PREVYMIS™ in Preventing Cytomegalovirus Infection and Disease in Adults Undergoing Allogeneic HCT

Merck, known as MSD outside the United States and Canada, announced today the presentation of findings from a systematic literature review and meta-analysis of data from real-world observational studies of PREVYMIS™ (letermovir) for primary prophylaxis (prevention) of cytomegalovirus (CMV) infection and disease in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) who were CMV-seropositive. In the analysis of 48 real-world observational studies, compared to controls (mostly preemptive therapy), primary prophylaxis with PREVYMIS was associated at 100 days of follow-up after alloHCT with: 87% lower odds of CMV reactivation (N=3,054 across 18 studies; Pooled Odds Ratio (POR)=0.13, [95% CI, 0.08, 0.22]); 91% lower odds for clinically significant CMV infection (N=3,993 across 21 studies; POR=0.09, [95% CI, 0.05, 0.14]); 69% lower odds of CMV disease (N=1,838 across 10 studies; POR=0.31, [95% CI, 0.12, 0.77]); 94% lower odds of CMV-related hospitalization (N=905 across 2 studies; POR=0.06, [95% CI, 0.01, 0.28]); and 48% lower odds of Grade 2 or greater graft versus host disease (GvHD) (N=471 across 6 studies; POR=0.52, [95% CI, 0.32, 0.86]). Consistent results were observed at 200 days of follow-up with respect to CMV reactivation, clinically significant CMV infection, and CMV disease. See additional results below. The findings were presented during an oral session at the European Society for Blood and Marrow Transplantation (EBMT) 48th Annual Meeting (Abstract #OS04-07).

Patients undergoing alloHCT who are CMV-seropositive [R+] are at high risk for CMV reactivation. CMV infection is a common clinically significant complication in these patients and early CMV reactivation after alloHCT is associated with increased mortality. PREVYMIS is a first-in-class antiviral agent that was approved by the U.S. Food and Drug Administration in 2017 and is indicated for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

“CMV reactivation in patients who undergo alloHCT can lead to potentially serious health complications,” said Dr. Roy Chemaly, director, Clinical Virology Research Program at the University of Texas MD Anderson Cancer Center. “This analysis of real-world effectiveness of letermovir builds upon the evidence from the Phase 3 clinical trial in which letermovir as prophylaxis reduced the risk of CMV infection in CMV-seropositive patients. This new analysis also provides data on the potential of letermovir to reduce the odds of CMV-related hospitalization and graft versus host disease.

Real-World Outcomes for Primary Prophylaxis of CMV Infection and Disease Using PREVYMIS

The objective of the analysis was to assess the effectiveness of primary prophylaxis with PREVYMIS among adults undergoing alloHCT using systematic literature review and meta-analysis of data from real-world observational studies. An initial search of peer-reviewed publications via PubMed and Embase and relevant conference proceedings through October 2021 identified 576 records. Further screening to identify publications that met the pre-specified inclusion criteria yielded 48 distinct studies (22 full publications and 26 conference proceedings) that reported on outcomes of PREVYMIS for primary prophylaxis in patients undergoing alloHCT. These studies involved patients predominantly in the United States, Italy, and Japan and employed a range of timepoints for initiation of PREVYMIS post-transplant (0 – 42 days) and duration of therapy (79 – 191 days). Forty of the 48 studies were comparator studies and, in all but one study, the control was preemptive therapy; the other eight studies were single-arm studies.

About PREVYMIS (letermovir)

PREVYMIS is the only drug approved in the United States for prophylaxis of CMV infection and disease in adults who are CMV-seropositive and have received an allogeneic HSCT. PREVYMIS is also approved in more than 50 countries outside of the United States, including EU member states, Canada, Japan and China. PREVYMIS is a first-in-class non-nucleoside CMV inhibitor (3,4 dihydro-quinazolines) and inhibits viral replication by specifically targeting the viral terminase complex. Cross resistance is not likely with drugs outside of this class. PREVYMIS is fully active against viral populations with substitutions conferring resistance to CMV DNA polymerase inhibitors. These DNA polymerase inhibitors are fully active against viral populations with substitutions conferring resistance to PREVYMIS. PREVYMIS has no activity against other viruses.

Under an agreement signed in 2012, Merck (through a subsidiary) purchased worldwide rights to develop and commercialize letermovir from AiCuris GmbH & Co KG (www.aicuris.com).

About CMV and Treatment

CMV is a common virus that infects people of all ages. Many adults in the United States are CMV seropositive, meaning they have CMV antibodies in their blood, indicating a previous exposure to or primary infection with CMV. People with normal immune systems rarely develop CMV symptoms after initial infection, with the virus typically remaining inactive or latent in the body for life. A weakened immune system may give the virus a chance to reactivate, potentially leading to symptomatic disease or a secondary infection due to other pathogens. CMV disease can lead to end-organ damage, including gastrointestinal tract disease, pneumonia or retinitis. Transplant recipients who develop CMV infection post-transplant are at increased risk for transplant failure and death. CMV prophylaxis with certain existing antivirals has been associated with drug-specific effects, including myelosuppression and renal toxicity, in HSCT recipients.

About Merck

For over 130 years, Merck, known as MSD outside the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world.

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