Letermovir granted marketing authorisation as an orphan medicinal product

MSD has announced that the European Commission (EC) has granted marketing authorisation for letermovir as an orphan medicinal product for prophylaxis (prevention) of cytomegalovirus (CMV) reactivation and disease in adult CMV-seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant (HSCT).¹

Approximately 50-80% of adults in the UK are thought to be infected with CMV, and once infected it can persist in the body as an inactive or latent state.2 It can become reactivated if the immune system is compromised, for example, if a patient is taking immunosuppressant medication as part of a HSCT regimen.³ HSCT can be a life-saving treatment for more than 70 different diseases including leukaemia, lymphoma, sickle cell anaemia.⁴ CMV infection is a common clinically significant complication in these patients and reactivation after transplant is associated with serious complications and increased mortality.⁵ Letermovir is a first-in-class antiviral drug that inhibits CMV replication.⁶

Professor Karl Peggs, Honorary Consultant in Haematology/Transplantation at UCL Hospitals, comments “Cytomegalovirus remains a major clinical challenge following allogeneic transplantation, and current treatment strategies remain both toxic and burdensome to patients. Any new therapy that can reduce this burden will be welcomed by both physicians and patients, so the licensing of letermovir represents an important step forward in the field.“

The EC decision was based on data from a Phase III clinical trial where 565 patients who received stem cell transplants in a total of 67 trial centres in 20 countries were randomised and treated, with 373 in the letermovir group and 192 in the placebo group based on a 2:1 randomisation.⁶ The study primary endpoint showed that, 24 weeks after the transplant, a lower proportion of patients in the letermovir group (37.5%) developed clinically significant CMV infection that was statistically significant, compared to the placebo group (60.6%).^1,2

MSD is now working closely and collaboratively with NHS policy-makers, NICE, SMC and other stakeholders to help ensure that letermovir is made available to patients in the UK as rapidly as possible.

Louise Houson, UK Managing Director, MSD said; “MSD is delighted that the EC has recognised the potential of letermovir for prophylaxis of cytomegalovirus (CMV) reactivation in certain patients in need of a new option. This authorisation brings us a step closer to making letermovir available in the UK and we will continue to work closely with NICE, NHS, SMC and other relevant stakeholders to help ensure that appropriate patients have access to letermovir as soon as possible.“

In the Phase III clinical trial supporting EC authorisation, the most commonly reported adverse reactions occurring in at least 1% of patients in the letermovir group and at a frequency greater than placebo were: nausea (7.2%), diarrhoea (2.4%), and vomiting (1.9%).1 The most frequently reported adverse reactions that led to discontinuation of letermovir were nausea (1.6%), vomiting (0.8%), and abdominal pain (0.5%).¹

EC authorisation of letermovir allows for marketing in all 28 European Union (EU) member states, as well as European Economic Area members, Iceland, Liechtenstein and Norway. Letermovir was authorised in the United States by the US Food and Drug Administration in November 2017.

References

1. EMA, Letermovir SmPC. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Info… [Accessed 25th Jan 2018]
2. Nhsdirect.wales.nhs.uk. (2018). NHS Direct Wales – Encyclopaedia: Cytomegalovirus. [online] Available at: http://www.nhsdirect.wales.nhs.uk/encyclopaedia/c/article/cytomegalovirus/ [Accessed 11 Jan. 2018].
3. National Institute for Health Research. (2016) Letermovir for the prevention of cytomegalovirus infection in sero-positive patients undergoing allogenic haematopoietic stem cell transplantation. Pp.3. Available at: http://www.io.nihr.ac.uk/wp-content/uploads/migrated/Letermovir-April-20…. [Accessed 11 Jan. 2018].
4. National Marrow Donor Program (2017). [online] Available at: https://www.wbmt.org/fileadmin/pdf/01_General/One_Million_Transplants_Fa…. [Accessed 15 Jan. 2018].
5. Nice.org.uk. (2017).[online] Available at: https://www.nice.org.uk/guidance/gid-ta10195/documents/draft-scope-pre-r…
6. Marty, F. et al (2017). Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. New England Journal of Medicine, 377(25), pp.2433-2444.