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Niemann-Pick Disease Type C Agents Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-91237

 

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE                                                                                                                                                                           

Effective Date

Date of Origin 

01-01-2026            

04-01-2025

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Aqneursa™

(levacetylleucine)

Granules for oral suspension

For the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing greater than or equal to 15 kg

1

Miplyffa®

(arimoclomol)

Capsule

For use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older

2

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Niemann-Pick Disease Type C (NPC)

Niemann-Pick Disease Type C (NPC) is a progressive and life-limiting disease caused by mutations in the NPC1 or NPC2 genes, resulting in accumulation of lipids in the lysosomes. NPC is clinically heterogeneous; patients can range from neonates with a rapidly progressive form of the disease to adults with a chronic neurodegenerative condition. Neurological symptoms include loss of motor function, difficulty swallowing, speech impairment, and cognitive impairment. There is no cure for NPC. Current guidelines advocate supportive care measures (physical therapy, lifestyle modifications, pharmacologic treatments for associated comorbidities) and miglustat (off-label) for those with a confirmed diagnosis of NPC.(3,4,5)

Arimoclomol and levacetylleucine (also referred to as N-acetyl-L-leucine or NALL) are two newly available therapies for NPC. Guidelines do not yet include recommendations for their use.(1,2,3)

Efficacy - Aqneursa

Trial 1: A randomized, double-blind, phase 3 clinical trial evaluating the use of levacetylleucine (also referred to as N-acetyl-L-leucine; NALL) in pediatric and adult patients with NPC. The trial consisted of a 2-week baseline period followed by 2 consecutive 12-week treatment periods (Treatment Period 1, Treatment Period 2). At the end of the baseline period, a total of 60 patients were randomized 1:1 to Sequence 1 or Sequence 2 (details below). The primary endpoint in all jurisdictions except the United States was the total score on the Scale for Assessment and Rating of Ataxia (SARA) clinical rating scale. At the request of the Food and Drug Administration (FDA), the primary endpoint in patients from the United States was a modified SARA (mSARA) score. Secondary endpoints evaluated scores on a variety of other rating scales including the modified Disability Rating Scale (mDRS), the Spinocerebellar Ataxia Functional Index (SCAFI), and the Clinical Global Impression of Improvement (CGI-I) scale. Additionally, the Niemann-Pick disease type C Clinical Severity Scale (NPCCSS) score was evaluated as an exploratory measure.(1,7)

Efficacy - Miplyffa

Trial 1: A randomized, double-blind, phase 2/3 clinical trial, evaluated the use of arimoclomol in patients with NPC, in addition to routine clinical care. A total of 50 patients were randomized 2:1 to treatment with arimoclomol or matched placebo for 12 months. The primary endpoint was change from baseline in the 5-domain NPC Clinical Severity Scale (NPCCSS) score. Secondary endpoints included the responder analysis of Clinical Global Impression-Improvement (CGI-I) scores (responder defined as stable or improved) at 12 months; responder analysis of 5-domain NPCCSS scores (responder defined as stable or improved); time to worsening on the NPCCSS assessment (worsening defined as change of 2 points from baseline values); proportion of patients with worsening NPCCSS scores at month 12; and change in the 17-domain NPCCSS (excluding hearing domains) at month 12.(2,6)

The primary endpoint, change from baseline to month 12 in the 5-domain NPCCSS score, demonstrated statistical significance with arimoclomol vs. placebo (mean change, -1.40%; p=0.046). Additionally, patient subgroups, including those receiving concomitant miglustat and those greater than or equal to 4 years old, demonstrated statistically significant improvements in the primary endpoint with arimoclomol treatment vs. placebo. Secondary endpoints did not show statistical differences between treatment arms, although numerical differences favoring arimoclomol were observed.(2,6)

Safety

Aqneursa has no FDA labeled contraindications for use.(1)

Miplyffa has no FDA labeled contraindications for use.(2)

REFERENCES                                                                                                                                                                           

Number

Reference

1

Aqneursa prescribing information. IntraBio Inc. September 2024.

2

Miplyffa prescribing information. Zevra Therapeutics, Inc. September 2024.

3

Geberhiwot T, Moro A, Dardis A, et al. Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018 Apr;13:50. doi: 10.1186/s13023-018-0785-7

4

National Organization for Rare Disorders (NORD). Niemann Pick disease type C. Last updated September 2024. Available at https://rarediseases.org/rare-diseases/niemann-pick-disease-type-c/. 

5

Patterson M. Niemann-Pick disease type C. 2000 Jan 26 [Last updated Dec 2020]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available at https://www.ncbi.nlm.nih.gov/books/NBK1296/

6

Mengel E, Patterson MC, Da Riol RM, et al. Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomized, placebo-controlled, multinational phase 2/3 trial of a novel treatment. J Inherit Metab Dis. 2021 Sep;44:1463-1480. doi: 10.1002/jimd.12428

7

Bremova-Ertl T, Ramaswami U, Brands M, et al. Trial of N-acetyl-L-leucine in Niemann-Pick disease type C. NEJM. 2024 Jan;390:421-431. doi: 10.1056/NEJMoa2310151

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)

Target Generic Agent(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

Miplyffa

arimoclomol citrate cap

124 MG ; 47 MG ; 62 MG ; 93 MG

M ; N ; O ; Y

N

Aqneursa

levacetylleucine for susp packet

1 GM

M ; N ; O ; Y

N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

QL Amount

Dose Form

Day Supply

Duration

Addtl QL Info

Allowed Exceptions

Targeted NDCs When Exclusions Exist

Aqneursa

levacetylleucine for susp packet

1 GM

120

Packets

30

DAYS

Miplyffa

arimoclomol citrate cap

47 MG

90

Capsules

30

DAYS

Miplyffa

arimoclomol citrate cap

62 MG

90

Capsules

30

DAYS

Miplyffa

arimoclomol citrate cap

93 MG

90

Capsules

30

DAYS

Miplyffa

arimoclomol citrate cap

124 MG

90

Capsules

30

DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Aqneursa

levacetylleucine for susp packet

1 GM

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Miplyffa

arimoclomol citrate cap

124 MG ; 47 MG ; 62 MG ; 93 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Aqneursa

levacetylleucine for susp packet

1 GM

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Miplyffa

arimoclomol citrate cap

93 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Miplyffa

arimoclomol citrate cap

62 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Miplyffa

arimoclomol citrate cap

47 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

Miplyffa

arimoclomol citrate cap

124 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Aqneursa

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. ONE of the following:
    1. The requested agent is eligible for continuation of therapy AND ONE of the following:

Agents Eligible for Continuation of Therapy

Aqneursa
      1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
    2. ALL of the following:
      1. The patient has a diagnosis of Niemann-Pick disease Type C AND
      2. Genetic analysis confirms mutation in the NPC1 or NPC2 genes AND
      3. The patient has disease-related neurological symptoms (e.g., loss of motor function, difficulty swallowing, speech impairment, cognitive impairment) AND
      4. The patient weighs greater than or equal to 15 kg AND
  2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  3. The patient will NOT be using the requested agent in combination with Miplyffa AND
  4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 6 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

 

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process (Note: patients not previously approved for the requested agent will require initial evaluation review) AND
  2. The patient has had clinical benefit with the requested agent AND
  3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  4. The patient will NOT be using the requested agent in combination with Miplyffa AND
  5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Miplyffa

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. ONE of the following:
    1. The requested agent is eligible for continuation of therapy AND ONE of the following:

Agents Eligible for Continuation of Therapy

Miplyffa
      1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
    2. ALL of the following:
      1. The patient has a diagnosis of Niemann-Pick disease Type C AND
      2. Genetic analysis confirms mutation in the NPC1 or NPC2 genes AND
      3. The patient has disease-related neurological symptoms (e.g., loss of motor function, difficulty swallowing, speech impairment, cognitive impairment) AND
      4. The requested agent will be used in combination with miglustat AND
      5. If the patient has an FDA labeled indication, then ONE of the following:
        1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
        2. There is support for using the requested agent for the patient’s age for the requested indication AND
  2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  3. The patient will NOT be using the requested agent in combination with Aqneursa AND
  4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

 

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

  1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process (Note: patients not previously approved for the requested agent will require initial evaluation review) AND
  2. The patient has had clinical benefit with the requested agent AND
  3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
  4. The patient will NOT be using the requested agent in combination with Aqneursa AND
  5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Universal QL

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

  1. The requested quantity (dose) does NOT exceed the program quantity limit OR
  2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
    1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
    2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
    3. BOTH of the following:
      1. ​​​​​​​The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication​​​​​​​

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

 

 

 

Commercial _ PS _ Niemann_Pick_Disease_Type_C_Agents_PAQL _ProgSum_ 01-01-2026