ph-91140
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Fintepla (fenfluramine) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-91140

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

Fintepla Prior Authorization with Quantity Limit Criteria

TARGET AGENT(S)

Fintepla® (fenfluramine)

Brand (generic)

GPI

Multisource Code

Quantity Limit

(per day or as listed)

Fintepla (fenfluramine)

2.2 mg/mL oral solution

72600028102020

M, N, O, or Y

1 bottle (360 mL) / 30 days

PRIOR AUTHORIZATION CRITERIA FOR APPROVAL

Initial Evaluation

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

  1. ONE of the following:
    1. BOTH of the following:
      1. The patient has a diagnosis of seizure associated with Dravet syndrome

AND

      1. The requested agent will NOT be used as monotherapy for seizure management

OR

    1. The patient has another FDA approved indication for the requested agent and route of administration

AND

  1. ONE of the following:
    1. The patient’s age is within FDA labeling for the requested indication for the requested agent

OR

    1. The prescriber has provided information in support of using the requested agent for the patient’s age

AND

  1. An echocardiogram assessment will be obtained before and during treatment with the requested agent, to evaluate for valvular heart disease and pulmonary arterial hypertension

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

Length of Approval:  12 months

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

AND

  1. The patient has had clinical benefit with the requested agent

AND

  1. If using for seizure management, the requested agent will NOT be used as monotherapy
    AND
  2. An echocardiogram assessment will be obtained during treatment with the requested agent, to evaluate for valvular heart disease and pulmonary arterial hypertension

AND

  1. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis

AND

  1. The patient does NOT have any FDA labeled contraindications to the requested agent

AND

  1. ONE of the following:
    1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

    1. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

AND

      1. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

Length of Approval:  12 months

FDA APPROVED INDICATIONS AND DOSAGE1

Agent(s)

Indication(s)

Dosage

Fintepla®

(fenfluramine)

Oral solution

Treatment of seizures associated with Dravet syndrome in patients 2 years of age and older

Initial starting dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability (titration table in package labeling). Titration is based on whether the patient is taking concomitant stiripentol and clobazam.

Maximum maintenance dosage in patients not on concomitant stiripentol is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).

Maximum maintenance dosage in patients taking concomitant stiripentol and clobazam is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg).

CLINICAL RATIONALE

Dravet syndrome (DS) is a severe form of epilepsy characterized by frequent, prolonged seizures and neurodevelopmental problems beginning in infancy. Mutations in the alpha-1 subunit of the voltage-gated sodium channel (SCN1A) gene are identified in 70-85% of patients with DS. Status epilepticus, or a seizure lasting longer than 5 minutes and sometimes 30 minutes or more, is common. Additional seizure types, including myoclonic, atypical absence, and complex partial seizures, appear before age 5 years. Mortality in DS is elevated above that found in the general epilepsy population, with an estimated mortality of 15-20% by adulthood. First-line treatment is typically valproate, with clobazam added if needed. Additional agents include stiripentol, topiramate, and levetiracetam. For patients with symptoms refractory to drug therapy, ketogenic diet and vagal nerve stimulation may be beneficial.2-4

The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with DS are unknown. Fenfluramine and its metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors.1

Efficacy

The effectiveness of fenfluramine for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older was established in two randomized, double-blind, placebo-controlled trials in patients 2 to 18 years of age. Study 1 (N=117) compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of fenfluramine with placebo in patients who were NOT receiving stiripentol. Study 2 (N=85) compared a 0.4 mg/kg/day dose of fenfluramine with placebo in patients who were receiving stiripentol and either clobazam, valproate, or both. In both studies, patients had a clinical diagnosis of Dravet syndrome and were inadequately controlled on at least one antiepileptic drug (AED) or other antiseizure treatment including vagal nerve stimulation or a ketogenic diet. In Study 1, 98% of patients were taking 1-4 concomitant AEDs; in Study 2, 100% were taking 2-4 concomitant AEDs.1,5,6

The primary efficacy endpoint in both studies was the change from baseline in the frequency of convulsive seizures per 28 days during the treatment period. For Study 1, the percent reduction in monthly convulsive seizure frequency was 70% for the 0.7 mg/kg/day dose (P < 0.001) and 31.7% for the 0.2 mg/kg/day dose (P=0.043); for Study 2 it was 59.5% reduction (P < 0.001). A reduction in convulsive seizures was observed within 3-4 weeks of starting fenfluramine, and the effect remained generally consistent over the 14- or 15-week treatment period.1,5,6

A secondary endpoint was longest seizure-free interval, for which the median longest seizure-free intervals in the 0.7 mg/kg/day, 0.4 mg/kg/day, and 0.2 mg/kg/day groups were 25 days, 22 days, and 15 days, respectively.5,6

Safety1

Fintepla carries a boxed warning for valvular heart disease and pulmonary arterial hypertension. There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine, and valvular heart disease and pulmonary arterial hypertension. Echocardiogram assessments are required before, during, and after treatment with Fintepla; benefits versus risks of initiating or continuing must be considered based on echocardiogram findings. Because of these risks, Fintepla is available only through the Fintepla REMS program.

Fintepla has the following contraindications:

  • Concomitant use of, or within 14 days of the administration of, monoamine oxidase inhibitors because of an increased risk of serotonin syndrome.
  • Hypersensitivity to fenfluramine or any of the excipients in Fintepla.

REFERENCES

  1. Fintepla prescribing information. Zogenix, Inc. June 2020.
  2. Wirrell EC, Laux L, Donner E, et al. Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations from a North American Consensus Panel. Pediatr Neurol. 2017;68:18-34.
  3. Sullivan J, Knupp K, Wirrell E. Dravet Syndrome. National Organization for Rare Disorders (NORD). Available at https://rarediseases.org/rare-diseases/dravet-syndrome-spectrum/. Accessed July 2020.
  4. Andrade DM, Nascimento FA, et al. Dravet Syndrome: Management and Prognosis. UpToDate. Literature review current through June 2020. Last updated June 2020. Accessed July 2020.
  5. Lagae L, Sullivan J, Knupp K, et al. Fenfluramine Hydrochloride for the Treatment of Seizures in Dravet Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Lancet. 2019;394(10216):2243-2254.
  6. Nabbout R, Mistry A, Zuberi S, et al. Fenfluramine for Treatment-Resistant Seizures in Patients with Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. JAMA Neurol. 2020;77(3):300-308.

 

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 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.

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