Xiaflex® (Collagenase Clostridium Histolyticum) – Commercial Medical Benefit Drug Policy

Coverage Summary

Coverage stance: Covered with criteria. Policy number 2026D0099F; effective/last review date: January 1, 2026. Scope: defines medical necessity criteria, continuation criteria, applicable procedure/diagnosis and HCPCS codes, and limitations for Xiaflex use for Dupuytren's contracture and Peyronie's disease under UnitedHealthcare commercial medical benefit drug policy.

Indications covered: Xiaflex is indicated for adult patients with Dupuytren's contracture with a palpable cord and for adult men with Peyronie's disease with a palpable plaque and curvature deformity ≥ 30 degrees at the start of therapy. Overall limitations: dosing per FDA labeling at 0.58 mg per injection; Dupuytren's injections limited to ≤ 3 injections per cord (approximately 4-week intervals) and authorization for no more than ≤ 2 injections per hand; Peyronie's treatment limited to authorization for no more than 2 injections per treatment authorization with cycles and continuation criteria (see policy). Xiaflex for Peyronie's requires Xiaflex REMS certification due to risk of corporal rupture.

Key thresholds and quick facts

Indications Covered2

Max injections per cord (Dupuytren)<= 3 injections per cord

Max injections per hand (Dupuytren)<= 2 injections per hand

Dupuytren contracture threshold (initial)>= 20 degrees

Dupuytren continuation minimal contracture> 5 degrees

Interval between injections (Dupuytren)Approximately 4 weeks

Peyronie's minimum curvature (initial)>= 30 degrees

Dupuytren's Contracture — Initial Therapy Criteria

Dupuytren's Contracture — Continuation of Therapy

Peyronie's Disease — Initial Therapy Criteria

Peyronie's Disease — Continuation of Therapy

Not Medically Necessary / Unproven Uses

Not Medically Necessary / Unproven

Xiaflex is considered unproven and not medically necessary for:

Any uses other than the specified indications (Dupuytren's contracture with a palpable cord and Peyronie's disease with palpable plaque and curvature >= 30 degrees)

Applicable Codes

Applicable CPT / Procedure CodesCPT

20527	Injection, enzyme (e.g., collagenase), palmar fascial cord (i.e., Dupuytren's contracture)
26341	Manipulation, palmar fascial cord (i.e., Dupuytren's cord), post enzyme injection (e.g., collagenase), single cord

Applicable HCPCS (Drug) CodeHCPCS

J0775

Injection, collagenase, clostridium histolyticum, 0.01 mg

Applicable ICD-10 Diagnosis Codes (examples listed)ICD-10

M72.0	Palmar fascial fibromatosis [Dupuytren]
N48.6	Induration penis plastica

HCPCS unit reporting: Xiaflex is reported with HCPCS code J0775 which is defined as 0.01 mg per unit. Therefore, a single FDA‑approved injection of 0.58 mg corresponds to 58 units. Providers should bill units consistent with the actual administered dose (e.g., bill 58 units for a 0.58 mg injection).

Provider Actions & Administrative Requirements

Prior Authorization

Authorization required with criteria documentation

Providers must obtain prior authorization and document that all required criteria are met before Xiaflex is covered. Required documentation includes diagnosis with a palpable cord or plaque, patient age (≥18), provider experience in the relevant condition, degrees of contracture/curvature, prior treatments and timing (no surgery on the selected joint within 90 days), dosing per FDA labeling (0.58 mg per injection), and injection counts/intervals (limits on injections per cord and per hand).

Codes: J0775, 20527, 26341
Emphasize authorization requirement and that documentation must show all listed criteria (diagnosis with palpable cord/plaque; degrees of contracture/curvature; age; provider experience; prior treatments/timing; dosing per FDA labeling; injection counts/intervals).

Documentation Required

Document functional limitation and degree measurements

Clinical Evidence

Evidence summary – Dupuytren's (CORD I/II): Two randomized, double‑blind, placebo‑controlled trials (CORD I and II) evaluated 0.58 mg injections given up to 3 injections per cord on Days 0, 30, and 60, with manipulation ~24 hours after injection; collagenase showed higher rates of contracture reduction to 0°–5° at Day 30 after last injection versus placebo and improved range of motion. Trials included post‑injection finger extension manipulation and splinting/exercises.

Evidence summary – Peyronie's (IMPRESS I/II): Two randomized, double‑blind, placebo‑controlled trials (IMPRESS I and II) studied up to 4 treatment cycles (weeks 0, 6, 12, 18) with each cycle consisting of two injections given 1–3 days apart and a penile modeling procedure 1–3 days after the second injection; collagenase achieved approximately a 33% improvement in curvature and significant reductions in the PDQ Bother score versus placebo. Studies evaluated up to 8 total injections (4 cycles).

Dosing and procedures: Trials used a consistent dose of 0.58 mg per injection, defined manipulation/modeling procedures after injections, and specified cycle schedules (two injections per cycle 1–3 days apart with modeling and repeat cycles at approximately 6‑week intervals). Note REMS/safety: treatment for Peyronie's is available only through the Xiaflex REMS Program because of the risk of corporal rupture (penile fracture).

Background & Definitions

Background and FDA indications: Xiaflex is FDA‑approved for treatment of adult patients with Dupuytren's contracture with a palpable cord and for treatment of adult men with Peyronie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy. Because of the risk of corporal rupture or other serious penile injury when treating Peyronie's disease, Xiaflex is available only through the Xiaflex REMS Program; prescribers and healthcare sites must be certified.

Dosing and injection/cycle definitions: The FDA‑approved dose is 0.58 mg per injection. For Peyronie's disease, two injections given 1–3 days apart constitute one treatment cycle, and cycles may be repeated at approximately 6‑week intervals; for Dupuytren's the typical injection schedule in trials was up to 3 injections per cord given on Days 0, 30, and 60 with manipulation performed about 24 hours after each injection.

Definitions

Injection (dose)FDA-approved dose is 0.58 mg per injection into a palpable cord or plaque

Treatment cycle (Peyronie's)Two injections given 1-3 days apart constitute one cycle; cycles may be repeated at ~6-week intervals

Successful treatment (Dupuytren)Reduction in contracture to 0° to 5° of normal at Day 30 after last injection

Revision History

2026-01-01revisedLatest

Reworded coverage rationale statements to separate 'proven for the treatment' and 'medically necessary when criteria are met' for both Dupuytren's contracture and Peyronie's disease; archived previous policy version 2025D0099E. (See Policy History/Revision Information.)