User login
The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).
Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.
“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.
Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)
The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.
Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.
For more details on letermovir, see the full prescribing information.
Trial results
The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) 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%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
Results from this trial were presented at the 2017 BMT Tandem Meetings. 
The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).
Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.
“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.
Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)
The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.
Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.
For more details on letermovir, see the full prescribing information.
Trial results
The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) 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%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
Results from this trial were presented at the 2017 BMT Tandem Meetings.
The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).
Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.
“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.
Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)
The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.
Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.
For more details on letermovir, see the full prescribing information.
Trial results
The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) 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%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
Results from this trial were presented at the 2017 BMT Tandem Meetings.