Drug and Biologic Coverage Criteria

Effective Date ...... 8/1/2020 Next Review Date… ...... 8/1/2021 Coverage Policy Number ...... P0011

Isavuconazonium

Table of Contents Related Coverage Resources

Medical Necessity Criteria ...... 1 FDA Approved Indications ...... 2 Recommended Dosing ...... 2 Background ...... 2 References ...... 3

INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

Medical Necessity Criteria

This coverage policy addresses the use of oral isavuconazonium. The use of intravenous isavuconazonium is not addressed in this coverage policy.

Isavuconazonium (Cresemba®) is considered medically necessary when ANY of the following are met: • Continuation therapy of documented Cresemba initiated by IV infusion • Treatment of invasive aspergillosis • Treatment of invasive mucormycosis • Treatment of invasive candidiasis/candidemia when there is documented failure or contraindication per FDA label, intolerance to, or not a candidate (for example, critically ill, fluconazole-resistant organism, or history of prior exposure to azoles) for fluconazole

Isavuconazonium is considered medically necessary for continued use when the individual continues to meet the initial criteria.

Initial and reauthorization is up to 12 months.

Page 1 of 3 Pharmacy Benefit Clinical Criteria: P0011 When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy.

Isavuconazonium is considered experimental, investigational, or unproven for any other use.

Note: Receipt of sample product does not satisfy any criteria requirements for coverage.

FDA Approved Indications

FDA Approved Indication Invasive Aspergillosis Cresemba® is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive aspergillosis.

Invasive Mucormycosis Cresemba is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive mucormycosis.

Usage Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

Recommended Dosing

FDA Recommended Dosing Cresemba (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug.

Table 1. Dosage Regimen for Cresemba

Loading Dose Maintenance Dosec 1 reconstituted vial (372 mga) 1 reconstituted vial CRESEMBA for Injection intravenously (372 mga) 372 mga of isavuconazonium sulfate per vial every 8 hours for 6 doses intravenously (48 hours) once daily 2 capsules (372 mga) CRESEMBA Capsules 2 capsules (372 mga) orally 186 mgb of isavuconazonium sulfate per orally every 8 hours for 6 doses capsule once daily (48 hours) a 372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole b 186 mg of isavuconazonium sulfate is equivalent to 100 mg of isavuconazole c Start maintenance doses 12 to 24 hours after the last loading dose

Switching between the intravenous and oral formulations of Cresemba is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.

With oral administration, swallow capsules whole. Do not chew, crush, dissolve, or open the capsules. Cresemba capsules can be taken with or without food.

Background

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Professional Societies/Organizations The Infectious Diseases Society of America (IDSA) [2016] recommends Cresemba as a treatment option for invasive aspergillosis and different invasive syndromes of Aspergillus (for example, invasive pulmonary aspergillosis, invasive sinus aspergillosis, aspergillosis of the central nervous system, etc). Treatment of invasive aspergillosis should be continued for a minimum of 6 to 12 weeks, depending on the degree and duration of immunosuppression, site of disease, and evidence of disease improvement. (Patterson, 2016)

The Infectious Diseases Society of America (IDSA) guidelines recommend fluconazole as initial alternative therapy for the treatment of non-neutropenic individuals with candidemia who are not critically ill and who are unlikely to have an organism resistant to fluconazole. For neutropenic individuals with candidemia, initial alternative therapy with fluconazole may be considered for clinically stable individuals who have not had prior exposure to azoles; other azoles include, itraconazole, posaconazole, and voriconazole. (Pappas, 2016)

Off Label Uses AHFS Drug Information 2020 Edition supports the following off-label uses: candida infections.

References

1. Cresemba® (package insert). Northbrook, IL: Astellas Pharma US, Inc.; December 2019. 2. McEvoy GK, ed. 2020. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2020. 3. Pappas PG, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-e50 Accessed 6/1/2020. 4. Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. Accessed 6/1/2020.

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