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Photo of
Brian Spear, Abbott
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Has
toxicogenomics finally turned the corner and
become mainstream? Concerns linger about
whether, and when, it's worth the extra
investment needed. Questions also remain about
how regulatory agencies will view genomic data.
But thanks to the availability of new tools such
as more advanced algorithms, whole genome
microarrays, and sufficient reference databases,
the field is finally having a significant effect
on drug development. |
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"One
of the most critical issues of toxicogenomics is
having a reference database constructed in a
highly controlled and standardized fashion,"
says Don Halbert, executive vice president of
R&D, Iconix Pharmaceuticals. The company's
database, DrugMatrix, built mostly on in vivo
rat studies, contains expression and other data
on more than 650 marketed drugs, failed drugs,
known toxicants, and biochemicals. Although
Halbert says companies are investing more in
toxicogenomics, it's still not routine. "There
are companies who still believe this type of
data is not going to help them enough to make
the investment worthwhile, but I think that's
changing." He adds that Iconix expects its
service business sales to almost double this
year and will add another pharmaceutical company
to their partner platform alliance. DrugMatrix
was built using GE Healthcare (formerly Amersham
Biosciences)'s CodeLink chips but was recently
extended to include whole genome data from
Affymetrix GeneChip arrays.
Gene
Logic has a large database of gene expression
profiles mainly from human, rat, and dog tissues
and cells. The company's ToxShield Suite
software provides predictive models in liver,
kidney, heart, and primary rat hepatocytes to
help to rank compounds. "Many companies have
started in toxicogenomics by using genomic
information to understand the mechanism of
toxicity they've seen with a compound," states
Donna Mendrick, vice president there. Gene Logic's
genomics division added more than 25 new
customers last year -- the largest number added
in one year since the company has been in
business.
Mendrick
says that when the FDA released its guidance
document in March 2005, outlining
pharmacogenomic data submissions, companies
started to look at "live" compounds in their
pipeline versus abandoned drugs because they
finally knew what type of data to submit. "Not
every company is embracing it, but it really
started to change what people were doing," she
says.
Abbott
uses toxicogenomics to identify compounds with
optimal attributes, early on. The company
generates gene-expression-based signatures for
specific toxicology endpoints using in vitro
models. Brian Spear, director, genomic and
proteomic technologies, says Abbott has
voluntarily submitted toxicogenomic data to the
FDA as part of the VGDS (Voluntary Genomic Data
Submission) program. Many companies are
concerned that data will be used later, when
they submit an IND or NDA. Spears says several
discussions with the agency about this concern
have been "quite illuminating." The company is
finding that the type of questions the agency
asks about the data is helpful.
Smaller
companies are also developing their own in-house
toxicogenomics methods. As a proof-of-principle,
researchers at Merck KGaA developed a hepatotox
chip with 550 genes, based on Illumina
technology, to look at liver toxicity in vivo. "We
found the data was very robust and of high
quality," says Philip Hewitt, head of
toxicogenomics there. He hopes to start using
this in all their pilot toxicology studies, to "convince
management it's something we should routinely
do." |
