KIRKLAND, QC, Dec. 14, 2017 /CNW Telbec/ - Merck & Co., Inc. (NYSE: MRK), known as MSD outside Canada and the United States, announced today that the recently approved PREVYMIStm (letermovir) is expected to be available in Canada by the end of December 2017. The product is indicated for the prophylaxis of cytomegalovirus (CMV) infection in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).
CMV is a common and potentially serious viral infection in allogeneic HSCT recipients. CMV-seropositive patients who undergo an HSCT are at high risk for CMV reactivation. Any level of CMV infection is associated with increased mortality in HSCT patients.
In the pivotal Phase 3 clinical trial supporting approval, significantly fewer patients in the letermovir 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. Patients in both arms with clinically significant CMV infection were discontinued from trial and began anti-CMV therapy according to local practice. All-cause mortality in patients receiving letermovir 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 letermovir group was comparable to the placebo group. The median time to engraftment was 19 days in the letermovir group and 18 days in the placebo group.
Clinical Data Supporting Letermovir
To evaluate prophylaxis with letermovir as a preventive strategy for CMV infection in transplant recipients at high risk for CMV reactivation, the efficacy of letermovir was assessed in a multicenter, double-blind, placebo-controlled Phase 3 trial in adult CMV-seropositive recipients [R+] of an allogeneic HSCT. Patients were randomized (2:1) to receive either letermovir at a dose of 480 mg once daily adjusted to 240 mg when co-administered with cyclosporine, or placebo. Study drug was initiated after HSCT (at any time from Day 0-28 post-transplant) and continued through Week 14 post-transplant. Patients were monitored through Week 24 post-transplant for the primary efficacy endpoint, with continued follow-up through Week 48 post-transplant. The primary efficacy endpoint was the incidence of clinically significant CMV infection through Week 24 post-transplant, defined as the occurrence of either CMV end-organ disease, or initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the patient. The Non-Completer equals Failure approach was used, where patients who discontinued from the trial prior to Week 24 post-transplant or had a missing outcome at Week 24 post-transplant were counted as failures.
Among the 565 treated patients, 34% were engrafted at baseline and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndrome (15%), and lymphoma (13%). Fewer patients in the letermovir group had clinically significant CMV infection by Week 24 post-HSCT compared to the placebo group, 18% vs. 42%, respectively. At Week 14 post-transplant, the Kaplan-Meier (K-M) event rate for clinically significant CMV infection was 6.8% in the letermovir group compared to 41.3% in the placebo group. Letermovir demonstrated significant benefit compared to placebo in time to clinically significant CMV infection through Week 24 post-HSCT (18.9% vs. 44.3% cumulative rate; stratified log-rank test, two-sided p-value <0.0001).
Efficacy consistently favoured letermovir across subgroups including low and high risk for CMV reactivation, stem cell source, donor mismatch, haploidentical transplant, conditioning regimens, and concomitant immunosuppressive regimens.
Post-hoc analysis demonstrated that among PREVYMIS-treated patients, inclusion in the high-risk stratum for CMV reactivation at baseline, occurrence of graft-versus-host disease (GVHD), and steroid use at any time after randomization may be associated with the development of clinically significant CMV infection between Week 14 and Week 24 post-transplant.
The Kaplan-Meier event rate for all-cause mortality in the PREVYMIS vs. placebo groups was 12% vs. 17% at Week 24 post-transplant, and 24% vs. 28% at Week 48 post-transplant. The most commonly reported adverse reactions occurring in at least 1% of subjects in the letermovir group through Week 24 post-transplant and at a frequency greater than placebo were: nausea, diarrhea, and vomiting.
About PREVYMIS (letermovir)
PREVYMIS is a member of a new class of non-nucleoside CMV inhibitors (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. 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). For more information, please consult the Canadian PREVYMIS (letermovir) product monograph here.
About CMV and Treatment
CMV is a common virus that infects people of all ages. Many adults in Canada 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.
For over a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer's disease and infectious diseases including HIV and Ebola.
This news release of Merck & Co., Inc., Kenilworth, 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 products that the products 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 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 2016 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).
*Please consult the Canadian PREVYMIS (letermovir) product monograph here.
SOURCE Merck Canada Inc.
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