Coverage Policy Manual
Policy #: 2018004
Category: Pharmacy
Initiated: February 2018
Last Review: February 2019
  Letermovir (Prevymis)

Description:
Letermovir is a CMV terminase complex inhibitor (Clinical Pharmacology [Internet], 2017).
 
Letermovir is given intravenously or as an oral medication.  This policy refers to the intravenous form, and the oral form will be processed under the pharmacy benefit.
 
Letermovir (Prevymis™) was FDA approved in 2017 for the prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients (R+) of an allogeneic hematopoietic stem cell transplant (HSCT) (FDA, 2017).

Policy/
Coverage:
Effective February 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Letermovir meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indication:
      • Patients receiving allogeneic hematopoietic stem cell transplant who:
          • Have documented CMV seropositivity within 1 year prior to hematopoietic stem cell transplant AND
          • Letermovir is being started between day 0 and Day 28 post-transplant.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Dosing and Administration
Dosing must be within FDA guidelines of 480 mg once daily through 100 days post-transplant.  This should be decreased to 240mg if co-administered with cyclosporine.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary
Coverage Criteria
 
Letermovir does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for all other indications.
 
For members with contracts without primary coverage criteria, Letermovir is considered investigational for all other indications. Investigational services are specific contract exclusions in
most member benefit certificates of coverage.
 
Effective February 2018 to January 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Letermovir meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indication:
    • Patients receiving allogeneic hematopoietic stem cell transplant who:
        • Have documented CMV seropositivity within 1 year prior to hematopoietic stem cell transplant AND
        • Letermovir is being started between day 0 and Day 28 post-transplant.
 
Dosing must be within FDA guidelines of 480 mg  once daily through 100 days post-transplant.  This should be decreased to 240mg if co-administered with cyclosporine.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary
Coverage Criteria
 
Letermovir does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for all other indications.
 
For members with contracts without primary coverage criteria, Letermovir is considered investigational for all other indications. Investigational services are specific contract exclusions in
most member benefit certificates of coverage.

Rationale:
The safety and efficacy of letermovir was evaluated in a multicenter, double-blind, placebo- controlled trial in which patients where randomized to either letermovir or placebo.  Randomization was stratified by investigational site and risk level for CMV reactivation at the time of study entry.  Letermovir patients received either 480mg once daily or 240mg once daily if administered with cyclosporine, and was initiated at any time between Day 0 and Day 28 post-transplant. Treatment continued through week 14 post-transplant.  CMV DNA was monitored weekly through week 14 post-transplant, then twice-weekly though week 24.  Patients who had CMV viremia prior to study drug initiation were excluded.  In total, 325 patients received letermovir and 170 received placebo.  The primary endpoint was the incidence of clinically significant CMV infection through week 24 post-transplant, which would indicate prophylaxis failure.  Clinically significant CMV infection was defined as the occurrence of either CMV end-organ disease or initiation of anti-CMV preemptive therapy  based on documented CMV viremia. Pre-emptive therapy was initiated based on a risk-stratified protocol, in which patients received preemptive therapy if they had CMV DNA above a certain threshold (>150 copies/ml for the high risk group or 300 copies/ml for the low risk group for the first 14 weeks then >300 copies/ml for either group during weeks 15-24).  Overall, 38% failed prophylaxis in the letermovir group, as opposed to 61% of the placebo group (p<0.0001).  The Kaplan- Meier event rate for all-cause mortality was 12% in the letermovir group as opposed to 17% in the placebo group at week 24 post-transplant, and was 24% in the letermovir group as opposed to 28% in the placebo group at week 48.
 
2019 Update
A literature search conducted through January 2019 did not reveal any new information that would prompt a change in the coverage statement.

CPT/HCPCS:
J3490Unclassified drugs

References: Clinical Pharmacology [Internet].(2017) Letermovir. Elsevier. c2017- [cited 2017 December 18]. Available from: http://www.clinicalpharmacology.com

Marty FM, Ljungman P, Chemaly RF, et al.(2017) Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017.

U.S. Food and Drug Administration (FDA).(2017) Letermovir. Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939orig1s000,209940orig1s000lbl.pdf. Last accessed Feb. 06, 2018.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.