– Results Show Early Virologic Response
Associated with Better Overall Survival –
Chimerix (NASDAQ:CMRX), a biopharmaceutical company developing
novel antivirals in areas of high unmet medical need, today
announced the presentation of detailed 24-week interim results from
the AdVise trial of brincidofovir for the treatment of adenovirus
(AdV) infection in allogeneic hematopoietic cell transplant (HCT)
recipients at the annual Infectious Diseases conference,
IDWeek
™ held October 26-30, 2016 in New
Orleans,
LA.
The results will be presented by Dr. Michael Grimley, Associate
Professor, Division of Bone Marrow Transplant and Immune
Deficiency, Cincinnati Children's Hospital, on Saturday, October
29.
“This presentation builds upon the top-line 24-week AdVise results
that we announced earlier this year. HCT recipients who were
treated with brincidofovir experienced a rapid decline in
adenovirus viral load, and overall survival was higher in subjects
who had a rapid antiviral response compared with those who did
not,” said Garrett Nichols, MD, MS, Chief Medical Officer
at Chimerix. “Importantly, these data continue to advance our
scientific understanding of adenovirus infection, including key
risk factors for rapid progression of disease within this complex
population; these advances will help us predict which patients are
most likely to benefit from brincidofovir as we work to design our
next studies.”
The AdVise trial was an open-label, multicenter study designed
to evaluate the efficacy, safety and overall tolerability of
brincidofovir for the treatment of AdV infection. In study 304,
pediatric and adult patients were placed into one of three cohorts:
Cohort A, comprised of allogeneic HCT recipients with asymptomatic
or limited AdV infection; Cohort B, comprised of allogeneic HCT
recipients with disseminated AdV disease; and Cohort C, comprised
of autologous HCT recipients, solid organ transplant recipients and
other immunocompromised patients. All subjects were to receive 12
weeks of oral brincidofovir and were followed for 24 weeks after
completing treatment. This interim analysis examines outcomes at 24
weeks after the first brincidofovir dose (12 weeks after prescribed
dosing duration) and includes 158 patients assigned to Cohorts A
(23 adult and 43 pediatric patients) and B (35 adult and 57
pediatric patients).
The primary efficacy endpoint of the AdVise trial was all-cause
mortality at Day 60 after the first brincidofovir dose in allo-HCT
recipients with disseminated AdV disease, a group in which 50-80
percent mortality has been reported in the literature. All-cause
mortality in Cohort B at Day 60 was 19 percent in pediatric
subjects and 43 percent in adults.
Importantly, new data from an interim analysis at 24 weeks,
presented at IDWeek™, showed marked declines in AdV viremia that
were observed in both cohorts. Undetectable viremia at the end of
treatment was achieved in 61 percent of patients in Cohort A, and
in 49 percent of patients in Cohort B. Additionally, a robust
antiviral response was observed despite very low baseline
lymphocyte counts and CD4+ cell counts in this population. In
patients with poor immune function, defined as baseline CD4+ cell
counts below 50 cells/μL, 55 percent in Cohort A and 52 percent in
Cohort B had a rapid virologic response (≥2 log10 copies/mL decline
or undetectable levels of AdV at Week 4).
Post-Hoc Analyses Show Impact of Early Detection and
Treatment
Post-hoc analyses were conducted to investigate the correlation
between rapid virologic response to brincidofovir treatment and
time to subsequent mortality.
- The analyses compared patients who achieved a ≥2-log10
copies/mL decline or undetectable AdV viremia at Week 4, or
undetectable AdV viremia at Week 6 (responders), with patients who
did not achieve these thresholds (non-responders).
- In patients with disseminated AdV disease who were alive at
Week 4, 84 percent of pediatric patients and 50 percent of adult
patients achieved a ≥2 log decline or undetectable AdV viremia by
that time. This rapid virologic response was associated with
improved survival at Week 24 in both pediatric and adult patients
(75 percent of pediatric and 54 percent of adult responders
survived to Week 24, compared with 29 percent and 15 percent of
non-responders, respectively). All p-values <0.05.
- In patients with disseminated AdV disease who were alive at
Week 6, 68 percent of pediatric patients and 42 percent of adult
patients achieved undetectable AdV viremia by that time. This
response was associated with improved survival at Week 24 in both
pediatric and adult patients (82 percent of pediatric and 70
percent of adult responders survived to Week 24, compared with 46
percent and 14 percent of non-responders, respectively).
- The first patient(s) at each participating site may have
experienced delays between diagnosis and treatment with
brincidofovir because of the time required to secure institutional
review board approval, as one possible reason. Assessment of
enrollment period as a covariate demonstrated a period effect with
lower mortality in Cohort B pediatric patients enrolled in the last
quartile (14 percent mortality at Week 24) compared to those
enrolled at the beginning of the study (60 percent mortality at
Week 24), reflecting the importance of rapid diagnosis and
treatment before multiple organ failure; differences were less
pronounced in adults.
- The most commonly reported treatment-emergent adverse events
were gastrointestinal (GI) symptoms, increases in serum
transaminases and bilirubin, and acute graft-versus-host disease
(GvHD). No events were reported that were suggestive of
drug-related nephrotoxicity or myelosuppression.
Additional Observations on Survival and Viremia
Data
- All-cause mortality at 24 Weeks was lower in pediatric patients
than adult patients in both cohorts. Pediatric all-cause mortality
was 33 percent in Cohort A and 42 percent in Cohort B. Adult
all-cause mortality was 48 percent in Cohort A and 71 percent in
Cohort B.
- AdV-related mortality at Week 24 in pediatric patients was 9
percent in Cohort A and 14 percent in Cohort B. AdV-related
mortality at Week 24 in adult patients was 4 percent in Cohort A
and 46 percent in Cohort B.
- Any prior treatment with cidofovir in Cohort B appeared to have
little impact on overall mortality (30 percent in patients with
prior cidofovir use at Day 60, compared to 27 percent in patients
with no prior use of cidofovir).
Brincidofovir was discontinued due to adverse events (AEs) in 20
percent of pediatric patients and 29 percent of adult patients,
with GI events cited as the most common reason (5 percent and 14
percent respectively).
The most commonly reported fatal AEs in Cohort B were
multi-organ failure (18 percent pediatric, 14 percent adults),
acute GvHD (4 percent pediatric, 20 percent adults), AdV infection
(4 percent pediatric, 14 percent adults), and respiratory failure
(7 percent pediatric, 9 percent adults).
As previously communicated, in study 305 an attempt was made to
compare survival outcomes with matched historical controls, but the
baseline risk factors for the control patients (including several
recognized co-morbidities) did not match the high-risk patients in
AdVise and a meaningful difference in overall survival between the
AdVise patients and historical controls was not observed.
The company plans to present full 36-week data from the AdVise
study during the first quarter of 2017.
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 not been associated with kidney or bone marrow toxicity in over
1,000 patients treated to date. Brincidofovir has received Fast
Track designation from the FDA for adenovirus,
cytomegalovirus (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 (COMP) 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 novel antivirals in
areas of high unmet medical need. Chimerix's proprietary lipid
conjugate technology has produced brincidofovir (BCV, CMX001);
CMX157, which was licensed to ContraVir Pharmaceuticals in 2014;
and earlier-stage clinical candidates. 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 brincidofovir, that FDA and other
regulatory authorities may not approve brincidofovir or
brincidofovir-based regimens, and that marketing approvals, if
granted, may have significant limitations on their use. As a
result, brincidofovir may never be successfully commercialized. In
addition, Chimerix may be unable to file for regulatory
approval for brincidofovir 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.
CONTACT:
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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