Science & Technology Biotechnology
Potential Wonder Drugs
Chimerix discovers, develops and commercialises therapeutics that are active against a broad
range of viral diseases. The New Economy profiles a pioneering biotechnology company.
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The New Economy March–April 2008
In March 2002 a small biotechnology firm
revealed that an orally administered drug
they were developing had been found to
block smallpox infections in laboratory mice
and in human cells. At a time when the War
on Terror was just beginning, and a biological
attack seemed imminent, the US government
was extremely interested by this news. By
September 2003 they had awarded the company
behind the discovery, Chimerix, a four and a
half year $36.1m grant from the US National
Institute of Allergy and Infectious Diseases
(NIAID) of the National Institutes of Health (NIH).
Five years later, and the future looks bright
for Chimerix. The drug that so interests the
government, an antiviral called CMX001, is
currently undergoing blinded, randomised,
parallel–group, single–dose and multi–dose
placebo–controlled Phase I clinical studies to
evaluate its safety and pharmacokinetics.
So far the results look good. “The high oral
availability demonstrated by CMX001 in the
Phase I trial has validated the utility of the
company’s lipid technology, ProLipTag™ and
creates optimism for the potential of this drug
candidate,” says Dr. George Painter, Chimerix’s
President and CEO. “In addition to smallpox,
we believe that CMX001 has great potential in
treating other serious infections such as human
papillomavirus and cytomegalovirus.”
CMX001 was created by modifying a
drug known as cidofovir, that was already
commercially marketed in the United States
as Vistide® by Gilead Sciences. Cidofovir
is an approved drug for the treatment of
cytomegalovirus (CMV) infections that also has
been shown to be an effective therapy in primate
models of smallpox infection.
Cidofovir is administered by intravenous
infusion, and this makes it impractical for broad
distribution in the event of a smallpox outbreak.
The proprietary chemistry that Chimerix
carried out on clidofovir created a drug that
is orally available, more potent across all double
stranded DNA (dsDNA) viruses and less
toxic than cidofovir.
CMX001 is a lipid mimic of cidofovir formed by
linking a lipid hexadecyloxy–1–propanol, to the
phosphonate group of cidofovir. It’s designed to
cross cellular membranes by passive diffusion
(vida supra, Phospholipid Mimics Designed to
Facilitate Uptake in the Small Intestine).
In recent studies, antiviral assays showed that
the Chimerix compound was up to 250 times
more potent than cidofovir and active against
a variety of pox viruses including smallpox and
monkeypox. When given orally it was fully
effective in preventing mortality in mouse and
rabbit models of pox virus infection.
The fact that CMX001 and its variants have
the potential to combat viruses other than
small pox could add significantly to its market
value. “Innovative and promising antiviral
agents are needed to combat a growing number
of drug resistant viruses,” comments Dr Seth
Rudnick, one of Chimerix’s Board of Directors
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