News Release
News Release ____________________________________________________________________________________ Media Contact: Investor Contact: Annick Robinson 438-837-2550 [email protected] Justin Holko +1 908-423-5088 [email protected] HEALTH CANADA APPROVES MERCK’S POSANOL® (POSACONAZOLE) SOLUTION FOR INJECTION, A NEW INTRAVENOUS FORMULATION Kirkland, Quebec – November 13, 2014 – Merck, known as MSD outside of Canada and the United States, today announced that Health Canada has approved POSANOL® (posaconazole) Solution for Injection 300 mg/vial, a new intravenous (IV) formulation. POSANOL is also approved in Canada in two formulations for oral administration: POSANOL Delayed-Release Tablets 100 mg, and POSANOL Oral Suspension 40 mg/mL. POSANOL Solution for Injection is expected to be available as early as the end of November, 2014. Invasive fungal infections are a major cause of morbidity and mortality, in particular among patients who are severely immunocompromised such as patients receiving chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) and hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose immunosuppressive therapy for graft versus host disease (GVHD). Mortality rates from aspergillosis have been reported to be at least 50% in patients with neutropenia and 86% in patients who have undergone hematopoietic stem cell transplant.1 "With the approval of posaconazole for intravenous use, we now have a choice of three formulations to help meet different patient needs,” said Dr. Michel Laverdière, Infectious Disease Specialist at Maisonneuve Rosemont Hospital. "This new IV formulation will facilitate the management of patients unable to take medications orally, for example patients affected by vomiting, mucositis, or diarrhea.” POSANOL® is a Registered trademark of MSD International Holdings GmbH. Used under license. -2“The addition of this new IV formulation to the POSANOL family of products provides an additional option to patients who need prophylaxis of Aspergillus and Candida infections or treatment of invasive aspergillosis that is refractory to amphotericin B or itraconazole. This addition follows the recent approval in May 2014 of the POSANOL delayed-release tablets, a new oral formulation offering the antifungal efficacy of POSANOL oral suspension with an enhanced pharmacokinetic profile and once-daily dosing after twice-daily dosing on the first day,” said Dr. Mauricio Ede, Executive Director, Medical Affairs. Approval of POSANOL (posaconazole) Solution for Injection based on a pharmacokinetic study in patients The approval for POSANOL Solution for Injection was supported by the results of a noncomparative multicenter study performed to evaluate the pharmacokinetic properties, safety and tolerability of this new formulation. The study2 was conducted in a similar patient population to that previously studied in the pivotal posaconazole oral suspension clinical program: patients with AML or MDS who had recently received chemotherapy and had developed or were anticipated to develop significant neutropenia, or patients who had undergone HSCT and were receiving immunosuppressive therapy for prevention or treatment of GVHD. In clinical trials, the adverse reactions reported for POSANOL Solution for Injection were generally similar in type to that reported in trials of POSANOL Oral Suspension. The most frequently reported adverse reactions with an onset during the posaconazole intravenous phase of dosing 300 mg once-daily therapy were diarrhea (32%), hypokalemia (22%), fever (21%) and nausea (19%). Approval of POSANOL (posaconazole) Delayed-Release Tablets based on a pharmacokinetic study in patients The approval for POSANOL Delayed-Release Tablets was supported by the results of a non-comparative multicenter study performed to evaluate the pharmacokinetic properties, safety and tolerability of posaconazole delayed-release tablets. The study2 was conducted in a similar patient population as that previously studied in the pivotal posaconazole oral suspension clinical program. -3In clinical trials, the most frequently reported adverse reactions with POSANOL DelayedRelease Tablets were diarrhea, fever and nausea. The type of adverse reactions reported for POSANOL Delayed-Release Tablets were generally similar to that reported in trials of POSANOL Oral Suspension. Clinical experience with POSANOL (posaconazole) oral suspension Two randomised, controlled clinical studies were conducted using posaconazole oral suspension as prophylaxis for the prevention of invasive fungal infections among patients at high risk3-4. Both studies demonstrated fewer breakthrough infections caused by Aspergillus species in patients receiving posaconazole prophylaxis when compared to patients receiving fluconazole or itraconazole. A third study was conducted using posaconazole oral suspension for the treatment of invasive aspergillosis in patients with disease refractory to conventional antifungal therapy or in patients intolerant of these medicinal products5. In one randomized, open-label study that compared posaconazole oral suspension (200 mg three times a day) with fluconazole suspension (400 mg once daily) or itraconazole oral solution (200 mg twice daily) as prophylaxis against invasive fungal infections in neutropenic patients receiving cytotoxic chemotherapy for AML or MDS (n=602), clinical failure in patients while receiving antifungal prophylaxis and for seven days following the last dose of therapy was lower for posaconazole (27% [82/304]) compared to fluconazole or itraconazole (42% [126/298]), (95% CI for the difference posaconazole-comparator -22.9% to -7.8%). Clinical failure at 100 days post-randomization was 52% (158/304]) for posaconazole compared to 64% (191/298) for fluconazole or itraconazole. All-cause mortality was lower at 100 days for patients receiving posaconazole (14% [44/304]) vs. fluconazole or itraconazole (21% [64/298]). In a randomized, double-blind study that compared posaconazole oral suspension (200 mg three times a day) with fluconazole capsules (400 mg once daily) as prophylaxis against invasive fungal infections in allogeneic HSCT recipients with GVHD (n=600), the clinical failure rate on therapy plus 7 days was 17% (50/301) for posaconazole and 18% (55/299) for fluconazole. Clinical failure through 16 weeks post-randomization was similar for posaconazole (33% [99/301]) and fluconazole (37% [110/299]), (95% CI for the difference posaconazole- -4comparator -11.5% to 3.7%). All-cause mortality was similar at 16 weeks for both treatment arms 19% ([58/301] vs. 20% [59/299]), respectively. In a multicenter, open label study5, the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy was evaluated in patients with invasive aspergillosis who were refractory to or intolerant of conventional antifungal therapy (n=107). Data from external control cases were collected retrospectively to provide a comparative reference group (n=86). , A successful global response at end of treatment was seen in 42% (45/107) of posaconazole-treated patients compared to 26% (22/86) of the external group (P = 0.006). However, this was not a prospective, randomized, controlled study, and so all comparisons with the external control group should be viewed with caution. The most frequently reported adverse reactions across the whole population of healthy volunteers and patients were nausea and headache. POSANOL Delayed-Release Tablets and Oral Suspension are not to be used interchangeably due to the differences in the dosing of each formulation. About Merck Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside Canada and the United States. Through our prescription medicines, vaccines, biologic therapies, and consumer care 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 healthcare through far-reaching policies, programs and partnerships. For more information about our operations in Canada, visit www.merck.ca Forward-Looking Statement This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to -5pipeline 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 forwardlooking 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 healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’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 Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. Merck 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 Merck’s 2013 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). ### References 1. Lin SJ, et al. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001 Feb 1;32(3):358-66. 2. ® POSANOL (posaconazole) Product Monograph. Merck Canada. October 20, 2014. 3. Cornely OA, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25;356(4):348-59. 4. Ullmann AJ, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25;356(4):335-47. 5. Walsh TJ, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007 Jan 1;44(1):2-12.
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