Date: 2018-01-08
Type of information: Granting of a Market Authorisation in the EU
Product name: Prevymis®
Compound: letermovir
Therapeutic area: Infectious diseases
Action mechanism:
Company: AiCuris (Germany) Merck & Co (USA)
Disease:
- treatment of cytomegalovirus (CMV) disease in patients with impaired cell mediated immunity deemed at risk
- prevention of HCMV (human cytomegalovirus) disease
Latest news:
- • On November 9, 2017, the FDA has approved Prevymis™ (letermovir) once-daily tablets for oral use and injection for intravenous infusion. Prevymis™ is indicated for prophylaxis (prevention) of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).
- In the pivotal Phase 3 clinical trial supporting approval, significantly fewer patients in the Prevymis™ group (38%, n=122/325) compared to the placebo group (61%, n=103/170) developed clinically significant CMV infection, discontinued treatment or had missing data through Week 24 post-HSCT [treatment difference: -23.5 (95% confidence interval -32.5 to -14.6), (p<0.0001)], the primary efficacy endpoint. All-cause mortality in patients receiving Prevymis™ was lower compared to placebo, 12% vs. 17%, respectively, at week 24 post-transplant. In this study, the incidence of bone marrow suppression in the Prevymis™ group was comparable to the placebo group. The median time to engraftment was 19 days in the Prevymis™ group and 18 days in the placebo group.
- 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 recommended dosage of Prevymis™ is 480 mg administered once daily, initiated as early as Day 0 and up to Day 28 post-transplantation (before or after engraftment), and continued through Day 100 post-transplantation. If Prevymis™ is co-administered with cyclosporine, the dosage of oral or intravenous Prevymis™ should be decreased to 240 mg once daily. Prevymis™ is available as 240 mg and 480 mg tablets, which may be administered with or without food. Prevymis™ is also available as 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over one hour.
- Prevymis™is expected to be available in December. The list price (wholesaler acquisition cost) per day for Prevymis™ tablets is $195.00 and for Prevymis™ injection is $270.00. Wholesaler acquisition costs do not include discounts that may be paid on the product.
- • On November 10, 2017, the Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation in the European Union (EU) for Prevymis® (letermovir), an antiviral medicine that prevents cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressant medicines following an allogeneic hematopoietic stem cell transplant. The CHMP recommendation is based on data from a phase III clinical trial where 570 patients who received stem cell transplants in a total of 67 trial centres in 20 countries were randomized, with 376 in the letermovir group and 194 in the placebo group. The study showed that, 24 weeks after the transplant, a lower proportion of patients in the letermovir group (37.5%) developed clinically significant CMV reactivation that was considered clinically significant, compared to the placebo group (60.6%). As always at time of approval, the orphan designation will now be reviewed to determine whether the information available to date allows maintaining letermovir’s orphan status and granting this medicine 10 years of market exclusivity
- • On January 5, 2012, Aicuris announced that AIC246 (Letermovir) has been granted Orphan Drug Designation in the US for the prevention of HCMV viremia and disease in at risk populations. This decision was made on 12 December 2011 by the FDA Office of Orphan Products Development. Letermovir has recently successfully completed a phase IIb trial for the prophylaxis of HCMV infection and disease in bone marrow transplanted patients. Results will be announced shortly.
- • On August 28, 2011, Aicuris announced that the FDA has granted Fast Track designation for AIC246 letermovir), an inhibitor of the human cytomegalovirus (HCMV).
- • On April 21, 2011, Aicuris announced that AIC246, its inhibitor against the human cytomegalovirus HCMV, currently undergoing phase IIb testing, has been granted Orphan Drug designation for the prevention of HCMV disease. This decision was made by the European Commission following the positive opinion released by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA).
- • On April 12, 2011, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion recommending letermovir for treatment of cytomegalovirus (CMV) disease in patients with impaired cell mediated immunity deemed at risk, for designation as orphan medicinal products to the European Commission.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-11-09
UE authorization: 2018-01-08
Favourable opinion UE: 2017-11-10
Favourable opinion USA:
Orphan status USA: 2011-12-12
Orphan status UE: 2012-06-06
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
