CurrentCignaPolicy N/A

Metabolic Disorders - Carbaglu Prior Authorization Policy

Defines prior authorization requirements, coverage criteria, approval durations, and non-covered uses for Carbaglu (carglumic acid) for Cigna-administered health benefit plans, focusing on NAGS deficiency and acute hyperammonemia in propionic/methylmalonic acidemias.

Policy Summary

PayerCigna

PolicyMetabolic Disorders - Carbaglu Prior Authorization Policy

Policy CodePolicy N/A

Change TypeAnnual revision — no criteria changes

Effective Date

Next Review Date

Key ActionPrior authorization is recommended; obtain required diagnostic documentation and ensure prescribing by or in consultation with a metabolic disease specialist.

POLICY UPDATE CHANGES

Annual Revision noted: 'No criteria changes' for review dates 01/18/2023, 01/17/2024, and 02/05/2025.

2Covered Indications

7Acute approval (days)

1Max approval (years)

Coverage Summary

Carbaglu (carglumic acid) is indicated as adjunct therapy for N-acetylglutamate synthase (NAGS) deficiency with acute or chronic hyperammonemia and for acute hyperammonemia in propionic acidemia or methylmalonic acidemia. For propionic/methylmalonic acute treatment, therapy should be continued until plasma ammonia is 50 micromol/L and for a maximum of 7 days.

This policy and its prior authorization requirements apply to Cigna-administered health benefit plans, defining coverage criteria, required documentation (including genetic confirmation or laboratory ammonia values), specialist involvement, approval durations (up to 1 year for genetically confirmed NAGS, 3 months for provisional NAGS diagnosis by ammonia laboratory criteria, and 7 days for acute propionic/methylmalonic hyperammonemia), and non-covered long-term uses.

Initial Therapy Criteria (FDA-Approved Indications)

FDA-Approved Indications

Carbaglu is covered as medically necessary when ALL required criteria for the indicated condition are met.

N-Acetylglutamate Synthase (NAGS) Deficiency with Hyperammonemia

Diagnosis is supported by ONE of the following
- Genetic confirmation: Genetic testing confirmed a mutation leading to N-acetylglutamate synthase deficiency
  If met, approve for 1 year
- Laboratory diagnosis: Patient has hyperammonemia diagnosed with an ammonia level above the upper limit of the normal reference range for the reporting laboratoryAbove lab-specific upper limit (age-dependent)
  If met, approve for 3 months; ammonia reference ranges are age-dependent
Concurrent management: Medication is prescribed in conjunction with a protein-restricted diet
Specialist involvement: Medication is prescribed by or in consultation with a metabolic disease specialist (or specialist who focuses on the treatment of metabolic diseases)

Propionic Acidemia or Methylmalonic Acidemia with Hyperammonemia — Acute Treatment

Ammonia threshold: Patient's plasma ammonia level is ≥ 50 micromol/L>= 50 micromol/L
Approve for 7 days when criteria met
Concurrent therapies: Medication is prescribed in conjunction with other ammonia-lowering therapies (examples: intravenous glucose, insulin, L-carnitine, protein restriction, dialysis)
Specialist involvement: Medication is prescribed by or in consultation with a metabolic disease specialist (or specialist who focuses on the treatment of metabolic diseases)

Conditions Not Covered (Experimental/Investigational/Unproven)

Carbaglu is considered experimental, investigational, or unproven for any other uses not specified above.

Not covered: Propionic/Methylmalonic maintenance: Propionic acidemia or methylmalonic acidemia with hyperammonemia — Maintenance (chronic use beyond 7 days) is not indicated; no clinical evidence supports long-term use in these disorders>7 days

Chronic use beyond 7 days is considered experimental/investigational and is not covered.

Carbaglu is considered experimental, investigational, or unproven for any other uses not specified above, including chronic (maintenance) use of Carbaglu beyond 7 days for propionic acidemia or methylmalonic acidemia.

Provider Actions and Authorization Requirements

Prior Authorization

Prior authorization required

Prior authorization is recommended for prescription benefit coverage of Carbaglu; approvals provided for durations specified and require prescribing by or in consultation with a metabolic disease specialist.

Documentation Required

Diagnostic documentation required

For NAGS deficiency provide genetic testing confirming mutation OR documentation of hyperammonemia (lab ammonia above lab-specific upper limit). For propionic/methylmalonic acute treatment provide plasma ammonia value (>=50 micromol/L) and documentation of concurrent ammonia-lowering therapies.

Billing Rule

Approval durations

If genetic confirmation of NAGS deficiency: approve for 1 year; if NAGS diagnosed by hyperammonemia lab only: approve for 3 months; for acute propionic/methylmalonic hyperammonemia: approve for 7 days (continue until ammonia <50 micromol/L, max 7 days).

Denial Risk

Not covered for long-term use in propionic/methylmalonic acidemia

Chronic use of Carbaglu beyond 7 days for propionic or methylmalonic acidemia is considered experimental/investigational and is not covered.

Documentation Required

Specialist involvement required

Carbaglu must be prescribed by or in consultation with a metabolic disease specialist or similar specialist focusing on metabolic diseases.

Clinical Evidence & References

Prescribing information: Carbaglu tablets [prescribing information], Recordati Rare Diseases; January 2024.

Guideline: Forny P et al., 2021 — Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia, which support inclusion of Carbaglu in the initial management of symptomatic hyperammonemia.

Background and Definitions

Carbaglu is a synthetic analog of N-acetylglutamate that activates carbamoyl phosphate synthetase 1 (CPS1), the first reaction in the urea cycle, facilitating ammonia conversion to urea.

It is indicated for NAGS deficiency (patients often present in the neonatal period with poor feeding, vomiting, lethargy, seizures, and hyperammonemia) and for acute hyperammonemia in propionic and methylmalonic acidemias as adjunctive therapy.

Although genetic testing is required to confirm NAGS deficiency, treatment with Carbaglu may be initiated empirically as soon as the disorder is suspected or for unexplained hyperammonemia while awaiting confirmatory testing.

Term	Definition
NAGS	N-acetylglutamate synthase
Hyperammonemia	Elevated blood ammonia; specific laboratory upper limits are dependent on patient age and the reporting laboratory