dm+d

36611011000001100

New Medicines

PrevymisProphylaxis of cytomegalovirus (CMV) reactivation and disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant (HSCT)

Information

Prevymis
New molecular entity
Merck Sharp & Dohme (MSD)
Merck & Co, Inc.

Development and Regulatory status

Launched
Launched
Launched
January 2019
Yes
Yes
Oct 20Prevymis infusion launched in the UK. Price 240mg/12ml conc for soln for inf in vial, 1=£146.27 [23].
Jan 19Prevymis tablets price: £3723.16 per 28 day pack [22]
Jan 19Prevymis tablets launched in the UK in Jan 19. Prevymis intravenous still not launched [21].
Jan 19Prevymis was launched in Germany in Feb 18 [20].
Jan 19Has been available in US since Dec 17 [19].
Jul 18NICE scope notes that STA suspended on manufacturers request because it is considering its commercial arrangement for this product. Appraisal committee meeting will be rescheduled [18].
Jan 18MA granted throughout EU by the EMA on 8th Jan 2018 [17].
Nov 17CHMP recommends approval in EU for prophylaxis of cytomegalovirus (CMV) reactivation and disease in adult CMV-seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant (HSCT) [15].
Nov 17Approved in the US. Launch expected Dec 17 with a list price of $195 per day for the tablet formulation and $270 per day for the injectable which equates to $19,500, or $27,000 per 100-day treatment course [14].
Aug 17Has also been filed in US [13].
May 17Filed in EU via the centralised procedure and is being reviewed under the accelerated assessment programme [12].
Feb 17EU & US filings planned for 2017 [11].
Oct 15PIII development continues [9].
Jun 12Granted orphan drug status in the EU [5].
Feb 12On the basis of encouraging PII efficacy & safety results, AiCuris announce they are preparing PIII development [4].
Jan 12Granted orphan drug status in the US [2].
Aug 11Granted fast track status in the US [1].

Category

Non-nucleosidic human cytomegalovirus replication inhibitor
Human cytomegalovirus is the most common virus pathogen in solid organ transplant recipients (kidney, heart, liver, lung and pancreas) and bone marrow transplant recipients. It is the major cause of morbidity and mortality during the first 6 months after transplantation. Newborn babies are also susceptible. The number of patients with impaired cell-mediated immunity at risk of CMV disease is ~ 3.1 people in 10,000 in the EU - equivalent to ~ 157,000 people.
Prophylaxis of cytomegalovirus (CMV) reactivation and disease in adult CMV-seropositive recipients of an allogeneic haematopoietic stem cell transplant (HSCT)
Oral

Further information

Yes

Trial or other data

Dec 17 Results of NCT02137772 published in NEJM. RCT (n=565) found letermovir prophylaxis resulted in significantly lower risk of clinically significant CMV infection vs. placebo by week 24 after transplantation (122/325 [37.5%] vs.103/170 [60.6%], p<0.001). Frequency/severity of adverse events were similar in two groups overall [16].
Feb 17Merck announces that as well as reducing infections in a trial involving bone marrow transplant patients, letermovir also reduced patient deaths. The results showed that 37.5% of patients treated with letermovir developed CMV by week 24, compared to 60.6% for a matched placebo group. It also led to lower all-cause mortality at 24 weeks, at 9.8% compared to 15.9% for placebo [11].
Oct 16Merck announces letermovir met its primary endpoint of reducing the percentage of participants with clinically significant CMV infection through 24 weeks after transplant in a PIII trial [10].
Mar 15NCT02137772 is a global PIII randomized, placebo-controlled trial of letermovir for the prevention of clinically significant human cytomegalovirus (CMV) infection in 540 adult, CMV-seropositive allogeneic hematopoietic stem cell transplant recipients, up to 24 weeks after transplant. The study started in Jun 14 and is due to complete Jul 17 [8].
May 14PII study (NCT01063829; n=131) published in NEJM. The reduction in the incidence of all-cause prophylaxis failure was dose-dependent. The incidence of prophylaxis failure with letermovir, as compared with placebo, was 48% versus 64% at a daily letermovir dose of 60 mg (P=0.32), 32% at a dose of 120 mg (P=0.01), and 29% at a dose of 240 mg (P=0.007). Kaplan–Meier time-to-onset profiles for prophylaxis failure showed a significant difference in the comparison of letermovir at a dose of 240 mg per day with placebo (P=0.002). The safety profile of letermovir was similar to placebo, with no indication of hematologic toxicity or nephrotoxicity [7].
Oct 12Merck and AiCuris have entered into an exclusive worldwide licensing agreement for letermovir (AIC246), which is being investigated for the treatment and prevention of HCMV infection in transplant recipients [6].
Feb 12Company report positive results from its PII study that included 133 HCMV-seropositive allogeneic human blood precursor cell (HBPC) recipients. Compared to placebo, letermovir, 120 mg and 240mg once daily for 84 days met both primary efficacy endpoints (incidence and time to onset of ‘HCMV prophylaxis failure’ defined as development of systemic detectable HCMV replication - viral load above >42 DNA copies/ml - or HCMV end-organ disease) . In the primary Full Analysis Population, the incidence of failure was: placebo (63.6%), letermovir 240mg/day (29.4%; p=0.007) and 120mg/day (32.3%; p=0.014). HCMV prophylaxis failure among patients receiving treatment for at least 7 days prior to HCMV replication occurred in 0 patients on letermovir 240mg (p=0.004 vs. placebo) and 2 patients on 120mg (p=0.109 vs. placebo). Time to onset of prophylaxis failure was significantly different with the higher dose (p=0.02) vs placebo. Treatment emergent adverse events considered related to the treatment or leading to discontinuation of treatment was lower in those receiving letermovir (17.3% and 25.5%, respectively) than placebo (33.3% and 57.6%, respectively) [3].
Aug 11Letermovir is currently being evaluated in an international PIIb trial results of which are expected by the end of 2011. Letermovir appears to have no clinically significant drug-drug interactions when co-administered with immunosuppressive drugs [1].

Evidence based evaluations

PrevymisProphylaxis of cytomegalovirus (CMV) infections in kidney transplant patients

Information

Prevymis
Licence extension / variation
Merck Sharp & Dohme (MSD)
Merck & Co (name used in US for MSD)

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Non-nucleosidic human cytomegalovirus replication inhibitor
Human cytomegalovirus is the most common virus pathogen in solid organ transplant recipients (kidney, heart, liver, lung and pancreas) and bone marrow transplant recipients. It is the major cause of morbidity and mortality during the first 6 months after transplantation. The number of patients with impaired cell-mediated immunity at risk of CMV disease is ~ 3.1 people in 10,000 in the EU - equivalent to ~ 157,000 people.
Prophylaxis of cytomegalovirus (CMV) infections in kidney transplant patients
Oral