-- Results show higher survival rate in
adenovirus-infected patients with a virologic response to
brincidofovir -- -- Mortality rates were lower in pediatric
patients than in adult patients --
Chimerix (NASDAQ:CMRX) today announced the presentation of final
data from the AdVise trial of brincidofovir for the treatment of
adenovirus (AdV) infection in allogeneic hematopoietic cell
transplant (HCT) recipients at the BMT Tandem Meetings held
February 22-26, 2017 in Orlando, FL.
“The final data highlight the clinical benefit of
the early antiviral effect of brincidofovir on adenovirus,” said
Dr. Vinod K. Prasad, Professor of Pediatrics, Duke University
School of Medicine, and an investigator in the AdVise trial. “Rapid
declines in adenovirus viral load were observed over the first four
weeks of treatment, even in patients whose immune systems had not
yet recovered. Importantly, patients who had a virologic response
to brincidofovir showed higher survival, as did those who were
treated earlier in the disease course. Adenovirus infection is a
serious problem in HCT patients and this study showed encouraging
results, particularly in children.”
The AdVise trial was an open-label, multicenter
study designed to evaluate the efficacy, safety and overall
tolerability of oral brincidofovir for the treatment of adenovirus
infection. Pediatric and adult subjects were assigned to one of
three cohorts:
- Cohort A, comprised of allogeneic HCT recipients with
asymptomatic or limited adenovirus infection;
- Cohort B, comprised of allogeneic HCT recipients with
disseminated adenovirus disease; and
- Cohort C, comprised of autologous HCT recipients, solid organ
transplant recipients and other patients with serious adenovirus
infections.
All subjects were to receive 12 weeks of oral
brincidofovir and were followed for at least 36 weeks. This final
analysis includes 158 allogeneic HCT recipients assigned to Cohorts
A (23 adult and 42 pediatric patients) and B (35 adult and 58
pediatric patients).
In the AdVise trial, declines in AdV viral load of
≥2 log10 c/mL or below the limit of detection at Week 4 were
observed in 76 percent of pediatric patients and 45 percent of
adult patients. Notably, this antiviral effect was observed
even in HCT recipients who did not yet have immune recovery. In
Cohort A, 55 percent of patients with baseline low immunity (CD4
counts <50 cells/μL) achieved ≥2 log10 c/mL decline or
undetectable AdV at Week 4. In Cohort B, 52 percent of patients
with baseline low immunity achieved ≥2 log10 c/mL decline or
undetectable AdV over the same period of time.
In patients with disseminated disease, rapid
virologic response, defined as undetectable AdV viremia at Week 6,
was associated with nearly double the survival rate and lower
adenovirus-associated mortality compared with subjects who did not
have an antiviral response.
|
|
Mortality |
AdV-Associated Mortality |
Pediatric |
Responder* |
7/28
(25%) |
p=0.031 |
1/28 (4%) |
Non-responder |
7/13 (54%) |
2/13 (15%) |
Adult |
Responder* |
5/10
(50%) |
p=0.0004 |
0/10 (0%) |
Non-responder |
13/14 (93%) |
10/14 (71%) |
*Responders defined as subjects with baseline AdV
viremia still on study at Week 6 who had undetectable plasma AdV at
Week 6; non-responders defined as subjects who did not achieve the
specified cut-off. A Cox model incorporating age group was used to
compare mortality at 36 weeks in responders and
non-responders.
Diarrhea was the most commonly reported treatment
emergent adverse event in the AdVise trial, reported in 38 percent
of adult and 43 percent of pediatric HCT recipients. Many subjects
enrolled in the AdVise trial, particularly in the first few months
of the study, were begun on therapy at a point when they had
multiple organ failure or other diagnoses likely to negatively
impact their ability to survive the first four weeks of treatment.
There was therefore a significant improvement in survival observed
for subjects enrolled in the fourth quartile who were begun on
brincidofovir with lower viral loads and a shorter time from AdV
diagnosis to initiation of treatment. In the anticipated Study 999,
patients who are unlikely to survive four weeks will not be
enrolled in the trial.
“AdVise is the first interventional trial in
patients with serious adenovirus infections, a highly fatal disease
after transplant. Because the median time to clear adenovirus from
plasma in pediatric subjects was only 2-3 weeks, shorter courses of
therapy with brincidofovir may deliver antiviral benefit and
improve overall outcomes while limiting the risk of GI toxicity,”
said Garrett Nichols, MD, MS, and Chief Medical Officer
at Chimerix. “We plan to conduct a small comparative study in
about 100 patients with short course oral brincidofovir to optimize
outcomes in serious adenovirus disease.”
About Adenovirus
Adenovirus (AdV) causes gastrointestinal and upper
respiratory infections, including the common cold, in individuals
with a functional immune system. However, in people with a weakened
immune system, adenovirus can lead to life-threatening infections,
including pneumonia and hepatitis. Pediatric and adult patients who
have undergone allogeneic hematopoietic cell transplants (HCT) are
at especially high risk for serious or fatal AdV infections due to
profound immunodeficiency. Mortality rates of 50 to 80 percent have
been reported in the literature for disseminated AdV disease. Rates
of AdV infection with virus detected in the blood or other body
fluids are higher in pediatric transplant recipients than in
adults, and have resulted in many medical centers instituting
screening protocols to detect AdV infection before the virus causes
serious disease. There is currently no approved therapy for AdV
infection, and although progression to disseminated disease in
pediatric HCT recipients occurs in a small proportion of patients
with AdV viremia, mortality rates for pediatric patients with
confirmed AdV disease is greater than 50 percent in the first three
months after diagnosis.
About Brincidofovir
Chimerix's lead product candidate,
brincidofovir, is a nucleotide analog that has shown in
vitro antiviral activity against all five families of DNA
viruses that affect humans, including the herpesviruses and
adenoviruses. Brincidofovir has a high barrier to resistance, no
myelosuppression and low risk of nephrotoxicity. Brincidofovir has
received Fast Track designation from the FDA for
adenovirus, CMV and smallpox. Brincidofovir has also received
Orphan Medicinal Product Designation from the European Commission
for the treatment of adenovirus and for the prevention of CMV
disease, and the Committee for Orphan Medicinal Products has issued
a positive opinion for an Orphan Designation for the treatment of
smallpox.
About Chimerix
Chimerix is a biopharmaceutical company dedicated
to discovering, developing and commercializing medicines that
improve outcomes for immunocompromised patients. Chimerix's
proprietary lipid conjugate technology has produced brincidofovir
(BCV); CMX157, which was licensed to ContraVir Pharmaceuticals; and
earlier-stage clinical candidates. Chimerix recently announced
a new clinical candidate, CMX521, for the treatment and/or
prevention of norovirus. For further information, please visit
Chimerix's website, www.chimerix.com.
Forward-Looking Statements
This press release includes forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995 that are subject to risks, uncertainties and
other factors, including the possibility that there may not be a
viable continued development path for BCV, that any clinical trials
we may conduct will not demonstrate adequate efficacy and safety of
BCV, that enrollment in clinical trials we may conduct may be
insufficient or slower than we anticipate, that the FDA and
other regulatory authorities may not approve BCV or BCV-based
regimens, and that marketing approvals, if granted, may have
significant limitations on their use. As a result, BCV may never be
successfully commercialized. In addition, Chimerix may be
unable to file for regulatory approval for BCV with other
regulatory authorities. These risks, uncertainties and other
factors could cause actual results to differ materially from those
expressed or implied by such forward-looking statements. Risks are
described more fully in the Company's filings with the Securities
and Exchange Commission, including without limitation the Company's
most recent Quarterly Report on Form 10-Q and other documents
subsequently filed with or furnished to the Securities and Exchange
Commission. All forward-looking statements contained in this
Current Report on Form 8-K speak only as of the date on which they
were made. The Company undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
Investor Relations:
ir@chimerix.com
or
Will O’Connor
Stern Investor Relations
Will@sternir.com
212-362-1200
Media:
Becky Vonsiatsky
W2O Group
bvonsiatsky@w2ogroup.com
413-478-2003
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