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Chimerix Presents Brincidofovir
(CMX001) Adenovirus Phase 2 Results
Positive Phase 2 Study Results Presented as Late Breaker at ICAAC
DURHAM, N.C., Sept. 11, 2013 (GLOBE NEWSWIRE) -- Chimerix, Inc.
(Nasdaq:CMRX), a biopharmaceutical company developing novel, oral
antivirals in areas of high unmet medical need, today announced the
results from its exploratory Phase 2 Study 202 evaluating brincidofovir
(CMX001) in hematopoietic cell transplant (HCT) recipients with early
adenovirus (AdV) infection. Study 202 was the first trial of an
antiviral agent in AdV infection. Brincidofovir (CMX001) is an
investigational oral nucleotide analog lipid-conjugate that has
demonstrated activity against all pathogenic families of double-stranded
DNA (dsDNA) viruses, including herpesviruses, adenoviruses, and
polyomaviruses.
Michael Grimley, MD, Associate Professor of Clinical Pediatrics in the
Division of Bone Marrow Transplant and Immune Deficiency at Cincinnati
Children's Hospital Medical Center, and the lead investigator in
Chimerix's Phase 2 AdV study, presented the trial results during the
"Viral Infections in Immunosuppressed Hosts" session at the 53rd Annual
Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
meeting on September 10, 2013 in Denver, CO.
"These data strongly support the continued development of CMX001 as a
global prevention for dsDNA viruses, a leading cause of non-relapse
mortality in the months following a transplant," said Dr. Grimley.
Although AdV in HCT recipients has been recognized as a severe and
often-fatal infection in pediatric and adult patients who have undergone
recent HCT, there are no approved antiviral treatments. Potential risk
factors associated with an increased risk of rapid progression to AdV
infection have been identified in the scientific literature, but the
frequency of AdV in the blood or AdV disease was unknown prior to this
trial. Early data from patients who had received CMX001 for AdV
infection through Emergency Investigational New Drug (EIND) regulations
had provided anecdotal evidence of improved outcomes compared with
historic data. This exploratory Phase 2 trial was designed to initiate
CMX001 or placebo during early AdV infection, prior to symptomatic
disease, and to evaluate the potential to decrease AdV viral load or
prevent progression to AdV disease.
Results: Safety and tolerability data from this 48-subject trial
confirmed the lack of hematologic and renal toxicity for once-weekly
(QW) or twice-weekly (BIW) CMX001 dosed for 6-12 weeks, and showed the
successful implementation of the Safety Monitoring and Management Plan
(SMMP) to address gastrointestinal side effects reported in earlier
trials. Temporary dose interruptions for grade 3 diarrhea were
successfully utilized in the trial, with one permanent discontinuation
for diarrhea in the CMX001 QW cohort. Three additional discontinuations
in the trial were reported for abdominal pain (CMX001 BIW cohort), lower
GI hemorrhage (CMX001 BIW cohort), and severe rash (placebo cohort). No
new serious safety issues were identified in this trial, and no changes
were necessary in the safety monitoring in the recently initiated Phase
3 SUPPRESS trial for prevention of CMV.
Efficacy outcomes for Study 202 were progression to possible or probable
AdV disease or significant changes in AdV viremia. Although statistical
significance was not achieved, numerical benefit was demonstrated for
CMX001 100 mg BIW for multiple endpoints:
• Virologic Response: Subjects exposed to CMX001 100 mg BIW demonstrated
a significant rapid decrease in levels of AdV in the blood (viremia)
versus subjects in the CMX001 QW and placebo cohorts. In subjects who
entered the trial with higher levels of AdV viremia (VL > 3.0 log10
copies/mL) viral decline on CMX001 BIW was consistent for seven of eight
(7 of 8, 88%) subjects, all suppressing AdV levels to below the limit of
detection (LOD = 2.0 log10 copies/mL, 100 copies/mL) within the first
week of dosing, versus only one of eight (13%) high-level viremia
subjects in the placebo cohort.
• Treatment Failures: Three of 14 (21%) subjects enrolled in the CMX001
BIW cohort were considered treatment failures with increasing AdV
viremia or progression to AdV disease, versus eight of 16 (50%) subjects
in the CMX001 QW cohort, and six of 18 (33%) subjects in the placebo
cohort.
• Mortality: Overall mortality was lower for the subjects in the CMX001
BIW cohort (2 of 14, 14%) versus the CMX001 QW (5 of 16, 31%) and
placebo (7 of 18, 39%) cohorts.
Adenovirus in the blood was chosen as a potential early indicator of AdV
disease based on the accepted clinical utility of viremia as an early
trigger for initiation of antiviral therapy for CMV in these patients.
Results from this study bring into question whether AdV viremia is an
indicator of early AdV disease. For low-level AdV viremia ( < 3.0 log10
copies/mL), a significant proportion of subjects spontaneously cleared
viremia prior to initiation of therapy or during placebo therapy. These
data indicate that low level AdV viremia may be a transient phenomenon
in some subjects. In contrast, high level AdV viremia ( > 3.0 log10
copies/mL) at screening was often associated with rapid development of
symptoms and end-organ disease even before therapy could be started.
Further research is needed to identify clinical indicators of early AdV
disease which could be used for early intervention, but prevention of
AdV continues to be the preferred strategy through which diseases caused
by dsDNA viruses can be avoided.
"The acceptable safety and tolerability of CMX001, and successful
incorporation of the Safety Monitoring and Management Plan in this
study, were important milestones for the brincidofovir program as we
initiate dosing in the Phase 3 SUPPRESS trial for CMV prevention in HCT
recipients," said M. Michelle Berrey, MD, MPH, Chief Medical Officer of
Chimerix. "Additionally, consistent trends toward decreased progression
of AdV disease and a decrease in overall mortality for subjects
randomized to CMX001 BIW reaffirm our belief that earlier intervention
in viral disease is the preferred strategy to prevent decrease morbidity
and mortality from AdV and other dsDNA viral diseases. Ultimately, we
believe that broad use of CMX001 as a prevention for CMV, AdV, and other
viral diseases that impact immunocompromised patients will prove to be
the best approach."
Summary of CMX001 Study 202 Results Presented at ICAAC
CMX001 BIW initiated at the time of detection of AdV viremia showed
potential clinical benefit in reducing progression to AdV disease and
all-cause mortality. Subset analyses of disease progression and
all-cause mortality were consistent in trends favoring the CMX001 BIW
regimen over placebo or CMX001 QW. A greater proportion of subjects
randomized to CMX001 BIW achieved undetectable levels of AdV viremia
during randomized therapy and a lower proportion of subjects on the BIW
regimen progressed to symptomatic disease compared to placebo or CMX001
QW.
CMX001 Study 202 Design
Study 202 was a randomized, blinded, placebo-controlled proof-of-concept
trial assessing the use of CMX001 as a preemptive therapy for AdV
infection. HCT recipients were randomized into the study upon appearance
of detectable AdV viremia but before the appearance of symptoms of AdV
disease. Subjects were randomized to one of three dosing regimens:
CMX001 BIW, CMX001 QW or placebo. Forty-eight pediatric and adult
subjects were randomized into the trial beginning in June 2011.
The design of the study was based on the limited information available
on the natural history of AdV infection in immunocompromised subjects,
preliminary and uncontrolled data available on the activity of CMX001
against AdV, ethical considerations due to the placebo-controlled design
and high mortality associated with AdV disease in HCT recipients and
epidemiologic data indicating a low incidence of AdV viremia in subjects
post-HCT.
About Brincidofovir (CMX001)
Brincidofovir is an investigational oral nucleotide analog
lipid-conjugate that has shown broad-spectrum antiviral activity against
all five families of dsDNA viruses that affect humans, including
herpesviruses such as CMV, adenoviruses, polyomaviruses such as BKV,
papillomaviruses, and orthopoxviruses. Brincidofovir has a favorable
safety and tolerability profile, with no evidence of kidney or bone
marrow toxicity in over 900 patients dosed with brincidofovir for
prevention, preemptive therapy, or treatment of dsDNA viruses that cause
disease in humans.
In a Phase 2 trial of 230 HCT recipients, brincidofovir demonstrated
potential clinical utility in prevention of CMV infection. In this same
CMV trial, brincidofovir-treated subjects had improvements in kidney
function and hematuria (blood in the urine) when compared to
placebo-treated subjects, suggesting that brincidofovir may reduce
BKV-associated bladder and renal damage.
On September 9, 2013, Chimerix announced the initiation of its Phase 3
SUPPRESS trial evaluating 100mg CMX001 BIW for the prevention of CMV in
HCT recipients.
About Hematopoietic Cell Transplantation (HCT)
HCT is a medical procedure performed most frequently for hematology and
oncology indications 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. Because of chemotherapy and
immunosuppressants that are used before, during and after the procedure,
patients are highly susceptible to viral, bacterial and fungal
infections and associated complications related to the chemotherapy and
immunosuppression. These post-transplant complications are a significant
cause of morbidities and mortalities following the procedure.
About Chimerix
Chimerix, a biopharmaceutical company based in Durham, NC, 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. Brincidofovir has shown broad-spectrum activity against
dsDNA viruses, including herpesviruses, adenoviruses and polyomaviruses.
On September 9, 2013, Chimerix announced the initiation of its Phase 3
SUPPRESS trial evaluating 100mg CMX001 BIW for the prevention of CMV in
HCT recipients. 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 Chimerix's Phase 3 SUPPRESS trial, the efficacy
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 SUPPRESS; the
demonstrated efficacy of brincidofovir in the SUPPRESS trial; and
regulatory developments in the United States and foreign countries.
Other risks and uncertainties affecting Chimerix 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, its most recently filed reports on Form 8-K and other documents
subsequently filed with or furnished to 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 |