Virginia DUR Quarterly Newsletter

VIRGINIA MEDICAID DUR QUARTERLY NEWSLETTER

Virginia Medicaid DUR Quarterly Newsletter

VOLUME 1, NUMBER 17 DECEMBER 2019

Introduction CONTACT INFORMATION In this issue of the quarterly Drug Utilization Review (DUR) newsletter we look at the first oral GLP-1 Agonist, KDIGO guideline update and ICER reports on DMD therapy. Virginia Department of Medical Assistance Services (DMAS) Pharmacy Department

HOT TOPIC: FDA APPROVES FIRST ORAL GLP-1 http://www.dmas.virginia.gov/ AGONIST

The United States (US) Food and Drug Administration (FDA) approved Magellan Pharmacy Support Center semaglutide tablets (Rybelsus®; Novo Nordisk), the first orally administered Service Authorizations: 1-800-932-6648 Service Authorization Fax: 1-800-932-6651 glucagon-like peptide-1 (GLP-1) receptor agonist. Based on a Priority Review, it Website: garnered an indication as an adjunct to diet and exercise to improve glycemic https://www.virginiamedicaidpharmacyservices.c control in adults with type 2 diabetes mellitus (T2DM). om/default.asp

Safety and efficacy of Rybelsus were evaluated in 8 clinical trials in over 5,800 DUR BOARD MEETINGS adults with T2DM. Similar hemoglobin A1c (HbA1c) reductions were March 12, 2020 September 10, 2020 June 11, 2020 December 10, 2020 demonstrated compared to injectable semaglutide (Ozempic®) and to the injectable GLP-1 agonist liraglutide. Rybelsus also resulted in significant HbA1c improvement over the sodium glucose cotransporter 2 (SGLT2) inhibitor P&T COMMITTEE MEETINGS empagliflozin and the oral dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. March 19, 2020 Moreover, Rybelsus was effective in patients with moderate renal impairment and did not appear to increase major cardiovascular events. While significant EDITORIAL STAFF HbA1c reduction was seen when Rybelsus was added to diet and exercise alone, Rachel Cain, Pharm.D it is not intended for first-line treatment in patients not controlled on diet and DMAS exercise alone, due to an uncertain risk of medullary thyroid carcinoma in humans. Nancy Eldin, Pharm.D Magellan Rx Management

Gradual dose escalation improves gastrointestinal tolerability of Rybelsus. The initial dose is 3 mg orally once daily for 30 days, followed by 7 mg once daily. If

VIRGINIA MEDICAID DUR QUARTERLY NEWSLETTER | Issue 17 2

glycemic targets are not met after 30 days of the 7 mg dose, the daily dose may be increased to 14 mg. Rybelsus must be taken at least 30 minutes prior to the first food, drink, or other oral medication of the day. Patients on once-weekly injectable Ozempic may switch to Rybelsus up to 7 days after the last Ozempic dose.

KDIGO GUIDELINE UPDATE

An update was issued to the 2008 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD). Due to a higher prevalence of HCV infection among CKD patients compared to the general population, HCV screening is now recommended at the time of initial evaluation of CKD, upon initiation of dialysis or transfer from another dialysis center, and at the time of kidney transplant evaluation. Additionally, the effectiveness and safety of oral direct-acting antiviral (DAA) therapy in CKD populations have largely impacted all aspects of HCV management. The updated guidelines recommend that all CKD patients infected with HCV be evaluated for treatment with a DAA. This includes candidates and recipients of kidney transplants and patients with HCV- associated glomerular disease. HCV treatment with interferon is no longer recommended due to poor tolerability, lower sustained virologic response (SVR) rates, and unfavorable outcomes in kidney transplant recipients.

The KDIGO guidelines recommend a DAA regimen be chosen based on patient factors, such as HCV genotype, degree of fibrosis, HCV treatment history, comorbidities, and transplant eligibility. Patients with glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 may be treated with any licensed DAA-based regimen, while a ribavirin-free DAA-based regimen is recommended in advanced CKD (GFR < 30 mL/min/1.73 m2). For kidney transplant recipients, assess potential drug interactions between the DAA regimen and concomitant transplant medications prior to HCV treatment.

The timing of DAA treatment in relation to kidney transplantation should be based on factors such as donor type (living or deceased), wait-list times, and liver fibrosis severity. Other key recommendations address HCV-associated kidney disease management, CKD testing in HCV- infected patients, transplantation of kidneys from HCV-infected donors, prevention of HCV transmission in hemodialysis units, and hepatitis B virus (HBV) and human immunodeficiency virus (HIV) testing.

ICER REPORTS ON DMD THERAPY

The Institute for Clinical and Economic Review (ICER) released their final report on therapies for Duchenne muscular dystrophy (DMD), a genetic condition characterized by progressive muscle weakening that is diagnosed predominantly in boys. DMD affects approximately 400 to 600 live male births each year in the US. ICER assessed the comparative clinical effectiveness and value of the corticosteroid deflazacort (Emflaza®, PTC) and Sarepta’s exon-skipping therapies, eteplirsen (Exondys 51™) and golodirsen (investigational).

DMD affects multiple organ systems. Care is multi- faceted and includes supportive care, such as physical and occupational therapy, to maintain ambulation. Corticosteroids (prednisolone, deflazacort) have been the mainstay of therapy. In September 2016, the first exon-skipping therapy, eteplirsen, was FDA-approved. Eteplirsen works by increasing the production of the deficient protein, dystrophin, to slow disease progression. Approval of another exon-skipping therapy, golodirsen, was denied in August 2019 when the FDA issued a complete response letter to Sarepta expressing concerns of infection and renal toxicity.

ICER determined that there is moderate certainty of comparable or better net health benefits with deflazacort compared to prednisone. Additionally, there is insufficient data to support the net health benefit of adding eteplirsen or golodirsen compared to using corticosteroids and supportive care alone. ICER determined that a discount of at least 73% from deflazacort’s list price would be required to achieve commonly cited cost-effectiveness thresholds. A price could not be suggested for the exon- skipping therapies as there is no compelling evidence to support effectiveness for either drug. Notably, ICER also concluded that overall value should consider contextual benefits, such as deflazacort’s ability to significantly reduce caregiver and family burden.

VIRGINIA MEDICAID DUR QUARTERLY NEWSLETTER | Issue 17 3

ICER recommends that patient groups and clinicians work with manufacturers to design clinical trials that measure patient- centered outcomes when developing effective drug therapies that are available at a fair market price. Additionally, payers should not require attestation of benefits of deflazacort for continued coverage or any renewal criteria for the exon- skipping therapies, since continued clinical decline is expected with both treatments.

December DUR Board Summary

The Board reviewed 10 new medications - Inrebic®, Nourianz™, Nubeqa®, Rozlytrek™, Slynd™, Temixys™, Trikafta™, Turalio™, Xenleta™ and Xpovio™. The Board also reviewed 2 physician administered drugs - Luxturna® and Zolgensma®. Approved service authorization criteria are listed at the end of this newsletter.

The next DUR Board meeting is scheduled for March 12, 2020.

The minutes from the December 2019 meeting can be found at: https://www.virginiamedicaidpharmacyservices.com/provider/drug-utilization-review/

New Clinical Service Authorizations – effective date January 23, 2020

Brand Name Generic Name Indication Inrebic® fedratinib A kinase inhibitor indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).

Nubeqa® darolutamide An androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

Rozlytrek™ entrectinib A kinase inhibitor indicated for the treatment of: • Adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive. • Adult and pediatric patients 12 years of age and older with solid tumors that: o have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, o are metastatic or where surgical resection is likely to result in severe morbidity, and o have progressed following treatment or have no satisfactory alternative therapy.

Temixys™ lamivudine and A combination of two nucleoside reverse transcriptase inhibitors tenofovir disoproxil (lamivudine and tenofovir disoproxil fumarate), is indicated in fumarate combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg.

VIRGINIA MEDICAID DUR QUARTERLY NEWSLETTER | Issue 17 4

Trikafta™ elexacaftor, tezacaftor A combination of ivacaftor, a CFTR potentiator, tezacaftor, and and ivacaftor elexacaftor indicated for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the CFTR gene.

Xenleta™ lefamulin A pleuromutilin antibacterial indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by susceptible microorganisms

Xpovio™ selinexor A nuclear export inhibitor indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Physician Administered Drugs

Luxturna® voretigene An adeno-associated virus vector-based gene therapy indicated for neparvovec-rzyl the treatment of patients with confirmed biallelic RPE65 mutation- associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physician(s).

Zolgensma® onasemnogene An adeno-associated virus vector-based gene therapy indicated for abeparvovec-xioi the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. Limitation of Use: • The safety and effectiveness of repeat administration of Zolgensma have not been evaluated. • The use of Zolgensma in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator dependence) has not been evaluated.

References:

https://www.fda.gov/ https://icer-review.org/ https://kdigo.org/