EXTON, Pa., June 27, 2013 /PRNewswire/ -- ViroPharma
Incorporated (Nasdaq: VPHM) today announced updated data from the
two ongoing, Phase 2 dose ranging studies investigating maribavir
for both first line treatment of cytomegalovirus (CMV) viremia and
treatment of resistant/refractory CMV.
ViroPharma is currently conducting two Phase 2 dose ranging
studies of oral maribavir at one of three doses (400mg, 800mg or
1200mg BID) in transplant recipients. The first is a randomized,
active (valganciclovir) controlled maribavir dose blinded
multicenter Phase 2 study in up to 160 European hematopoietic stem
cell or solid organ transplant recipients who have demonstrated CMV
viremia but do not have CMV organ disease. ViroPharma is also
conducting a randomized, dose blinded multicenter Phase 2
study intended to enroll up to 120 hematopoietic stem cell or solid
organ transplant recipients who have resistant or refractory CMV
viremia with or without CMV organ disease. In both studies
investigators have flexibility in determining duration of treatment
depending on a subject's response. The resistant/refractory study
has been conducted in the U.S. to date and is now being expanded to
add additional EU sites.
Between the two studies, preliminary virology data are available
from 83 subjects who have been followed for at least three weeks
(52 in the "asymptomatic" CMV viremia treatment study and 31 in the
U.S. resistant/refractory CMV treatment study).
In the asymptomatic CMV viremia study, among 39 subjects
receiving maribavir (all doses combined), 36 (92 percent) achieved
plasma CMV DNA levels below the quantification limit (BQL) during
therapy, 1 subject failed to achieve BQL while on therapy, and 2
subjects had withdrawn for non-virologic reasons prior to achieving
BQL. Two of the 36 subjects who achieved BQL subsequently
experienced virologic breakthrough (detectable plasma CMV DNA at
any level, even if levels returned to BQL at later visits) while on
treatment. Among 13 subjects receiving valganciclovir, 9 (69
percent) achieved BQL during therapy, 1 subject failed to achieve
BQL while on therapy, and 3 subjects had withdrawn for
non-virologic reasons prior to achieving BQL. One of the 9
subjects receiving valganciclovir who achieved BQL subsequently
experienced virologic breakthrough while on treatment.
In the study of resistant/refractory CMV, among 31 subjects
receiving maribavir, 26 (84 percent) achieved BQL during therapy, 4
subjects failed to achieve BQL while on therapy, and 1 subject had
withdrawn for non-virologic reasons prior to achieving BQL.
Eleven of the 26 subjects who achieved BQL subsequently experienced
virologic breakthrough while on treatment.
As a reminder, these studies are ongoing, so different subjects
have been followed for different periods of time. Also all
subjects will continue to be followed after the end of treatment to
monitor for the return of detectable plasma CMV DNA when off
antiviral therapy (which is not uncommon following the use of
currently available anti-CMV therapies).
To date, in both ongoing studies maribavir appears to
demonstrate a favorable safety and tolerability profile. An
independent data monitoring committee is monitoring the studies,
and to date it has convened once to review data from the
asymptomatic study with no findings of concern. Adverse
events seen in these studies appear generally consistent with those
expected in transplant recipient populations and what has been
observed in more than 1,000 patients who have received maribavir in
previous clinical studies.
"The results we've seen to date are very positive and
encouraging," stated Vincent Milano,
ViroPharma's president and chief executive officer. "We
appear to have very good response – about 90 percent - in treating
asymptomatic CMV viremia, which is what one would expect for a
potent anti-CMV treatment. Not surprisingly, the
resistant/refractory patients are more complicated, and we are
seeing nearly 85 percent of patients attaining undetectable viral
levels and a sustained antiviral response through the end of
treatment in roughly half of the enrolled subjects, which is
impressive given the lack of treatment options and high unmet need
in these patients. There remain a number of elements of the
studies which we will not be able to fully analyze until after
study completion (including effects of maribavir dose,
pre-treatment viral load, emergence of viral resistance and various
patient factors). These data are consistent with what we had hoped
to see and had seen in previous clinical experiences with maribavir
as a treatment for CMV. We are now fully committed to this
development program and intend to focus on accelerating the
completion of both studies. As a result, moving forward, we
intend to limit the number of future interim data disclosures."
About Maribavir
Maribavir, a member of a new class of drugs called benzimidazole
ribosides, is a potent and selective, orally bioavailable antiviral
drug with a unique mechanism of action against cytomegalovirus and
a favorable clinical safety profile. Unlike currently available
anti-CMV agents that inhibit CMV DNA polymerase, maribavir inhibits
viral DNA assembly and inhibits egress of viral capsids from the
nucleus of infected cells. Maribavir is active in vitro against
strains of CMV that are resistant to commonly used anti-CMV drugs.
Maribavir does not affect the maturation of viral DNA or affect the
viral DNA polymerase. The previous focus of clinical development of
maribavir as an anti-CMV agent was on the prevention of CMV disease
in transplant patients. Results from Phase 3 studies
indicated that maribavir at a dose of 100mg BID failed to meet its
efficacy endpoints. However, maribavir has demonstrated a
favorable safety and tolerability profile; across all clinical
studies to date, the most notable adverse event associated with
maribavir was taste disturbance. While Phase 3 studies of CMV
prophylaxis at the 100mg BID dose did not show sufficient activity
to prevent CMV disease, limited data from cases in which open-label
maribavir was used as CMV treatment suggest that higher doses may
provide clinical activity and clinical studies are
ongoing. The U.S. Food and Drug Administration (FDA) and the
European Commission have granted orphan drug designation to
maribavir for treatment of clinically significant cytomegalovirus
viremia and disease in at-risk patients, and the prevention and
treatment of cytomegalovirus disease in patients with impaired cell
mediated immunity, respectively.
About Cytomegalovirus
CMV is a member of the herpes virus group, which
includes the viruses that cause chicken pox, mononucleosis, herpes
labialis (cold sores), and herpes genitalis (genital herpes).
Like other herpesviruses, CMV has the ability to remain dormant in
the body for long periods of time. Human CMV infection rates
average between 50 percent and 85 percent of adults in the U.S. by
40 years of age, but in healthy adults causes little to no apparent
illness. However, in immunocompromised individuals including cancer
patients, HIV patients, and transplant patients, and in children
born with primary CMV infection, CMV can lead to serious disease or
death. Patients who are immunosuppressed following
hematopoietic stem cell (bone marrow) or solid organ
transplantation are at high risk of CMV infection. In these
patients, CMV can lead to severe conditions such as pneumonitis or
hepatitis, or to complications such as acute or chronic rejection
of a transplanted organ. While currently available systemic
anti-CMV agents are effective against the virus, their use is
limited by toxicities, most notably bone marrow suppression and
renal impairment.
About ViroPharma Incorporated
ViroPharma Incorporated is an international biopharmaceutical
company committed to developing and commercializing novel solutions
for physician specialists to address unmet medical needs of
patients living with diseases that have few, if any, clinical
therapeutic options, including C1 esterase inhibitor deficiency,
treatment of seizures in children and adolescents, adrenal
insufficiency, and C. difficile infection (CDI). Our goal is
to provide rewarding careers to employees, to create new standards
of care in the way serious diseases are treated, and to build
international partnerships with the patients, advocates, and
healthcare professionals we serve.
ViroPharma routinely posts information, including press
releases, which may be important to investors in the investor
relations and media sections of our company's website,
http://www.viropharma.com/. The company encourages investors to
consult these sections for more information on ViroPharma and our
business.
Forward-Looking Statements
Certain statements in this press release contain forward-looking
statements that involve a number of risks and uncertainties.
Various known and unknown risks, uncertainties and other factors
could lead to material differences between the actual future
results, financial situation, development or performance of the
company and the estimates given here. Forward-looking statements in
this press release include statements regarding potential
therapeutic indication and use of maribavir and regarding
maribavir's potential to address unmet medical needs. The
development and commercialization of pharmaceutical products is
subject to risks and uncertainties. The clinical data included in
this press release is preliminary and the study is ongoing. There
can be no assurance that the data generated at the end of the
studies will be consistent with the preliminary results described
in this press release. In addition, future data generated in
this study may elucidate trends not apparent at this time. There
can be no assurance that future studies with maribavir will
generate positive results or that maribavir will receive regulatory
approvals. The FDA or EMA may view data regarding maribavir as
insufficient or inconclusive, request additional data, require
additional clinical studies, limit any approved indications, or
deny the approval of maribavir. A description of risks and
uncertainties can be found in ViroPharma's Annual Report on Form
10-K for the fiscal year ended December 31,
2012, and 10-Q for the quarter ended March 31, 2013 filed with the Securities and
Exchange Commission. The forward-looking statements contained in
this press release are made as of the date hereof and may become
outdated over time. ViroPharma does not assume any responsibility
for updating any forward-looking statements. These forward-looking
statements should not be relied upon as representing our
assessments as of any date subsequent to the date of this press
release.
SOURCE ViroPharma Incorporated