Primary endpoint results

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Clinically significant CMV infection at week 24 in HSCT patients

PREVYMIS demonstrated significant efficacy vs placebo in the primary endpoint: Clinically significant CMV infectiona at week 24 (NC=F approach)b

PREVYMIS® (letermovir) Demonstrated Clinically Significant Efficacy at Week 24

(a) Clinically significant CMV infection was defined as either the occurrence of CMV end-organ disease or initiation of anti-CMV PET, based on documented CMV viremia and the clinical condition of the patient. Viremia was determined using the Roche COBAS® AmpliPrep/COBAS TaqMan® assay; lower limit of quantification was 137 IU/mL, which is approximately 150 copies/mL.

(b) The Noncompleter=Failure (NC=F) approach was used in which patients who discontinued from the study prior to week 24 post-transplant or had a missing outcome at week 24 post-transplant were counted as failures.

(c) The categories of failure are mutually exclusive and based on the hierarchy of categories in the order listed.

(d) Through week 14, 8% of subjects in the PREVYMIS group and 39% of subjects in the placebo group experienced clinically significant CMV infection.

(e) Reasons for discontinuation included adverse event (AE), death, lost to follow-up, physician decision, and withdrawal by subject.

Rate of clinically significant CMV infection

Significantly lower rate of onset of clinically significant CMVf infection for PREVYMIS vs placebo1,g

PREVYMIS® (letermovir) Significantly Lowers the Rate of Cytomegalovirus Infection

(f) Clinically significant CMV infection was defined as either the occurrence of CMV end-organ disease or initiation of anti-CMV PET, based on documented CMV viremia and the clinical condition of the patient. Viremia was determined using the Roche COBAS® AmpliPrep/COBAS TaqMan® assay; lower limit of quantification was 137 IU/mL, which is approximately 150 copies/mL.

(g) Included patients who received at least 1 dose of study drug and excluded patients with detectable CMV DNA at baseline.

Factors associated with clinically significant CMV infection between week 14 and week 24 post-transplant among PREVYMIS patients included:

  • High-risk stratum for CMV reactivation at baseline
  • Having GVHD
  • Steroid use at any time after randomization

High- and low-risk strata

Efficacy results were consistent across high- and low-risk strata for CMV reactivation.

Efficacy Results for High-Risk CMV Reactivation
Efficacy Results for Low-Risk CMV Reactivation

Copyright © 2017 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.1

Overview of CMV-seropositive recipients [R+] status and additional risk factors at baseline

Baseline Data of CMV-Seropositive Patients in the Phase 3 Trial

Baseline data collected at randomization in the phase 3 trial.

The majority of patients in the phase 3 trial were R+ with no additional risk factors at baseline. Thirty percent of patients were R+ with ≥1 of the following additional risk factors and were placed in the high-risk stratum:

  • Related donor with human leukocyte antigen (HLA) mismatch
  • Haploidentical donor
  • Unrelated donor with HLA mismatch
  • Use of umbilical cord blood
  • Use of ex vivo T-cell–depleted grafts
  • GVHD requiring systemic corticosteroids

Reference

  1. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377(25):2433–2444.

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Indication

PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

Selected Safety Information

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.
  • The rate of adverse events occurring in at least 10% of HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • The safety and efficacy of PREVYMIS in patients below 18 years of age have not been established.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing information. The Patient information also is available.

Indication

PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV)

PREVYMIS is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT)

Selected Safety Information

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.
  • The rate of adverse events occurring in at least 10% of HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • The safety and efficacy of PREVYMIS in patients below 18 years of age have not been established.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing information. The Patient information also is available.

PREVYMIS is contraindicated in patients receiving pimozide.

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
  • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.