AiCuris and Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced the publication of results from a Phase 2
clinical trial evaluating the safety and efficacy of letermovir, an
investigational, oral antiviral agent for the prevention of human
cytomegalovirus (CMV) infection in patients receiving bone marrow
transplant. The results published in the latest issue of the New
England Journal of Medicine (NEJM) show that
letermovir in CMV-seropositive allogeneic human blood precursor cell
recipients (bone marrow transplant patients) met the study’s two primary
efficacy endpoints. Merck plans to conduct a Phase 3 trial of
letermovir, also known as AIC246 or MK-8228, starting in the first half
of 2014.
“We are very pleased to see the encouraging data regarding the efficacy
and tolerability of our innovative drug for treatment of CMV infection
among transplant recipients published in this prestigious journal,”
notes Prof. Helga Rübsamen-Schaeff, CEO of AiCuris. “We are looking
forward to the start of Phase 3 clinical testing.”
The paper describes the findings of a Phase 2 double-blind, randomized,
placebo-controlled trial, evaluating the effect of letermovir on the
incidence and time-to-onset of CMV prophylaxis failure in CMV
seropositive matched bone marrow transplant recipients during 12 weeks
of treatment. Patients (n=131) received one of three oral doses of
letermovir (60, 120, 240 mg/day) or placebo starting after engraftment.
The primary endpoint was all-cause prophylaxis failure defined as
discontinuation of study drug due to CMV antigen or CMV DNA detection,
end-organ disease, or any other causes unrelated to CMV. The primary
efficacy analysis population was a modified intention-to-treat (mITT),
which included all patients who received at least one dose of the study
drug and had at least one measurement of the CMV viral load during the
study.
“Based on the data from this study, and Merck’s own evaluations, we are
pleased to be moving forward with plans to initiate a Phase 3 trial of
letermovir in the first half of this year,” said Dr. Eliav Barr, vice
president, Infectious Diseases, Merck Research Laboratories.
In the Phase 2 study (sponsored by AiCuris), the incidence of all-cause
prophylaxis failure in the mITT population was significantly lower in
the groups that received letermovir at doses of 120 mg/day or 240
mg/day, compared with the placebo group (32% and 29% vs. 64%; p = 0.01
and p = 0.007, respectively). The incidence of virololgic failure was
also markedly lower in the 240 mg group (6%) than in the 120 mg group
(19%), the 60-mg group (21%), or the placebo group (36%). Virologic
failure was defined as either detectable CMV antigen or DNA in blood at
two consecutive time points (with at least one instance confirmed by the
central laboratory), leading to discontinuation of the study drug and
administration of rescue medication, or the development of CMV end-organ
disease. No virologic failures were observed in patients receiving the
240 mg dose of letermovir who were CMV negative at baseline.
The other primary end point, the time to the onset of prophylaxis
failure, was significantly shorter in the 240 mg group (range, 1 to 8
days) than in the placebo group (range, 1 to 21 days) (P-0.002), but
comparisons with the placebo group were not significant for the 60-mg
group (range, 1 to 42 days; P=0.15) or the 120-mg group (range, 1 to 15
days; P=0.13). A separation of the Kaplan-Meier curves was evident
between the 240 mg group and the placebo group after 8 days. The median
time to prophylaxis failure could not be calculated because of the low
incidence. These results were consistent with those in the per-protocol
population.
The most common recorded adverse events during treatment were
gastrointestinal disorders (diarrhea, nausea, and vomiting) in 66
percent of patients in the letermovir groups versus 61 percent in the
placebo group. The majority of these events were of mild or moderate
intensity; 24 percent of letermovir treated patients versus 30 percent
of placebo patients experienced severe adverse events during treatment.
Under an agreement signed in 2012, Merck (through a subsidiary)
purchased worldwide rights to develop and commercialize letermovir from
AiCuris.
About Letermovir
Letermovir is an investigational oral, once-daily candidate for the
prevention and treatment of HCMV infection. It is derived from a novel
chemical class (quinazolines) and is designed to inhibit the HCMV viral
terminase. Letermovir has been granted Orphan Product Designation by the
EMA and FDA for the prevention of CMV viremia and disease in at-risk
populations, and has also been granted Fast Track Status in the United
States.
About HCMV
The Human Cytomegalovirus (HCMV) is widely spread in the human
population and can cause severe, life-threatening infections in cases of
immune incompetency or immune deficiency, such as, for example, cases in
transplant recipients, newborn babies and HIV/AIDS patients. HCMV
infection is characterized by fever, leucopenia (very low white blood
cell count) and thrombocytopenia (very low platelet numbers) with or
without specific organ dysfunction. Two main strategies to prevent HCMV
infection have been adopted: anti-HCMV drug prophylaxis or pre-emptive
treatment of transplant recipients who are at risk and have evidence of
HCMV infection upon screening.
About AiCuris
AiCuris GmbH & Co KG (name derived from Anti-Infective Cures) was
founded in 2006 and is focused exclusively on the discovery, research
and development of novel, resistance breaking antiviral and
antibacterial agents for the treatment of severe and potentially
life-threatening infectious diseases. Majority investors are Drs.
Strüngmann, founders and former owners of the pharmaceutical company
Hexal. Besides the HCMV program, AiCuris is pursuing several other
candidates in various stages of clinical development including a
Gram-negative, resistance-breaking antibiotic for hospital use, an
immune modulator for Hepatitis B and fibrosis, an HIV compound and
several research projects in Hepatitis B and bacteriology. A novel
antiHerpes Simplex compound completed phase II clinical testing. For
more information, please visit www.aicuris.com.
About Merck
Today's Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside the United States and Canada.
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, visit www.merck.com
and connect with us on Twitter,
Facebook
and YouTube.
Merck 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 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; 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).
Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20140508005910/en/
Copyright Business Wire 2014