Herceptin biosimilars compared: FDA status, payer coverage, coding, and switching for trastuzumab

Herceptin (trastuzumab, Genentech/Roche) was the first HER2-targeted monoclonal antibody, transforming treatment of HER2-positive breast and gastric cancers. US biosimilar entry began in 2019, and six biosimilars are now FDA-approved. None carry the interchangeable designation, meaning pharmacy-level substitution is not available and prescriber intent is required. Payers and health systems have nonetheless moved to prefer biosimilars over branded Herceptin for cost reasons.

This reference-product dossier is for oncologists, oncology pharmacists, access teams, and payer professionals who need to track which trastuzumab biosimilars are available, how payers are covering them, and what operational rules apply.

FDA-approved biosimilars

As of May 2026, six biosimilars referencing Herceptin have been approved by the FDA:

Interchangeability

None of the six biosimilars carry the FDA interchangeable designation. All are approved as biosimilars only. This means they cannot be automatically substituted for Herceptin at the pharmacy level and must be specifically prescribed or ordered. In practice, oncology biologics are typically administered in clinical settings under buy-and-bill reimbursement, so interchangeability designation has less operational impact than it does for pharmacy-benefit drugs like Humira.

Indications

All six biosimilars share the same FDA-approved indications as Herceptin:

• Adjuvant breast cancer (HER2-positive)
• Metastatic breast cancer (HER2-positive)
• Metastatic gastric or gastroesophageal junction adenocarcinoma (HER2-positive)

NCCN guidelines note that an FDA-approved biosimilar is an appropriate substitute for the reference product in HER2-positive disease.

Formulations and devices

Trastuzumab products are administered by intravenous infusion. Key differences:

• Herceptin: Available as a single-dose vial (150 mg, 420 mg multi-dose vial discontinued). Also available as Herceptin Hylecta (trastuzumab and hyaluronidase-oysk), a subcutaneous injection with a different HCPCS code (J9356).
• Biosimilars: Available in both single-dose vials (150 mg) and multi-dose vials (420 mg). Product availability varies by manufacturer.
• Hercessi: Available in 150 mg single-dose vial and 420 mg multi-dose vial.

HCPCS coding and billing

Trastuzumab products are reimbursed under Medicare Part B (medical benefit) using buy-and-bill. The HCPCS codes are:

Note: Unbranded trastuzumab-pkrb (the unbranded biologic of Herzuma) also uses Q5113. J9355 is specific to branded Herceptin and excludes biosimilars. The JW modifier (amount discarded) is allowed for Herceptin (single-dose vial only) but is not allowed for biosimilars approved based on multi-dose vial use.

Payer and health system coverage

Commercial insurance

Payers routinely prefer biosimilar trastuzumab over branded Herceptin. Step-therapy and prior authorization protocols typically require a trial of a preferred biosimilar before Herceptin is covered:

• Community Health Choice: Kanjinti, Ogivri, Ontruzant, Herzuma, and Trazimera are preferred. Herceptin requires prior authorization and documented trial or intolerance to preferred biosimilars.
• Anthem/Elevance Health (now Elevance): Similar structure — biosimilars preferred, Herceptin requires step therapy through a biosimilar first.
• Aetna: Covers all trastuzumab products with prior authorization. Herceptin is covered when criteria are met, but biosimilars are listed without step-therapy restrictions in many policy configurations.
• Mass General Brigham Health Plan: Preferred products include Kanjinti, Ogivri, and Ontruzant. Herceptin requires documented inadequate response or intolerance to preferred biosimilars.
• Prime Therapeutics: Manages medical-necessity criteria for trastuzumab products across multiple Blue Cross Blue Shield plans. Preferred biosimilars are listed without additional step-therapy barriers.
• FEP Blue (Federal Employee Program): Preferred products are Kanjinti, Ogivri, and Ontruzant.

Medicare Part B

Trastuzumab is covered under Medicare Part B when administered in a clinical setting. Medicare reimburses biosimilars at the biosimilar average sales price (ASP) plus 6%, compared to the reference product ASP plus 6% for branded Herceptin. The ASP for biosimilars is generally lower, which reduces both the reimbursement amount and the patient's 20% coinsurance obligation.

340B and hospital formulary

Hospital systems and academic medical centers have been shifting utilization to biosimilars, particularly in the 340B setting where the spread between acquisition cost and reimbursement is favorable. Formulary decisions often come down to:

• Which biosimilar has the most favorable contract pricing
• Multi-dose vial availability (reduces waste and cost per dose)
• Prior authorization requirements specific to the payer mix

What changed recently

• Hercessi approval (April 2024): The sixth trastuzumab biosimilar, manufactured by Accord BioPharma, received FDA approval and launched in July 2024. Payer policies have been updated to include Hercessi alongside the other five biosimilars.
• Pipeline entrants still pending: Tanvex (TX05) received a Complete Response Letter in January 2025. EirGenix/Sandoz (EG12014) resubmitted its BLA in June 2025. These could add further competition and price pressure if approved.
• Ogivri label update: Biocon Biologics/Viatris updated the Ogivri prescribing information in November 2024.
• Hercessi coding: HCPCS code Q5146 was established for Hercessi, assigned by CMS for billing effective 2024.

What to monitor next

• Additional biosimilar approvals: The Tanvex and EirGenix/Sandoz trastuzumab BLAs remain active. Approval of additional products could further erode Herceptin's remaining market share and drive ASP convergence.
• Payer exclusions of branded Herceptin: As more payers move to biosimilar-preferred or biosimilar-only formularies for trastuzumab, monitor whether any major commercial plans or PBMs issue explicit exclusion notices similar to those seen with Humira.
• Subcutaneous trastuzumab competition: Herceptin Hylecta (subcutaneous) is not currently facing biosimilar competition. If a subcutaneous trastuzumab biosimilar is developed, it would change the administration and site-of-care calculus.
• Medicare Part B biosimilar add-on payment: Congress has periodically considered changes to the biosimilar reimbursement formula. Monitor CMS rulemaking for any adjustments to the ASP+6% add-on that could affect the financial incentive to use biosimilars.
• ADC and combination therapy shifts: The growing use of antibody-drug conjugates (e.g., Enhertu, Kadcyla) in HER2-positive disease may reduce trastuzumab utilization over time, but trastuzumab remains a backbone of many regimens.

Sources

• FDA Biosimilar Product Information. U.S. Food and Drug Administration. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information
• GaBI Online — Biosimilars Approved in the US. https://gabionline.net/biosimilars/general/biosimilars-approved-in-the-us
• Prime Therapeutics — Trastuzumab Medical Necessity Criteria (IC-0057), reviewed December 2025.
• Aetna Clinical Policy Bulletin 0313 — Trastuzumab Products. https://www.aetna.com/cpb/medical/data/300_399/0313.html
• Community Health Choice — Trastuzumab Preferred Product Policy, 2024.
• FEP Blue — Trastuzumab Pharmacy Policy 5.21.006, effective April 2026.
• Mass General Brigham Health Plan — Herceptin Products PA criteria, effective July 2025.
• Fish & Richardson — 2025 Biologics & Biosimilars Landscape. https://www.fr.com/insights/thought-leadership/blogs/biologics-and-biosimilars-landscape-2025-ip-policy-and-market-developments