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Chimerix Announces Publication of
Positive Phase 2 Results of Brincidofovir (CMX001) in the New England
Journal of Medicine
Phase 2 Trial Evaluated Brincidofovir for the Prevention of
Cytomegalovirus (CMV) Infection in Hematopoietic Cell Transplant
Recipients
DURHAM, N.C., Sept. 26, 2013 (GLOBE NEWSWIRE) -- Chimerix, Inc.
(Nasdaq:CMRX), a biopharmaceutical company developing novel, oral
antivirals in areas of high unmet medical need, today announced the
publication of results from its Phase 2 Study CMX001-201 evaluating
brincidofovir (CMX001) for the prevention of cytomegalovirus (CMV)
infection in hematopoietic cell transplant (HCT) recipients. The
article, entitled "CMX001 to Prevent Cytomegalovirus Disease in
Hematopoietic-Cell Transplantation," appears in the September 26th issue
of the New England Journal of Medicine (N Engl J Med 369:1227-36).
Brincidofovir, Chimerix's lead product candidate, is an investigational
oral nucleotide analog lipid-conjugate that has shown broad-spectrum
antiviral activity against double-stranded DNA (dsDNA) viruses including
CMV. Study CMX001-201, a 230-subject, randomized, placebo-controlled,
double-blind, dose-escalation study, met the primary endpoint of
reduction in CMV viremia and/or CMV disease for brincidofovir 100 mg
twice weekly versus placebo (p=0.002). Based on these positive Phase 2
results, Chimerix recently initiated the Phase 3 SUPPRESS trial of
brincidofovir 100 mg twice weekly for the prevention of CMV infection in
HCT recipients.
"Although prevention of CMV infection has been recognized as a superior
approach to decrease CMV-related morbidity and mortality in the months
following hematopoietic cell transplantation, the side effects of
available antivirals have precluded their approval and use in this
setting," said M. Michelle Berrey, MD, MPH, Chief Medical Officer of
Chimerix. "The significant decrease in CMV events and lack of
hematologic and renal toxicity shown in Study CMX001-201 provided the
supportive data to allow us to progress brincidofovir into the Phase 3
SUPPRESS trial."
CMX001-201 Study Results
The primary endpoint for Study CMX001-201 was the incidence of CMV
disease at any time during therapy or a CMV polymerase chain reaction
(PCR) assay result of greater than 200 copies/mL (the lower limit of
quantification of the assay) at the time of the last dose of study drug.
All brincidofovir doses and dose regimens demonstrated antiviral
activity when compared to placebo, with the exception of the lowest
dose, 40 mg once weekly. The proportion of subjects who developed CMV
disease or a CMV PCR positive result at the end of the 100 mg twice
weekly dosing period was 10% (five of 50) versus 37% (22 of 59) in the
placebo-treated group (p=0.002).
In a pre-specified subgroup of subjects who were CMV PCR negative at
baseline (the subject population being enrolled in SUPPRESS), zero of 41
subjects in the brincidofovir 100 mg twice weekly group developed CMV
PCR of ≥ 1,000 copies/mL during the dosing period, compared to 15 of 47
subjects (32%) in the placebo group (p < 0.001). The twice weekly dosing
regimen was more effective than the same total dose given once weekly,
leading to the selection of the 100 mg twice weekly dosing regimen for
further development in SUPPRESS.
In subjects who received brincidofovir, there was no evidence of kidney
or bone marrow toxicity, both associated with available anti-CMV
therapies. Diarrhea was the most frequent adverse event in the Phase 2
study and was addressed with a safety management algorithm in the final
cohort, which reduced the number of discontinuations due to diarrhea and
allowed a majority of subjects to complete the intended course of
therapy. The safety management algorithm has been incorporated in
subsequent brincidofovir studies including the ongoing SUPPRESS trial.
CMX001-201 Study Design
Study CMX001-201 was a randomized, double-blind, placebo-controlled,
dose-escalation multi-center Phase 2 trial evaluating the safety,
tolerability and efficacy of CMX001 to prevent or control CMV disease in
230 allogeneic HCT recipients at high risk of CMV infection. Following
engraftment, or evidence of successful production of new blood cells by
the new bone marrow, subjects were randomized into five sequential,
dose-escalating cohorts to receive either brincidofovir or placebo, at
doses ranging from 40 mg once weekly to 200 mg twice weekly. Subjects
were treated for nine to 11 weeks through post-transplant Week 13, after
which subjects were followed for an additional four to eight weeks.
About Brincidofovir (CMX001)
Chimerix's lead product candidate, brincidofovir (CMX001), is an oral
nucleotide analog that has shown broad-spectrum antiviral activity
against all five families of dsDNA viruses that affect humans, including
cytomegalovirus (CMV), adenovirus (AdV), BK virus and herpes simplex
viruses. Chimerix initiated the Phase 3 SUPPRESS trial of brincidofovir
for the prevention of CMV infection in the third quarter of 2013.
SUPPRESS will support Chimerix's initial regulatory submission for
prevention of CMV infection in adult HCT recipients. At the Annual ICAAC
Conference in September 2013, Chimerix presented positive data from its
Phase 2 trial evaluating brincidofovir as a preemptive therapy for AdV,
an often-fatal infection with no approved treatment.
About the Phase 3 SUPPRESS Trial
The Phase 3 SUPPRESS trial of brincidofovir (CMX001) is designed to
demonstrate the efficacy and safety of brincidofovir for the prevention
of CMV infection versus a placebo control, as no therapy is currently
approved for the prevention of CMV in HCT recipients. The primary
endpoint for SUPPRESS is prevention of clinically significant CMV
infection through the first 24 weeks post-transplant. The trial is
powered to detect a relative 50% decrease in clinically significant CMV
infection in subjects receiving brincidofovir versus those receiving
placebo. Secondary endpoints in the SUPPRESS trial include clinical
events and other evidence of dsDNA viral infections, including
adenovirus (AdV), varicellovirus (VZV), BK virus (BKV), and other
herpesviruses such as HHV-6, which contribute to morbidity and mortality
in the first year following HCT.
SUPPRESS is anticipated to enroll approximately 450 HCT recipients who
are at increased risk of CMV infection, with approximately 300 of the
450 enrolled subjects receiving 100 mg twice weekly (BIW) brincidofovir
versus placebo (2-to-1 ratio). Dosing of study drug will begin shortly
after subjects receive their transplant, and will not require evidence
of stem cell "engraftment" (evidence of production of blood cells by the
new transplant), a safety precaution in the Phase 2 trial of
brincidofovir and other recent trials of investigational antivirals for
CMV prevention. The ability to begin prevention during the early
post-transplant period may decrease the risk of CMV infection in
transplant patients.
Subjects enrolled in SUPPRESS will receive brincidofovir or placebo from
the early post-transplant period through Week 14 post-transplant, the
period of highest risk for viral reactivation. Enrolled subjects will
continue to be monitored for evidence of CMV reactivation and other
dsDNA viral infections through Week 24 post-transplant. Approximately 40
transplant centers will participate in SUPPRESS.
Data from SUPPRESS are anticipated in 2015 and, if positive, may support
Accelerated Approval of brincidofovir for the prevention of CMV
infection.
About Hematopoietic Cell Transplantation (HCT)
HCT (also known as bone marrow transplantation) is a medical procedure
performed to treat patients with certain cancers of the blood and bone
marrow, such as multiple myeloma or leukemia, or genetic diseases. For
these patients, replacement of the blood forming system is the best
therapeutic alternative. Chemotherapy and radiation used to kill any
cancer cells before the transplant can leave patients susceptible to
viral, bacterial and fungal infections and associated complications, a
significant cause of morbidities and mortalities following HCT.
About Chimerix
Chimerix is committed to the discovery, development and
commercialization of novel, oral antiviral therapeutics designed to
transform patient care in areas of high unmet medical need. Chimerix's
proprietary lipid technology has given rise to two clinical-stage
nucleotide analog lipid-conjugates, brincidofovir (CMX001) and CMX157,
which have demonstrated the potential for enhanced activity and safety
in convenient, orally administered dosing regimens. Chimerix's second
product candidate, CMX157, an oral nucleotide analog for the treatment
of HIV infection, was licensed to Merck in July 2012.
Forward-Looking Statements
Statements contained in this press release regarding matters that are
not historical facts are "forward-looking statements" within the meaning
of the Private Securities Litigation Reform Act of 1995. Because such
statements are subject to risks and uncertainties, actual results may
differ materially from those expressed or implied by such
forward-looking statements. Such statements include, but are not limited
to, statements regarding the clinical development and use of
brincidofovir and its ability to provide a broad spectrum of antiviral
activity and the positive impact of brincidofovir on transplant
recipients. Risks that contribute to the uncertain nature of the
forward-looking statements include: the success of the SUPPRESS trial;
the demonstrated efficacy of brincidofovir in the SUPPRESS trial; the
accuracy of Chimerix's estimates regarding expenses and capital
requirements; regulatory developments in the United States and foreign
countries; Chimerix's ability to obtain and maintain intellectual
property protection for brincidofovir; and the loss of key scientific or
management personnel. These and other risks and uncertainties are
described more fully in Chimerix's filings with the Securities and
Exchange Commission, including without limitation its most recent
Quarterly Report on Form 10-Q, as filed with the Securities and Exchange
Commission. All forward-looking statements contained in this press
release speak only as of the date on which they were made. Chimerix
undertakes no obligation to update such statements to reflect events
that occur or circumstances that exist after the date on which they were
made.
Contact
Chimerix Contact:
Joseph T. Schepers
Executive Director,
Investor Relations and Corporate Communications
jschepers @chimerix.com
919-287-4125
Media Contact:
Tony Plohoros
tplohoros @6degreespr.com
908-940-0135
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