Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Letermovir · 9 trials · 11 indications
To test the hypothesis that letermovir will be associated with reduced incidence of recurrent viremia, recurrence will be measured defined as incidence of any cytomegalovirus replication greater than 1000 IU/mL requiring treatment after withdrawal of secondary prophylaxis.
To test the hypothesis that letermovir will be associated with reduced duration of (val)ganciclovir treatment, the duration of VGC treatment will be measured.
Clinically significant CMV infection was defined as either one of the following: 1) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant or 2) onset of CMV end-organ disease. The percentage of participants with clinically significant CMV infection up to week 24 post-transplant is reported.
Percentage of participants with one or more adverse events (AEs)
Percentage of participants who discontinued from study drug due to an AE
Clinically significant CMV infection is either the onset of probable or proven CMV end-organ disease or initiation of anti-CMV preemptive therapy (PET) with approved anti-CMV agents (ganciclovir, valganciclovir, foscarnet, and/or cidofovir) based on documented CMV viremia and the clinical condition of the participant. Missing values were handled by the observed failure (OF) approach where failure was defined as all participants who develop clinically significant CMV infection or discontinue prematurely from the study with CMV viremia from week 14 (\~100 days) through week 28 post-transplant. It was hypothesized that LET is superior to placebo in the prevention of clinically significant CMV infection when LET prophylaxis is extended from 100 to 200 days.
CMV disease was defined as the presence of either CMV end-organ disease or CMV syndrome and was confirmed by an independent, blinded Clinical Adjudication Committee (CAC). Only CAC-confirmed ("adjudicated") cases were included in percentage of participants who met the endpoint. Investigator-assessed cases which were not confirmed by the CAC were not included.
Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with clinically-significant CMV infection was assessed.
The primary outcome will be CMV infection (CMV viremia with CMV viral load \>1,000, CMV syndrome, or tissue invasive CMV disease) during the planned prophylaxis period and the following 180 days
The primary outcome will be the proportion of days during which appropriately-dosed prophylaxis was received during the planned treatment course.
Number of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease during letermovir prophylaxis.
Number of lung transplant recipients with idiopathic pulmonary fibrosis with CMV infection or disease in the 3 months following completion of prophylaxis with letermovir.
Blood samples will be collected at multiple time points to estimate AUC0-24
| Arm | Type | Description |
|---|---|---|
| Letermovir for CMV in Transplant Patients | EXPERIMENTAL | Enrolled participants will be converted from treatment with ganciclovir derivatives to letermovir |
| Letermovir | EXPERIMENTAL | Chinese HSCT recipients will receive 240 mg of Letermovir \[for participants on Cyclosporin A (CsA)\] or 480 mg of Letermovir (for participants not on CsA) either orally or IV once daily through week 14 (\~100 days) post-transplant. |
| Placebo | PLACEBO_COMPARATOR | Participants who received HSCT transplant and 100 days of LET prophylaxis were randomized to an additional 100 days of placebo treatment. |
| Valganciclovir | ACTIVE_COMPARATOR | 900 mg VGCV tablet orally, once daily; placebo to LET tablet orally once daily; and placebo to ACV orally every 12 hours for 28 weeks |
| Weight-banded letermovir dosing | EXPERIMENTAL | Participants who are between 4 and 52 weeks post-KT will receive letermovir for 7 consecutive days. |
| Name | Type | Description |
|---|---|---|
| Letermovir | DRUG | 480 mg taken orally once daily, for 84 days |
| Letermovir tablet | DRUG | A single 240 mg tablet or two 240 mg tablets letermovir administered orally, once daily for 28 weeks |
| Letermovir IV | DRUG | IV solution of 240 mg (one vial) or 480 mg (2 vials) letermovir in 250 mL infused over 60 minutes, once daily for 28 weeks |
| Placebo | DRUG | Placebo was administered as tablets matched to LET or as inactive (saline or dextrose) intravenous infusion. |
| Valganciclovir | DRUG | 900 mg VGCV tablet orally, once daily for 28 weeks |
| Acyclovir (ACV) | DRUG | 400 mg over-encapsulated ACV tablet orally, every 12 hours for 28 weeks |
| Placebo to ACV | DRUG | Over-encapsulated placebo tablet orally, every 12 hours for 28 weeks |
| Placebo to LET | DRUG | Placebo to LET tablet orally, once daily for 28 weeks |
| Placebo to VGCV | DRUG | Placebo to VGCV tablet orally, once daily for 28 weeks |
| Letermovir 480 MG [Prevymis] | DRUG | Letermovir for CMV prophylaxis in thoracic organ transplant recipients. Letermovir will be administered by oral administration, as per study protocol. The intended duration of therapy will be up to 365 days, depending on organ transplanted and donor and recipient CMV status. However, treatment may discontinued as discussed in Section 7. Letermovir is dosed at 480mg daily for patients with CrCl \>10. Dose adjustment, as per package insert, is recommended in setting of co-administration of cyclosporine, with dose reduction of letermovir to 240mg daily. Missed doses of letermovir will not be made up. |
Inclusion Criteria: * undergone kidney or simultaneous kidney/pancreas transplant * high-risk CMV serostatus (D+/R-) at time of transplant * develop CMV viremia that necessitates treatment per our institutional protocol (enrolled in the CMV stewardship monitoring initiative) * demonstrate proven or...
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Letermovir is an investigational small molecule being studied for the prevention of cytomegalovirus (CMV) infection and disease in high-risk transplant populations, including allogeneic hematopoietic stem cell transplant recipients, kidney transplant recipients, and lung transplant patients. It is being developed by Merck & Company, Inc. (MRK).
Letermovir targets the CMV terminase complex, inhibiting viral DNA processing and packaging. This mechanism prevents the replication of cytomegalovirus, reducing the risk of clinically significant CMV infection and disease in transplant recipients.
Letermovir is being developed by Merck & Company, Inc., a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol MRK. Merck is conducting Phase 3 clinical trials to evaluate the drug's safety and efficacy in preventing CMV infection and disease.
Letermovir is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Multiple Phase 3 trials are completed, studying its use in preventing CMV infection in hematopoietic stem cell transplant and kidney transplant recipients.
Letermovir has been studied in several clinical trials, including NCT02137772, a Phase 3 trial in CMV-seropositive allogeneic hematopoietic stem cell transplant recipients; NCT03930615, an extension study from Day 100 to Day 200 post-transplant; and NCT04129398, a Phase 3 trial in Japanese kidney transplant recipients. These trials are completed.
Yes, Letermovir is also known as Letermovir 480 MG [Prevymis]. Prevymis is a brand name associated with this drug, which is being developed by Merck & Company, Inc. for the prevention of cytomegalovirus infection and disease.