CurrentBlue Cross Blue Shield - IowaPolicy 05.04.35

Amondys 45 (casimersen) coverage for Duchenne muscular dystrophy

Wellmark Blue Cross and Blue Shield medical policy on the coverage determination for Amondys 45 (casimersen) for treatment of Duchenne muscular dystrophy (DMD) in patients with mutations amenable to exon 45 skipping; includes clinical rationale, trial summary, safety considerations, and billing code guidance.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyAmondys 45 (casimersen) coverage for Duchenne muscular dystrophy

Policy CodePolicy 05.04.35

Change TypeClarified (policy creation/review)

Effective DateMay 20, 2021

Next Review Date

Key ActionDocument that the indication is for DMD with a confirmed DMD gene mutation amenable to exon 45 skipping; monitor kidney function due to class risk of kidney toxicity with antisense oligonucleotides.

POLICY UPDATE CHANGES

Policy states Amondys 45 is considered not medically necessary for all indications due to insufficient evidence of clinical efficacy.

1Primary drug evaluated

8%Proportion of DMD patients with exon 45 amenable mutations

2025Expected ESSENCE trial completion year

Coverage Summary

Wellmark Blue Cross and Blue Shield medical policy #05.04.35 addresses coverage for Amondys 45 (casimersen) for Duchenne muscular dystrophy (DMD) patients with mutations amenable to exon 45 skipping. The policy scope covers clinical rationale, trial summary, safety considerations, and billing guidance. The policy states that Amondys 45 is not medically necessary for all indications due to insufficient evidence of clinical efficacy. Effective date: 2021-05-20; Last reviewed: 2025-06.

Medical-Necessity Determination

Medical Necessity Determination

Policy statement

Medical Necessity Determination: Amondys 45 (casimersen) is considered not medically necessary for all indications, including the treatment for Duchenne muscular dystrophy (DMD), due to insufficient evidence to demonstrate clinical efficacy.

FDA approved under accelerated approval based on increased dystrophin as a surrogate endpoint; clinical benefit has not been established and confirmatory trials are ongoing.

Not Medically Necessary / Not Covered

Amondys 45 (casimersen) is considered not medically necessary for all indications, including treatment of DMD, because available evidence does not demonstrate clinical efficacy. The drug received FDA accelerated approval (February 2021) based on a surrogate endpoint (increase in dystrophin), but the clinical benefit has not been established and confirmatory trials (ESSENCE) required under accelerated approval are ongoing.

Key evidence informing the non-coverage decision includes interim ESSENCE results used for FDA approval: an interim analysis of 43 evaluable patients at 48 weeks showed mean dystrophin increased to 1.74% of normal from a baseline of 0.93% (n=27), and a between-group difference in change at 48 weeks of 0.59% (p = 0.004). These surrogate marker changes have not been linked to demonstrated functional or clinical benefit in trials, and clinical outcome data from ESSENCE were not available at the time of the policy.

Provider Actions

Denial Risk

Coverage denial for Amondys 45

Claims for Amondys 45 (casimersen) are subject to denial as not medically necessary for all indications, including treatment of Duchenne muscular dystrophy (DMD), per this policy.

J1426

Billing Rule

Use appropriate codes when reporting

Report provider services using appropriate CPT codes, HCPCS (J1426 for casimersen), revenue codes, and ICD diagnostic codes when billing for Amondys 45.

J1426

Documentation Required

Clinical rationale and safety monitoring

Document that the indication is Duchenne muscular dystrophy with a confirmed DMD gene mutation amenable to exon 45 skipping. Monitor kidney function during treatment because kidney toxicity has been observed with some antisense oligonucleotides; document safety monitoring and clinical rationale in the record.

Confirm DMD gene mutation is amenable to exon 45 skipping prior to treatment.
Monitor kidney function regularly due to class risk of kidney toxicity with antisense oligonucleotides.

Background and Definitions

Background: Amondys 45 (casimersen) is an antisense oligonucleotide approved by the FDA under accelerated approval (Feb 2021) for DMD patients with mutations amenable to exon 45 skipping based on an observed increase in dystrophin as a surrogate endpoint. A clinical benefit has not been established. A required post-marketing confirmatory trial, ESSENCE (phase 3, double-blind, placebo-controlled), is ongoing to assess whether Amondys 45 improves motor function; ESSENCE is expected to conclude in 2025 and could lead to withdrawal of approval if clinical benefit is not verified.

Term	Definition
Amondys 45 (casimersen)	An antisense oligonucleotide indicated for treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that is amenable to exon 45 skipping; administered once weekly as an intravenous (IV) infusion. The FDA approved this indication in February 2021 under accelerated approval based on increased dystrophin as a surrogate endpoint; a clinical benefit has not been established.
Exon 45 skipping amenable mutation	A DMD gene mutation that can be targeted by exon 45 skipping to restore the dystrophin reading frame for some patients (accounts for approximately 8% of patients with DMD).

Term

Definition

Amondys 45 (casimersen)

An antisense oligonucleotide indicated for treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that is amenable to exon 45 skipping; administered once weekly as an intravenous (IV) infusion. The FDA approved this indication in February 2021 under accelerated approval based on increased dystrophin as a surrogate endpoint; a clinical benefit has not been established.

Exon 45 skipping amenable mutation

A DMD gene mutation that can be targeted by exon 45 skipping to restore the dystrophin reading frame for some patients (accounts for approximately 8% of patients with DMD).

Revision History

2021-04policy_creation

Policy creation (Policy #05.04.35).

2021-05-20effective_date

Policy effective date.

2025-06reviewLatest

Policy reviewed in June 2025; Amondys 45 (casimersen) is considered not medically necessary for all indications, including treatment for Duchenne muscular dystrophy, due to insufficient evidence to demonstrate clinical efficacy.