserve the HA molecular structure during manufacturing. In practice, these products allow FDA-approved correction of moderate-to-severe dynamic facial wrinkles and folds (such as nasolabial folds) in adults 22 years and older, using fillers engineered for balance between structure and movement.

Providers can now respond to patient demand for aesthetic results that feel natural and move authentically, while remaining within approved labeling and safety boundaries.

Why patient education matters now more than ever

Successful outcomes rely not only on the product and technique, but also on how clearly patients understand the treatment. Given how much patients research beforehand, explanations that build credibility and trust matter deeply.

When discussing EVOLYSSE™, clinicians should emphasize:

• FDA-Approved Indication: Only EVOLYSSE™ Form and EVOLYSSE™ Smooth are approved in the U.S., specifically for dynamic facial wrinkles and folds (e.g., nasolabial folds) in adults 22+.

• Design Intent: Cold-X™ Technology was developed to preserve the HA structure, producing gels designed to look and feel natural within the skin — a purposeful engineering choice, not a promise of outcome.

• Individual Variability: In clinical trials, correction was maintained through 12 months for many subjects — but results differ by anatomy, metabolism, and technique.

• Safety and Aftercare: Educate on expected side effects (redness, swelling, tenderness, bruising) and the importance of adhering to post-treatment instructions and reporting symptoms early.

This kind of balanced framing strengthens patient confidence and aligns with compliance expectations: no overpromise, full disclosure, and emphasis on individual results.

Incorporating EVOLYSSE™ into aesthetic workflows

Implementing a new filler line requires alignment across clinical, administrative, and marketing domains. The following steps help ensure smooth, compliant integration:

1. Clinical Training & Certification
   • All injectors should complete training provided by Evolus® or its authorized educators, focusing on rheology, Cold-X™ principles, and handling differences.

   • Review the full FDA-approval labeling and Instructions for Use (IFU) to understand injection depth, volume limits, and troubleshooting.

2. Consent & Documentation Updates
   • Revise consent forms to include EVOLYSSE™ product names, indication, common adverse events, and the possibility of variation in results.

   • Include a section about potential off-label use and clarify boundaries.

3. Inventory & Supply Management
   • Source EVOLYSSE™ exclusively via authorized channels, such as Pipeline Medical’s marketplace, where EVOLYSSE™ ships directly from Evolus® to ensure product authenticity and consistency.

   • Establish rigorous internal inventory-tracking protocols, including lot numbers and delivery logs.

4. Emergency Preparedness
   • Ensure hyaluronidase is readily available.

   • Practitioners must be well-versed in vascular occlusion protocols, early symptom recognition, and referral pathways.

5. Aligned Marketing & Communication
   • Promote EVOLYSSE™ using language consistent with FDA labeling (e.g., “FDA-approved for correction of moderate-to-severe dynamic facial wrinkles and folds in adults 22+”).

   • Avoid promotional superlatives like “best,” “longest-lasting,” or “clinically superior.” Stick to factual, data-supported statements with qualifiers like “designed to,” “in clinical studies,” and “individual results may vary.”

Ethical use and professional responsibility

While EVOLYSSE™ is approved for nasolabial folds and similar dynamic areas, any discussion of use in other facial zones (e.g., marionette lines, perioral areas) must be clearly identified as off-label. In such cases:

• Obtain explicit patient informed consent.

• Document the indication rationale, risk discussion, and expected behaviors.

• Avoid implying that off-label use is FDA-validated or supported by clinical trial data.

Role of Pipeline Medical as procurement partner

Procurement integrity is essential in aesthetic injectables. Pipeline Medical acts as a verified marketplace for EVOLYSSE™, offering:

• Direct shipping from Evolus®, which supports product authenticity and supply-chain traceability.

• A single-platform ordering interface that simplifies vendor management, inventory, and invoicing.

• Dedicated customer support to assist with order management and product information.

Describing Pipeline Medical in factual terms as a procurement facilitator (rather than a marketing entity) aligns with compliance and maintains corporate transparency.

Using EVOLYSSE™ for growth — ethically

EVOLYSSE™ helps meet patient expectations for natural movement, but true value lies in trust, retention, and reputation. Practices that emphasize transparent patient education, evidence-based discussions, and safe implementation can differentiate themselves in the market.

Key value levers include:

• Enhanced satisfaction when patients experience outcomes that feel authentic.

• Positioning as a clinic that embraces innovation responsibly.

• Reducing administrative burden through reliable procurement via Pipeline Medical.

• Strengthening credibility by always clarifying what is approved versus investigational.

Expert and branded perspectives (with attribution)

Evolus® has publicly described EVOLYSSE™ as a major technological advance in hyaluronic acid (HA) dermal fillers, reflecting the manufacturer’s perspective on innovation in aesthetics. This statement should not be interpreted as a clinical superiority claim. Similarly, executives reference Cold-X™ as a platform intended to preserve HA integrity and support expression-friendly outcomes.

When quoting manufacturer or executive statements, retain attribution and context. Emphasize that these are perspectives, not guaranteed claims.

Looking ahead: the future of Cold-X™ in filler science

EVOLYSSE™ Form and Smooth anchor Cold-X™ as a validated manufacturing platform. Additional formulations under development may expand the line as regulatory approvals permit. Any discussion of future or pipeline products should remain descriptive, avoid performance comparisons, and not imply availability until FDA clearance.

Evolution in filler science is incremental, but Cold-X™ signals a deeper shift in how HA gels might be engineered to favor integration and movement over rigidity.

Key professional takeaways

• FDA-approved products: EVOLYSSE™ Form & Smooth for dynamic wrinkles/folds (e.g., nasolabial folds) in adults 22+.

• Cold-X™ Technology: Designed to preserve HA structure and achieve balance between support and flexibility.

• Clinical evidence: In U.S. pivotal trials, these products met non-inferiority vs. comparator, with many maintaining improvement through 12 months; safety was comparable.

• Administration: Licensed, trained professionals only; use only by following the FDA-approval labeling and Instructions for Use (IFU)

• Procurement: EVOLYSSE™ is available through Pipeline Medical’s marketplace, with direct shipping from Evolus®.

• Communication guidance: Use approved claims, always include disclaimers (e.g., “individual results vary”), and avoid superlatives or therapeutic language.

Maintain fair-balance: present benefits with equal clarity on risks and limitations

Indication: EVOLYSSE™ Form and Smooth are indicated for dermal/subdermal injection to correct moderate-to-severe dynamic facial wrinkles and folds (such as nasolabial folds) in adults 22+.
Contraindications: Do not inject into areas of active infection or inflammation; avoid in patients with known hypersensitivity to HA or lidocaine.
Warnings: Risk of intravascular injection (embolization, ischemia); caution in patients with bleeding disorders or on anticoagulants.
Adverse Reactions: Most common: tenderness, redness, swelling, bruising, pain, itching. Usually mild and resolve within one week.
Use: For licensed, trained healthcare professionals only. Consult the full Prescribing Information and Instructions for Use for detailed guidance.

Safety in pregnancy or lactation has not been established; use only if benefits outweigh risks. Use caution in autoimmune disease, keloid tendency, or history of facial HSV. Do not mix in the same syringe with other products and avoid injecting over permanent fillers. Seek immediate care for blanching, severe/disproportionate pain, livedo, or vision changes.

Medical Disclaimer

The content herein is for educational purposes only and does not substitute for professional medical judgment. Clinicians should rely on their own experience and official product labeling when making treatment decisions.

Trademark Attribution

All product names and trademarks are the property of their respective owners. EVOLYSSE™ and Cold-X™ are trademarks of Evolus®, Inc.