Hyaluronic Acid Derivatives Clinical Policy Form

PREFERRED: Durolane and Visco-3; then Euflexxa, and Gelsyn-3 • J7318 Hyaluronan or derivative, Durolane, for intra-articular injection, per dose • J7321 Hyaluronan or derivative, Visco-3, for intra-articular injection, per dose (Hyalgan and Supartz are non-preferred) • J7323 Hyaluronan or derivative, Euflexxa, for intra-articular injection, per dose • J7328 Hyaluronan or derivative, Gelsyn-3 for intra-articular injection, 0.1 mg PART B DRUG MEDICAL/PHARMACY Effective Date April 1, 2025 Policy # HYALURONIC ACID, VISCOSUPPLEMENTATION: DUROLANE®, EUFLEXXA™, GEL-ONE®, GELSYN-3™, GENVISC 850®, HYALGAN™, HYMOVIS®, MONOVISC® , ORTHOVISC™, SUPARTZ /, SYNOJOYNT, SYNVISC™, SYNVISC- ONE™, TRILURON™, TRIVISC™, VISCO-3™, & SODIUM HYALURONATE 1% Hyaluronic Acid Review Date Applicable to: 02/25/2025 Medicare Advantage Commercial Elevance Health HMO Blue Shield Trio Approver’s Name & Title QI & UM Drug Subcommittee Aspire Health Plan applies medical drug clinical criteria as a reference for medical policy information only. Federal and state laws or requirements, contract language, and Plan benefit may take precedence over the application of these clinical criteria. Please consult the applicable certificate or contract for benefit details. This policy is subject to revision at the discretion of the Plan and is therefore subject to change. Refer to the ‘Disclaimer’ section below for more information. POLICY This policy outlines the coverage criteria for hyaluronan preparations (viscosupplementation) used for intra-articular injections of the knee. Available Hyaluronan (HA) Agents: Multiple HA producats are available, differing in molecular weights and the number of injections required per treatment course. Some products are administeres as a single injection. While others require 3 to 5 injections per course. For additional information on dosage, administration, and product-specific information, refer to:
• The ‘Dosage and Administration’ table in this policy. • The prescribing information for each individual product. APPLICABLE HCPCS NON-PREFERRED • J7320 Hyaluronan or derivative, GenVisc 850, for intra-articular injection, 1 mg • J7321 Hyaluronan or derivative, Hyalgan and Supartz for intra-articular injection, per dose

(Visco-3 is preferred) • J7322 Hyaluronan or derivative, Hymovis, for intra-articular injection, 1 mg
• J7324 Hyaluronan or derivative, Orthovisc, for intra-articular injection, per dose • J7325 Hyaluronan or derivative, Synvisc or Synvisc-One, for intra-articular injection, 1 mg J7326 Hyaluronan or derivative, Gel-One, for intra-articular injection, per dose • J7327 Hyaluronan or derivative, Monovisc, for intra-articular injection, per dose • J7329 Hyaluronan or derivative, TriVisc, for intra-articular injection, 1 mg
• J7331 Hyaluronan or derivative, Synojoynt, for intra-articular injection, 1 mg
• J7332 Hyaluronan or derivative, Triluron, for intra-articular injection, 1 mg CLINICAL CRITERIA A. INITIAL CRITERIA

Intra-articular Hyaluronic Acid products may be authorized when ALL of the following criteria are met with documentation:

1. Diagnosis: Documented diagnosis of osteoarthritis of the knee; AND

2. Affected Knee(s): Documentation specifying the affected knee(s): Left, right or bilateral.
   NOTE: Bilateral injections may be allowed only if both knees meet criteria.

   AND

3. Pain and Functional Limitation: Documentation of knee pain that significantly interferes with functional activities (e.g., ambulation, prolonged standing, stair climbing, activities of daily living). Quantifiable pain scales (e.g., VAS, NRS) and/or functional assessments (e.g., WOMAC, KOOS) are recommended.

   AND

4. Conservative Therapy Trial: Documentation of a minimum of 3 months of conservative therapy, including both non-pharmacologic and pharmacologic approaches, unless contraindicated:

   a. Non-pharmacologic Therapy: Examples include (but are not limited to): physical therapy, exercise programs, weight management, self-management programs, knee brace, cane. b. Pharmacologic Therapy: Examples include (but are not limited to): acetaminophen, oral and/or topical nonsteroidal anti-inflammatory drugs (NSAIDs), and topical capsaicin.

   AND

5. Prior Intra-articular Corticosteroid Injection: Documentation of failure of, or contraindication to, at least one intra-articular glucocorticoid injection; AND

6. Contraindications: Absence of any contraindications to HA injections, including active joint infection, skin infection at the injection site, known hypersensitivity to HA products, or other conditions that would preclude intra-articular injections (e.g., unstable joint, bleeding disorders, etc.); AND

7. Prescriber specialty Administered by, or under the supervision of, a physician (MD or DO) specializing in rheumatology, orthopedic surgery, or physical medicine and rehabilitation (physiatrist), or a physician with documented training and experience in the administration of viscosupplements; AND

8. For non-preferred hyaluronic acid intra-articular injections: Refer to Step Therapy Requirements.

   B. REAUTHORIZATION / CONTINUATION OF THERAPY CRITERIA

   Hyaluronic Acid products may be authorized for continuation of therapy when initial criteria have been met AND there is documentation of beneficial response from previous course of treatment:

9. Time Interval: At least six (6) months have lapsed since the completion of the prior HA treatment course.

10. Demonstrated Benefit: Documentation of beneficial response from the previous HA treatment course, including improvement in pain, function, and/or other relevant clinical outcomes. Quantifiable measures (e.g., pain scales, functional assessments) are strongly recommended; AND

11. Absence of Adverse Events: Documentation of the absence of unacceptable adverse events or toxicity from the previous HA injections. This includes, but not limited to, severe joint swelling, pain, severe pain, infection, or hypersensitivity reactions.

    STEP THERAPY

    Step Therapy Does NOT Apply if: • The member is currently being treated with the requested medication. • The member has received the requested drug within the last 365 days.

    Step Therapy Applies if: • The member is new to therapy (i.e., has not received the requested drug in the last 365 days). A. PREFERRED PRODUCT(S): Durolane and Visco-3; then Euflexxa, and Gelsyn-3 (no step therapy required)

    B. NON-PREFERRED hyaluronic products may be authorized when ALL of the clinical criteria above are met AND the member meets the following criteria for a non-preferred product:

12. Documented history of intolerance or adverse event(s) to the following PREFERRED products unless contraindicated: Durolane and Visco-3.

    NOTE: For members with allergies to avian proteins and products (e.g., eggs, feathers): Preferred products are Euflexxa, Gel-Syn-3.

    OR

13. Member has previously received the requested brand of hyaluronic product within the past 365 days and therefore not subject to step therapy requirements.

DRUG INFORMATION

PHARMACOLOGIC CATEGORY: Antirheumatic Miscellaneous

ROUTE OF ADMINISTRATION: Intra-articular injection into the knee joint

FDA-APPROVED INDICATIONS: • Osteoarthritis of the knee: Hyaluronic acid (HA) injections are indicated for the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative non-pharmacologic therapy and simple analgesics (e.g., acetaminophen) or nonsteroidal anti-inflammatory drugs (NSAIDs).

COMPENDIAL APPROVED (OFF-LABEL) USES: None

CONTRAINDICATIONS:
• Hypersensitivity to hyaluronate or any component of the formulation.
• Known hypersensitivity to gram-positive bacterial proteins (applies to Hymovis, Monovisc and Orthovisc only).
• Knee joint infections, infections, or skin diseases in the area of the injection site or joint.
• Known systemic bleeding disorders (applies to Monovisc only).

DOSAGE AND AUTHORIZATION TIMEFRAMES

1. Recommended Dosage: HA product dosage and administration frequency must strictly adhere to the FDA-approved labeling for the specific product being used. Do not exceed the recommended dosage or frequency outlined in the product's labeling.

   Maximum Dose: One treatment course per joint every 6 months. Dose and frequency should be in accordance with the FDA label or *CMS-recognized compendia.

   *The CMS-approved authoritative compendia are listed in the CMS Internet Only Manual (IOM) Publication 100-02, Medicare Benefit Policy Manual, Chapter 15, Section 50.4.5 AHFS DI; Clinical Pharmacology; DRUGDEX; Lexi-Drugs; and NCCN Compendium may be used to support clinical decision-making when the FDA label allows for flexibility. However, these compendia do not establish coverage policy. Coverage decisions are based on the totality of the clinical evidence and applicable guidelines.

2. Authorization Period: Re-authorization is required every 12 months to determine effectiveness of therapy and continued need based criteria stated in the ‘Continuation of Therapy’ section.

   RECOMMENDED DOSAGE Drug HCPCS Number of Administration (per knee per 180 days) Max Units (per 180 days)Max units are based on administration to both knees 1 Billable Unit (BU) BU per Admin Durolane J7318 1 injection 120 1 mg 60 Euflexxa J7323 3 injections 6 1 dose 1 Gel-One J7326 1 injection 2 1 dose 1 GelSyn-3 J7328 3 injections 1008 0.1 mg 168

GenVisc 850 J7320 5 injections 250 1 mg 25 Hyalgan; Supartz J7321 5 injections 10 1 dose 1 Hymovis J7322 2 injections 96 1 mg 24 Monovisc J7327 1 injection 2 1 dose 1 Orthovisc J7324 4 injections 8 1 dose 1 sodium hyaluronate J7331 3 injections 120 1 mg 20 Synojoynt J7331 3 injections 120 1 mg 20 Synvisc J7325 3 injections 96 1 mg 16 Synvisc-One J7325 1 injections 96 1 mg 48 Triluron J7332 3 injections 120 1 mg 20 TriVisc J7329 3 injections 150 1 mg 25 VISCO-3 J7321 3 injections 6 1 dose 1

CLINICAL SUMMARY / APPENDIX Professional Society Guidelines on Hyaluronic Acid Injections for Knee Osteoarthritis (OA): Recommendations for the use of intra-articular hyaluronic acid (HA) injections varies among professional society. Key guidelines include: 1. American College of Rheumatology (ACR 2020) • Recommend against the use of intra-articular HA injections for knee OA. • Notes that when trials with high-risk-of-bias are excluded, HA does not provide a meaningful benefit. The overall quality of the evidence is low, and recommendations are conditional or moderate. Shared decision-making, considering patient values is appropriate. 2. American Academy of Orthopaedic Surgeons (AAOS 2021) • Recommends against the routine use of intra-articular HA injections for symptomatic knee OA. 3. Osteoarthritis Research Society International (OARSI 2019) • Recommends considering intra-articular HA injections for all patients with knee OA (OARSI 2019). 4. National Institute for Health and Care Excellence (NICE 2022, NG226) • Recommends against offering intra-articular HA injections for knee OA REFERENCES Government Agency Centers for Medicare and Medicaid Services (CMS). Medicare coverage database (no National Coverage Determination identified; no LCDs available for local MAC). Available from CMS. Prescribing Information 1. Durolane (sodium hyaluronate) [prescribing information]. Durham, NC: Bioventus LLC; September 2019. 2. Euflexxa [prescribing information]. Parsippany, NJ: Ferring Pharmaceuticals Inc; July 2016. 3. Hyalgan (hyaluronic acid derivative) [prescribing information]. Parsippany, NJ: Fidia Pharma; August 2017. 4. Hymovis (hyaluronic acid derivative) [prescribing information]. Parsippany, NJ: Fidia Pharma; June 2021. 5. Gelsyn-3 (sodium hyaluronate) [prescribing information]. Durham, NC: Bioventus; September 2019. 6. Gel-One (cross-linked hyaluronate) [prescribing information]. Warsaw, IN; Zimmer; August 2018. 7. GenVisc 850 (sodium hyaluronate) [prescribing information]. Doylestown, PA: OrthogenRx Inc; November 2019. 8. Monovisc [prescribing information]. Bedford, MA: Anika Therapeutics; July 2020. 9. Sodium hyaluronate [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; March 2019.

10. Synojoynt [package insert]. Naples, FL; Arthrex, Inc.; January 2022.
11. Synvisc (hylan G-F 20) [prescribing information]. Ridgefield, NJ: Genzyme Biosurgery; May 2023.
12. Synvisc One (hylan G-F 20) [prescribing information]. Ridgefield, NJ: Genzyme Biosurgery a division of Genzyme Corporation; May 2023.
13. TriVisc (sodium hyaluronate) [prescribing information]. Doylestown, Pennsylvania: OrthogenRx Inc; November 2019
14. Triluron (sodium hyaluronate) [prescribing information]. Florham Park, NJ: Fidia Pharma USA Inc;

July 2019.

15. Visco-3 (sodium hyaluronate) [prescribing information]. Warsaw, IN: Zimmer; received April 2017. Peer-reviewed Literature, Guidelines, Consensus 1. American Academy of Orthopaedic Surgeons Management of Osteoarthritis of the Knee (NonArthroplasty) Evidence-Based Clinical Practice Guideline. https://www.aaos.org/oak3cpg Published 08/31/2021. 2. Brophy RH, Fillingham YA. AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition. AAOS 2021 Aug 31 PDF 3. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 Jun;27(11):1578-1589. DOI:https://doi.org/10.1016/j.joca.2019.06.011. 4. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee Arthritis Rheumatol. 2020 Feb;72(2):220-233. doi: 10.1002/art.41142. Epub 2020 Jan 6. 5. National Institute for Health and Care Excellence (NICE) NICE guideline (NG226) Osteoarthritis in over 16s: diagnosis and management. Published: 19 October 2022, https://www.nice.org.uk/guidance/ng226. IMPORTANT REMINDER This Medicare Part B Step Therapy Medical Necessity Guideline is for informational purposes only and does not constitute or replace professional medical advice. Physicians, hospitals, and other providers are responsible for administering and using drugs/biologicals in the most effective and clinically appropriate manner and are solely responsible for all medical care decisions. This guideline is not a substitute for clinical judgment or individualized patient care. Coverage determinations are based on the member's Evidence of Coverage (EOC), which contains specific coverage provisions, limitations, and exclusions. In the event of a conflict between this guideline and the member's EOC, the EOC will govern. Aspire Health Plan (AHP) adheres to applicable Medicare guidelines, including National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs), and other relevant Medicare manuals published by the Centers for Medicare & Medicaid Services (CMS). Compliance with these guidelines is required where applicable. For the most current Medicare policies and coverage information, please refer to the CMS website at cms.gov and search the Medicare Coverage Database. All LCDs are the same for each state within a Jurisdiction. The Medicare Administrative Contractor (MAC) for California (Jurisdiction E) is Noridian. Active LCDs for JE Part B can be found on the Noridian Medicare website (noridianmedicare.com). In the event of a discrepancy between this guideline and a Medicare NCD or LCD, the NCD/LCD will govern. This guideline is used by AHP to determine coverage in the absence of applicable CMS Medicare guidelines. The Medicare source materials used to develop this guideline are referenced below. This document does not replace the official Medicare source materials, which provide detailed information on Medicare coverage requirements. In the event of a conflict between this document and Medicare source materials, the Medicare source materials will prevail. The inclusion of a code in this guideline does not guarantee coverage or reimbursement. Benefit coverage is determined by the member's specific plan document, applicable state and federal laws, and CMS guidelines. Inclusion of a code does not imply or guarantee payment. Other policies and standards may also apply. Providers are expected to maintain documentation to support coverage decisions and make it available upon request.

AHP-Hyaluronic Acid, Viscosupplementation POLICY HISTORY Version Approval Date Summary of Changes 1 9/27/2023 New Policy 2 02/25/2025 Annual Review. The policy has been revised and reformatted to enhance clarity with no alteration to the intent or clinical criteria. References reviewed and policy updated where applicable. Effective 05/15/2025.