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Duchenne Muscular Dystrophy Genetic Therapies Approved By: UM Pharmacy Subcommittee

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Duchenne Muscular Dystrophy Genetic Therapies Approved By: UM Pharmacy Subcommittee Original Department: Pharmacy Management 10/12/2020 Approval: Policy #: PM165 Last Approval: 10/12/2020 Title: Duchenne Muscular Dystrophy genetic therapies Approved By: UM Pharmacy Subcommittee Line(s) of Business WAH-IMC (HCA) BHSO Medicare Advantage (CMS) Medicare SNP (CMS) Cascade Select Documentation required to determine medical necessity for Eteplirsen IV infusion (Exondys 51): History and/or physical examination notes and relevant specialty consultation notes that address the problem and need for the service: Diagnosis-Age-Medication list (current and past)- Labs/Diagnostics. BACKGROUND Exondys 51 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.1 Exondys 51 was approved for this indication under accelerated approval based on an increase in dystrophin observed in the skeletal muscle of some patients who received the drug. However, a clinical benefit of Exondys has not been established. The prescribing information notes that continued FDA-approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Golodirsen (Vyondys 53) and Viltolarsen (Viltepso) are indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping.1,12 Vyondys 53 and Viltepso were approved for this indication under accelerated approval based on an increase in dystrophin observed in the skeletal muscle of patients who received the drug. The prescribing information notes that continued FDA-approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials. Disease Overview DMD is an X-linked recessive disease affecting 1 in 3,600 to 6,000 newborn male infants.2 The disease is attributed to large frame-shift deletions in the DMD gene (chromosome Xp21) which lead to loss of a structural protein of muscle cells (dystrophin).3 Over 4,700 mutations on the DMD gene have been identified which lead to a deficiency in production of dystrophin.2 Therefore, the type of mutation and its effect on the production of dystrophin accounts for the variable phenotypic expression.4 Females carriers are usually asymptomatic but some may show mild symptoms.2 There are wide variances in how quickly DMD progresses, but without intervention death is at approximately 19 years of age.2-4 With respiratory, cardiac, orthopedic and rehabilitative interventions and use of corticosteroids, children born today can have a life expectancy of up to 40 years. Exondys 51 is an antisense oligonucleotide designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to PM165_CCC_Duchenne Muscular Dystrophy genetic therapies 1 of 7 DATA CONTAINED IN THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY INFORMATION AND ITS DUPLICATION USE OR DISCLOSURE IS PROHIBITED WITHOUT PRIOR APPROVAL OF COMMUNITY HEALTH PLAN OF WASHINGTON. exon 51 skipping.1 These patients represent approximately 13% of all patients with DMD.5 This genetic manipulation intends to restore the reading frame of the resulting mRNA. The result would be production of a shortened, but partially functional dystrophin protein as seen in less severe forms of muscular dystrophy (e.g., Becker muscular dystrophy). Vyondys 53 is an antisense oligonucleotide designed to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping.12 These patients represent up to 10% of all patients with DMD.5 This genetic manipulation intends to restore the reading frame of the resulting mRNA. The result would be production of a shortened, but partially functional dystrophin protein as seen in less severe forms of muscular dystrophy (e.g., Becker muscular dystrophy). Of note, the reading frame of certain deletions (e.g., exon 52 deletions) can be restored by skipping either exon 51 or exon 53.6 Approximately 8% of mutations are amenable to skipping exon 53 with Vyondys 53 but are not amenable to skipping of exon 51. Guidelines There are guidelines for the diagnosis and management of DMD available from the DMD Care Considerations Working Group (2018).4 Genetic testing for a DMD mutation in a blood sample is always required. By fully characterizing the mutation, the predicted effect on the reading frame can be identified, which is the major determinant of phenotype and will determine eligibility for mutation-specific clinical trials. In patients with no mutation identified but with signs/symptoms of DMD, a muscle biopsy is clinically indicated. Glucocorticoids slow decline in muscle strength and function in DMD. Use of corticosteroids reduces the risk of scoliosis and stabilizes pulmonary function. Continued treatment after the patient loses ambulation provides a reduction in the risk of progressive scoliosis and stabilization of pulmonary function tests. Therefore, glucocorticoids should be considered for all patients with DMD. Exondys 51 is mentioned as an emerging product, approved by an accelerated pathway for those with a mutation in the dystrophin gene amenable to exon 51 skipping. DEFINITIONS none INDICATIONS/CRITERIA CHPW AH-IMC Excluded benefit. Authorization and billing required directly through WA members Apple Health Fee For Service only. Call 800-562-3022. CHNW Cascade Select Continue to criteria for approval below. members Medicare Members Step-utilization of Part D drugs not required. Continue to criteria for approval below. Coverage of Eteplirsen IV infusion (Exondys 51) is recommended in those who meet the following criteria: FDA-Approved Indications PM165_CCC_Duchenne Muscular Dystrophy genetic therapies 2 of 7 DATA CONTAINED IN THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY INFORMATION AND ITS DUPLICATION USE OR DISCLOSURE IS PROHIBITED WITHOUT PRIOR APPROVAL OF COMMUNITY HEALTH PLAN OF WASHINGTON. Treatment of Duchenne muscular dystrophy (DMD) Initial Approval Approve for 3 months for patients who meet ALL the following criteria: 1. Diagnosis of Duchenne muscular dystrophy by, or in consultation with, a neurologist with expertise in the diagnosis of DMD; 2. Results of genetic testing confirm Duchenne muscular dystrophy amenable to exon 51 skipping; 3. Patient is 4 years of age or older 4. Patient has stable pulmonary (absence of invasive ventilation or tracheostomy) and cardiac function 5. Patient is receiving glucocorticoid therapy or glucocorticoid treatment was discontinued at the recommendation of the treating physician 6. Results of 6-Minute Walk Time (6MWT) ≥ 300 meters while walking independently (e.g., without side-by-side assist, cane, walker, wheelchair, etc.) prior to beginning Eteplirsen (Exondys 51) therapy; OR Brooke Upper Extremity Functional Rating Scale for non-ambulatory patients: baseline of 5 or lower 7. Eteplirsen (Exondys 51) is prescribed by, or in consultation with, a neurologist with expertise in the treatment of DMD; 8. Dosing is 30 mg/kg infused once weekly for DMD is in accordance with the United States Food and Drug Administration approved labeling; 9. Eteplirsen (Exondys 51) is not used concomitantly with other exon skipping therapies for DMD (e.g., Vyondys 53, Viltepso, or other clinical trial agents); For reauthorization: Approve for 6 months for patients who meet ALL the following criteria: 1. Eteplirsen (Exondys 51) is prescribed by, or in consultation with, a neurologist with expertise in the treatment of DMD; 2. Maintenance or improvement of 6-Minute Walk Time (6MWT) ≥ 300 meters while walking independently (e.g., without side-by-side assist, cane, walker, wheelchair, etc.). This must be measured no earlier than 4 weeks prior to a continuation request; OR Maintenance or improvement in Brooke Upper Extremity Functional Rating Scale for non-ambulatory patients; 3. Patient has stable pulmonary (absence of invasive ventilation or tracheostomy) and cardiac function; 4. Patient is receiving glucocorticoid therapy or glucocorticoid treatment was discontinued at the recommendation of the treating physician; 5. Dosing is 30 mg/kg infused once weekly for DMD is in accordance with the United States Food and Drug Administration approved labeling; 6. Eteplirsen (Exondys 51) is not used concomitantly with other exon skipping therapies for DMD (e.g., Vyondys 53, Viltepso, or other clinical trial agents); PM165_CCC_Duchenne Muscular Dystrophy genetic therapies 3 of 7 DATA CONTAINED IN THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY INFORMATION AND ITS DUPLICATION USE OR DISCLOSURE IS PROHIBITED WITHOUT PRIOR APPROVAL OF COMMUNITY HEALTH PLAN OF WASHINGTON. Coverage of Golodirsen (Vyondys 53) or Viltolarsen (Viltepso) is recommended in those who meet the following criteria: FDA-Approved Indications Treatment of Duchenne muscular dystrophy (DMD) Initial Approval Approve for 3 months for patients who meet ALL the following criteria: 1. Diagnosis of Duchenne muscular dystrophy by, or in consultation with, a neurologist with expertise in the diagnosis of DMD; 2. Results of genetic testing confirm Duchenne muscular dystrophy amenable to exon 53 skipping; 3. Patient is 4 years of age or older 4. Patient has stable pulmonary (absence of invasive ventilation or tracheostomy) and cardiac function 5. Patient is receiving glucocorticoid therapy or glucocorticoid treatment was discontinued
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