CurrentPremera BluecrossPolicy 5.01.578

PHARMACY MEDICAL POLICY 5.01.578 Amyotrophic Lateral Sclerosis (ALS) Medications

Defines medical necessity criteria, benefit application (medical vs pharmacy), length of approval, documentation requirements, coding, and coverage-specific criteria for several ALS medications including edaravone (Radicava and generic IV and ORS), tofersen (Qalsody), and riluzole formulations (Teglutik/Tiglutik). Applies to Premera commercial (not Medicare Advantage).

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY MEDICAL POLICY 5.01.578 Amyotrophic Lateral Sclerosis (ALS) Medications

Policy CodePolicy 5.01.578

Change TypeMultiple updates (additions, removals, criteria revisions)

Effective DateJul 1, 2025

Next Review Date

Key ActionSubmit office visit notes with diagnosis, relevant history, physical evaluation, medication, respiratory function tests, and other relevant information demonstrating that medical necessity criteria are met.

POLICY UPDATE CHANGES

Added generic edaravone IV to policy with the same policy criteria as Radicava IV.

Updated Qalsody (tofersen) criteria removing disease duration requirement of 2 years or less and changed respiratory threshold to SVC >=65% or FVC >=50%.

Added coverage for Radicava ORS (edaravone) (2022) with same criteria as IV formulation.

Removed Relyvrio (sodium phenylbutyrate and taurursodiol) after market withdrawal.

Removed Exservan (riluzole) as product was withdrawn from the market.

3Medications with coverage criteria (major)

2Managed via pharmacy benefit

3Managed via medical benefit

>=1Investigational uses

Coverage Summary

Policy Number 5.01.578 — Status: CURRENT. Effective date: 2025-07-01; Last review: 2025-03-01. Scope: defines medical necessity criteria, benefit application (medical vs pharmacy), length of approval, documentation and coding for ALS medications.

Coverage stance: covered_with_criteria. Drugs covered with criteria: Edaravone IV (Radicava and generic edaravone IV) and Radicava ORS (edaravone) — managed via the medical benefit for IV formulations and pharmacy benefit for ORS as specified; Qalsody (tofersen) — managed via the medical benefit; and Teglutik/Tiglutik (riluzole oral suspensions) — managed via the pharmacy benefit. Coverage is subject to the policy’s diagnostic, functional and respiratory thresholds and prescriber requirements.

Quick thresholds & facts

Edaravone respiratory thresholdFVC >= 70% of predicted

Edaravone disease durationDisease duration <= 2 years

Qalsody ageAge >= 18 years

Qalsody functionality (ALSFRS-R)ALSFRS-R score >= 37 points

Qalsody respiratory thresholdSVC >= 65% of predicted OR FVC >= 50% of predicted

Riluzole suspensions ageAge >= 18 years

Policy dates & numberEffective date 2025-07-01; Last review 2025-03-01; Policy number 5.01.578

Initial Therapy Criteria

Edaravone (generic edaravone IV / Radicava IV / Radicava ORS) - Medical Necessity

May be considered medically necessary when ALL of the following criteria are met:

ALL of the following

Diagnostic findings (ALL required)
- Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination
- AND/OR evidence of upper motor neuron (UMN) degeneration by clinical examination
- Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination
- Absence of electrophysiological or pathological evidence of other disease processes that might explain the signs of LMN and/or UMN degeneration

Continuation Therapy Criteria

Typical approval durations: most listed drugs (Qalsody, generic edaravone, Radicava IV, Radicava ORS) may be approved for up to 6 months; Teglutik/Tiglutik (riluzole suspensions) and non-formulary exception reviews may be approved up to 12 months as specified.

Re-authorization/continuation requires documentation of ongoing clinical benefit in the medical record (office visit notes, diagnosis, relevant history, physical evaluation, current medications, respiratory function tests and other information) demonstrating continued positive clinical response or ability to perform most activities of daily living.

Non-formulary exception reviews for any drug in the policy may be authorized for up to 12 months; other approvals for most listed drugs are generally up to 6 months per the policy’s billing rules and provider documentation requirements.

Unproven / Other Uses

Other uses

All other uses of the medications listed in this policy are:

Considered investigational

Several products were removed from coverage after market withdrawal: Relyvrio was removed in 2024 after withdrawal from the market, and Exservan (riluzole) was removed following manufacturer discontinuation effective September 30, 2024. These withdrawn products are no longer covered under the policy.

Applicable Codes

HCPCS codes (medical benefit injectable/IT agents)HCPCSCovered

J1301	Injection, edaravone (Radicava), mg
J1304	Injection; tofersen (Qalsody), mg

Other HCPCS historically referencedHCPCS

C9157

Previously added code now termed (document history)

Provider Actions

Prior Authorization

Prior authorization required per medical/pharmacy benefit assignment

Qalsody (tofersen), generic edaravone, and Radicava (edaravone) products are managed through the medical benefit and require prior authorization; Radicava ORS (edaravone), Teglutik (riluzole), and Tiglutik (riluzole) are managed through the pharmacy benefit and require prior authorization.

J1301
J1304

Documentation Required

Required medical record documentation

Submit office visit notes that document the diagnosis and relevant history, the physical evaluation, current medications, respiratory function tests, and other relevant clinical information to demonstrate that the medical necessity criteria are met.

Clinical Evidence

Significant slowing of ALSFRS-R decline vs placeboRadicava trial (6-month)

No ALSFRS-R benefit at 28 weeks; reductions in plasma NfL and CSF SOD1Tofersen trial (28-week)

Evidence summary: The Radicava randomized 6‑month trial demonstrated a significant slowing of ALSFRS‑R decline versus placebo in a population meeting El Escorial criteria and other entry thresholds. The tofersen 28‑week randomized trial showed no statistically significant ALSFRS‑R benefit at 28 weeks but demonstrated significant reductions in plasma NfL and CSF SOD1 protein. The policy’s criteria and use align with the FDA prescribing information for these products.

Background

Background: This policy outlines coverage for ALS medications with diagnostic requirements based on the El Escorial criteria (evidence of LMN and/or UMN degeneration and progressive spread) and includes functional and respiratory thresholds (e.g., ALSFRS‑R and FVC/SVC thresholds). It references the pivotal randomized Radicava 6‑month trial and the tofersen 28‑week trial and states that policy criteria align with FDA prescribing information.

Definitions (short): ALSFRS‑R — ALS Functional Rating Scale‑Revised, 12‑item scale (higher scores = greater function); LMN — lower motor neuron; UMN — upper motor neuron; FVC — forced vital capacity (% predicted); SVC — slow vital capacity (% predicted).

Revision History

2022added

Added coverage for Radicava ORS (edaravone oral suspension) based on bioequivalence to IV formulation; same criteria as Radicava IV.

04/01/23added

Added coverage for Relyvrio (sodium phenylbutyrate and taurursodiol) for treatment of ALS.

07/01/24removed

Removed Relyvrio (sodium phenylbutyrate and taurursodiol) after market withdrawal.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY MEDICAL POLICY 5.01.578 Amyotrophic Lateral Sclerosis (ALS) Medications

Policy CodePolicy 5.01.578

Change TypeMultiple updates (additions, removals, criteria revisions)

Effective DateJul 1, 2025

Next Review Date

On This Page

Absence of neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiologic signs

Normal respiratory function is retained defined as forced vital capacity (FVC) is at least 70% of predicted>= 70% of predicted

Has disease duration of 2 years or less<= 2 years

Medication is prescribed by or in consultation with a neurologist or ALS specialist

Prescriber requirement included in policy history and criteria

Qalsody (tofersen) intrathecal - Medical Necessity

May be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 18 years or older>= 18 years
Diagnostic findings (ALL required)
- Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination
- AND/OR evidence of upper motor neuron (UMN) degeneration by clinical examination
- Progressive spread of symptoms or signs within a region or to other regions, as determined by history or examination
- Absence of electrophysiological or pathological evidence of other disease processes that might explain the signs of LMN and/or UMN degeneration
- Absence of neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysical signs
Has a confirmed mutation in the superoxide dismutase 1 (SOD1) gene
Functionality is retained for most activities of daily living defined as a score of 37 or more points on ALS Functional Rating Scale-Revised (ALSFRS-R)>= 37 points
Slow vital capacity (SVC) of 65% or greater OR forced vital capacity (FVC) of 50% or greaterSVC >= 65% OR FVC >= 50%
Updated to allow SVC >=65% or FVC >=50%
Medication is prescribed by or in consultation with a neurologist or ALS specialist

Teglutik (riluzole) / Tiglutik (riluzole) oral suspension - Medical Necessity

May be considered medically necessary when ALL of the following criteria are met:

ALL of the following

The individual is aged 18 years or older>= 18 years
Prior therapy / clinical necessity (ONE of)
- Has tried generic riluzole tablets first and had an inadequate response or intolerance to generic riluzole tablets
- Documentation is provided that oral suspension is clinically necessary (e.g., trouble swallowing)
Medication is prescribed by or in consultation with a neurologist or ALS specialist

Office visit notes including diagnosis and relevant history

Physical examination findings

Current medication list

Respiratory function test results (e.g., SVC, FVC)

Any other relevant clinical documentation supporting medical necessity

Documentation Required

Prescriber specialty requirement

Medications in this policy must be prescribed by or in consultation with a neurologist or an ALS specialist as specified in the individual drug coverage criteria.

Billing Rule

Non-formulary exception review length

Non-formulary exception reviews for all drugs listed in the policy may be approved for up to 12 months. Most other initial approvals for listed drugs (Qalsody, generic edaravone, Radicava and Radicava ORS) are generally approved up to 6 months; approvals for Teglutik and Tiglutik may be approved up to 12 months. Specific authorization lengths vary by drug and review type.

Non-formulary exception reviews: up to 12 months
Qalsody, generic edaravone, Radicava (IV) and Radicava ORS: most other reviews up to 6 months
Teglutik and Tiglutik reviews: may be approved up to 12 months

09/30/24removed

Exservan (riluzole) withdrawn by manufacturer and removed from the policy.

03/01/25revised

Updated Qalsody (tofersen) criteria by removing the disease duration requirement of 2 years or less.

07/01/25added

Added generic edaravone IV to the policy with the same medical necessity criteria as Radicava (edaravone) IV.

08/01/25revisedLatest

Interim review clarified Qalsody respiratory thresholds changing SVC requirement to 'SVC >=65% or FVC >=50%'; also removed the disease duration cap (previously removed March 2025) and clarified non-formulary exception review authorizations may be approved up to 12 months.