FIRDAPSE, Amifampridine Phosphate RUZURGI, Amifampridine Form

Amifampridine (Firdapse®) is potassium channel blocker. FDA Approved Indication(s) Firdapse is indicated for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults and pediatric patients 6 years of age and older. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Firdapse is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Lambert-Eaton Myasthenic Syndrome (must meet all):

1. Diagnosis of LEMS;
   2. Documentation of confirmatory diagnostic test results from one of the following (a or b): a. Repetitive Nerve Stimulation (RNS) testing showing reproducible post-exercise increase in compound muscle action potential (CMAP) amplitude of at least 60 percent compared with pre-exercise baseline value or a similar increment on high- frequency repetitive nerve stimulation without exercise;
      b. If member is unable to complete RNS testing, positive anti-P/Q type voltage- gated calcium channel (VGCC) antibody blood test;
2. Prescribed by or in consultation with a neurologist or neuromuscular specialist;
   4. Age ≥ 6 years;
   5. Documentation of a baseline clinical muscle strength assessment (examples may include but are not limited to the Quantitative Myasthenia Gravis (QMG) score, triple-timed up-and-go test (3TUG), Timed 25-foot Walk test (T25FW)) (see Appendix D);

3. Member does not have a history of seizures;

   7. Dose does not exceed one of the following (a or b): a. Adults and pediatrics weighing ≥ 45 kg: 80 mg (8 tablets) per day; b. Pediatrics weighing < 45 kg: 40 mg (4 tablets) per day. Approval duration: 6 months Page 1 of 6

   CLINICAL POLICY Amifampridine B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Lambert-Eaton Myasthenic Syndrome (must meet all):
6. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
7. Member is responding positively to therapy as evidenced by clinical muscle strength assessments (examples may include but are not limited to the QMG score, 3TUG test, T25FW test) (see Appendix D);
8. Member does not have a history of seizures;
   
   4. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. Adults and pediatrics weighing ≥ 45 kg: 80 mg (8 tablets) per day; b. Pediatrics weighing < 45 kg: 40 mg (4 tablets) per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: Page 2 of 6

   CLINICAL POLICY Amifampridine CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CMAP: compound muscle action potential
    FDA: Food and Drug Administration LEMS: Lambert-Eaton myasthenic syndrome QMG: Quantitative Myasthenia Gravis Appendix B: Therapeutic Alternatives
    Not applicable 3TUG: triple-timed up-and-go test RNS: repetitive nerve stimulation
    T25FW: Timed 25-foot Walk test VGCC: voltage-gated calcium channel Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of seizures; hypersensitivity to amifampridine or another aminopyridine • Boxed warning(s): none reported Appendix D: General Information • QMG is a physician-rated evaluation consisting of 13 assessments of muscle function (e.g., swallowing, speech, forced vital capacity, movement of arms and legs). Each assessment is rated 0 to 3, where 0 indicates “no weakness” and 3 indicates “severe weakness” (lower scores reflect better muscle strength). • The 3TUG is a functional mobility test that requires a patient to stand up from a straight- backed armchair, walk 3 meters, turn around, walk back, and sit down in the chair. Based upon literature reports that a significant change in gait for a similar walk-test is an increase in time of more than 20%, this was incorporated into the secondary endpoint used in the NCT02970162 clinical trial. • The T25FW test, a component of the Multiple Sclerosis Functional Composite, is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The patient was directed to walk a clearly marked 25-foot course as quickly and safely as possible. Following a period of rest, the timed 25-foot walk is repeated to determine an average score.
    Page 3 of 6

    CLINICAL POLICY Amifampridine • During RNS testing, an increase in the CMAP amplitude >100% after exercise or with high-frequency RNS is considered diagnostic of a presynaptic neuromuscular junction disorder, and the increase is frequently even greater. However, some studies have found that a significant number of patients have increments with RNS below 100%; thus, increments of 60 to 99% are strongly supportive of a presynaptic neuromuscular junction disorder.
    • P/Q-type VGCC antibody result is strongly suggestive of LEMS. However, P/Q-type VGCC antibodies are present in a variety of clinical situations where LEMS is not present. While the anti-P/Q-type VGCC antibody test is confirmatory in patients who otherwise have clinical and electrophysiologic features of LEMS, the antibody test alone is not diagnostic, especially in the presence of a malignancy or amyotrophic lateral sclerosis. • On February 1, 2022 the FDA converted the final approval of Ruzurgi to a tentative approval. Due to the 7-year orphan-drug exclusivity for Catalyst’s product Firdapse, the application for Ruzurgi for the treatment of LEMS in patients 6 to less than 17 years of age may not be finally approved for marketing until the period of exclusivity has expired. As a result Ruzurgi is no longer commercially available. V. Dosage and Administration
    Indication LEMS Dosing Regimen Adults and pediatrics weighing ≥ 45 kg:15 mg to 30 mg PO daily, in 3 to 4 divided doses. Dose can be increased by 5 mg daily every 3 to 4 days. The maximum single dose is 20 mg.
    Maximum Dose Adults and pediatrics weighing ≥ 45 kg: 80 mg/day
    Pediatrics weighing < 45 kg: 5 mg to 15 mg PO daily, in 3 to 4 divided doses. Dose can be increased by 2.5 mg daily every 3 to 4 days. The maximum single dose is 10 mg. Pediatrics weighing < 45 kg: 40 mg/day VI. Product Availability
    Tablet: 10 mg VII.