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 |
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
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: A. The requested agent is eligible for continuation of therapy AND ONE of the following:
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 B. 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 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 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 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: A. The requested agent is eligible for continuation of therapy AND ONE of the following:
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 B. 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 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: A. The patient’s age is within FDA labeling for the requested indication for the requested agent OR B. 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 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 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. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
|
Module |
Ops Set Up |
Validation Options |
Other Explanation |
|
Aqneursa |
Validation: Apply Baseline and go to Validation Options |
Continuation of Therapy |
|
|
Miplyffa |
Validation: Apply Baseline and go to Validation Options |
Age Verification;Continuation of Therapy |
|
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. 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 boxed warnings nor contraindications.(1) Miplyffa has no boxed warnings nor contraindications.(2) |
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;13:50. |
4 |
National Organization for Rare Disorders. Niemann Pick Disease Type C. 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 [Updated 2020 Dec 10]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: 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;44:1463-1480. |
7 |
Bremova-Ertl T, Ramaswami U, Brands M, et al. Trial of N-Acetyl-L-Leucine in Niemann-Pick Disease Type C. NEJM. 2024;390:421-431. |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Final Module |
Target Agent GPI |
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Targeted NDCs When Exclusions Exist |
Final Age Limit |
Preferred Status |
Effective Date |
|
|||||||||
|
620000230030 |
Aqneursa |
levacetylleucine for susp packet |
1 GM |
M ; N ; O ; Y |
|
|
|
11-14-2024 |
|
620000032001 |
Miplyffa |
arimoclomol citrate cap |
124 MG ; 47 MG ; 62 MG ; 93 MG |
M ; N ; O ; Y |
|
|
|
11-14-2024
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Wildcard |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Targeted NDCs When Exclusions Exist |
Age Limit |
Effective Date |
Term Date |
|
|||||||||||
62000023003020 |
Aqneursa |
levacetylleucine for susp packet |
1 GM |
120 |
Packets |
30 |
DAYS |
|
|
11-14-2024 |
|
62000003200120 |
Miplyffa |
arimoclomol citrate cap |
47 MG |
90 |
Capsules |
30 |
DAYS |
|
|
11-14-2024 |
|
62000003200130 |
Miplyffa |
arimoclomol citrate cap |
62 MG |
90 |
Capsules |
30 |
DAYS |
|
|
11-14-2024 |
|
62000003200140 |
Miplyffa |
arimoclomol citrate cap |
93 MG |
90 |
Capsules |
30 |
DAYS |
|
|
11-14-2024 |
|
62000003200150 |
Miplyffa |
arimoclomol citrate cap |
124 MG |
90 |
Capsules |
30 |
DAYS |
|
|
11-14-2024 |
|
