Merck Receives Positive EU CHMP Opinion for PREVYMIS® for Prevention of CMV Disease in High-Risk Adult Kidney Transplant Recipients and Extended 200-Day Dosing in Adult HSCT Recipients at Risk for Late CMV Infection and Disease

Rhea-AI Summary

Merck's PREVYMIS receives positive recommendation from CHMP for the prevention of CMV disease in kidney transplant recipients and extended dosing for HSCT recipients.

Positive

• The Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of PREVYMIS for preventing CMV disease in high-risk kidney transplant recipients.
• The CHMP also recommended extending dosing for PREVYMIS from 100 days to 200 days for adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT) who are at risk for late CMV infection and disease.

Negative

• None.

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of PREVYMIS^® (letermovir) for prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (Donor CMV-seropositive/Recipient CMV-seronegative [D+/R-]). The CHMP has also recommended the approval for extending dosing for PREVYMIS from 100 days to 200 days following transplant in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT) who are at risk for late CMV infection and disease. The CHMP’s recommendations will now be reviewed by the European Commission for marketing authorization in the European Union (EU) and a final decision is expected this year.

“This positive CHMP opinion is an important step towards making PREVYMIS available to high-risk kidney transplant patients to help prevent CMV disease, as well as extending dosing to 200 days for adults who receive an allogeneic stem-cell transplant and are at risk for late CMV infection and disease,” said Dr. Elizabeth Rhee, vice president, global clinical development, Merck Research Laboratories. “CMV is a potentially serious viral infection for these high-risk transplant recipients, and we are pleased that these patients in the EU will soon be able to access PREVYMIS to help prevent CMV infection and disease.”

PREVYMIS is an antiviral agent that was initially approved by the U.S. Food and Drug Administration (FDA) in 2017 and by the EMA in 2018 for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic HSCT. In June 2023, the FDA approved PREVYMIS for prophylaxis of CMV disease in adult kidney transplant recipients at high risk, and in August 2023, the FDA approved extended 200-day dosing for PREVYMIS for CMV prophylaxis in HSCT recipients at risk for late CMV infection and disease.

The CHMP opinion for use of PREVYMIS for CMV disease prophylaxis in adult kidney transplant recipients was supported by a Phase 3, randomized, multicenter, double-blind, active comparator-controlled non-inferiority trial (P002, NCT03443869) in 589 adult kidney transplant recipients at high risk (CMV D+/R-). Additionally, the efficacy of extending PREVYMIS prophylaxis from Week 14 (~100 days) through Week 28 (~200 days) post-HSCT in patients at risk for late CMV infection and disease was assessed in a multicenter, double-blind, placebo-controlled Phase 3 trial (P040, NCT03930615) in adult CMV-seropositive recipients [R+] of an allogeneic HSCT.

About CMV

Globally, many adults are CMV-seropositive [R+], meaning they have CMV antibodies in their blood, indicating a previous exposure to or primary infection with CMV. People with healthy immune systems rarely develop CMV symptoms after initial infection, with the virus typically remaining inactive or latent in the body for life. CMV-seropositive [R+] patients who undergo an HSCT are at high risk for CMV reactivation. CMV‐seronegative recipients who receive an organ from a CMV‐seropositive donor [D+/R-] are at high risk of CMV disease after transplantation.

Selected Safety Information about PREVYMIS

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 concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.

The rate of adverse events occurring in at least 10% of HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo 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%).

Hypersensitivity reaction, with associated moderate dyspnea, occurred in one HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.

The most common adverse event occurring in at least 10% of kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).

If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.

Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.

Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.

PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.

The safety and efficacy of PREVYMIS in patients below 18 years of age have not been established.

For patients with CLcr greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Following the completion of PREVYMIS prophylaxis, monitoring for CMV reactivation in HSCT recipients is recommended.

About PREVYMIS (letermovir)

PREVYMIS inhibits viral replication by targeting the CMV DNA terminase complex. Since 2017, PREVYMIS has been the only drug approved in the United States for prophylaxis of CMV infection and disease in adults who are CMV-seropositive [R+] and have received an allogeneic HSCT and has also been approved for this indication in more than 60 countries including EU member states, Canada, Japan and China. PREVYMIS is also approved in the United States for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV-seropositive/Recipient CMV-seronegative [D+/R-]). 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 Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2022 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for PREVYMIS at https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_pi.pdf and Patient Information/Medication Guide for PREVYMIS at https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_ppi.pdf.

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Source: Merck & Co., Inc.

FAQ

What is the recommendation from the CHMP for PREVYMIS?

The CHMP has recommended the approval of PREVYMIS for preventing CMV disease in high-risk kidney transplant recipients and extending dosing for adult CMV-seropositive recipients of an allogeneic HSCT who are at risk for late CMV infection and disease.

When will the final decision for marketing authorization be made?

A final decision is expected to be made this year.

What is the significance of this recommendation for high-risk kidney transplant patients?

This recommendation is an important step towards making PREVYMIS available to high-risk kidney transplant patients to help prevent CMV disease.

What is the significance of this recommendation for adult CMV-seropositive recipients of an allogeneic HSCT?

This recommendation extends the dosing of PREVYMIS from 100 days to 200 days for adult CMV-seropositive recipients of an allogeneic HSCT who are at risk for late CMV infection and disease.