Biomarkers are increasing the success rates of drug development and reducing costs by helping to identify failures earlier. They allow pharmaceutical companies to streamline clinical trials, make better decisions about drug candidates, and potentially develop personalized medicines to match patients with optimal treatments. While the initial costs of biomarker research and validation are high, biomarkers are expected to generate substantial savings over the long term through more efficient drug development and higher success rates.

1. Bi ph m D l p t M f t i g
Biopharm Development & Manufacturing
Bi m rk In
Biomarkers Increase
Biomarkers I re se
k e
R D Success Rates P
R&D Success R t s, Preempt
Success Rates, pt
Failures Reduce Cost
Failures,, & Reduce C t
il r ed
By Doug Graham
D
Drugs don’t debut quickly or cheaply. A new
y n
treatment develops over a decade or more, at
a cost just south of a billion dollars. Pharma
is business as well as science, and like any
industry, must routi
y routinely cope with pressures
imposed by economic uncertainly, increasing competition,
y
and tighter regulation.
Only recently has the global economy of genomics, proteomics, and bioinformat- potential threat to the pharmaceutical sec-
begun its long crawl to recovery, which some
y ics, empowering industry players to identify tor, Lucchini says. “The FDA and many com-
r,” e D
experts claim may grind to a halt soon. a greater number of complex targets than panies have taken the initiative in addressing
Healthcare reform, an Obama administration ever before. Much of this progress has been the high attrition rate in new treatment inno-
prime directive, will likely complicate the attributable to mighty advances in the tools vation by encouraging the use of biomarkers
pharma universe further still, as it will bring of the trade; high-throughput screening and modern technologies such as transcrip-
on ramifications highly significant to the methodologies and microarrays, and other tomics and histomics. These highly special-
industry.
y technologies that provide a bounty of new ized techniques can be quite expensive to
“To ’s pharmaceutical company faces a
Today data on a broader range of biological materi- deploy short-term, but long-term pay sizable
major safety efficacy challenge, coupled with al and processes. cost and efficiency dividends.”
a need to drastically reduce cost, streamline Ye pharmaceutical companies also operate
et
development, and reduce time to market,” under unusual constraint, hampering their A SOURCE OF PHARMA GROWTH
adds Stephane Lucchini, Ph.D, business ability to convert research findings into man- In recent years, the chanciness of pharma-
manager, Biovays, a b
r biotechnology contract ufacturable solutions viable for the con- ceutical research has encouraged more in
research organization (CRO) specializing in sumer market. Pharmaceutical business the way of specialist outsourcing and the
the expression, localization, and quantifica- models demand that more be done with deployment of solutions aimed at improv-
tion of biomarkers and in vitro assays, based fewer, better-
r r-optimized resources in o order ing the odds. A prime example of the lat-
in Marseilles, France. “By effectively meeting
r that safe treatments arrive at market with a ter — biomarkers (a.k.a. biological mark-
and managing such hurdles, companies greater expectation of success. The search ers) — are general substances used as
stand to produce more effective and safer for solutions to this end is endless. It is a indicators in pharmaceutical target valida-
treatments, and fundamentally increase principal driver in pharma’s quest to tion, candidate selection, research, and
their rates of success.” improve, but the road to perfection is often safety assessment.
The current pharma operat- bumpy. Some three quarters of new treat-
pyy t A biomarker is an extremely broad con-
ing environment is a two-edge ment, R&D budgeting is blown on mission cept (blood pressure, and cancer-screen-
r-
sword, Lucchini explains. On failures. Moreover, negative side ef
res. r effects ing PSA both qualify as biomarkers), with
the plus side, the mandate to sometimes force the withdraw of drugs after a tremendous number of current and pos-
perfect treatments for a con- release, irrespective of safety check expendi- sible applications. The maturing market
stantly expanding array of tures not too distant from the gross national for biological markers is strong, and get-
diseases and conditions products of some small countries. ting more muscular each year. The market
has been much-abetted “High clinical development costs and is expected to swell to U.S. $21 billion by
by giant steps in the fields declining new drug success rates pose a 2012, a figure exceeding that of 2005 by a
14 LifeScienceLeader.com
r. November 2009
Nov

2. Bi ph
Biopharm D l p t & Manufacturing
Development Manufacturing
M f t ig
growth factor of f r. This swift and h f y increase has been pro-
growth f
h f four Th f d hefty h b pro
p ues “Effective
ues. “Effective stratification is the key to accelera g clinical develop-
ff f h k y l ating l l develop
d l p
pelled by h
p ll d by the needs of the industries in which biomark are cur-
d of h i d i i hi h bi rkers cur ment and boosti g clinical trial success rates. Ove and above the need
t d b sting li i l t i l rates O er d b
t th d
rently d loyed, and b
ly deployed, d boosted b new market adoptio
deployed
dep d d by k adopt on.
d on to f d econom lly viable ways to guarantee m k success, such
find mically bl b ys gu market success h
“Th g
“The growing pop l i y of bi
The i g p pularity f biomarkers i phar
p k in ph rma i easily is ily approaches rep
pp h p
present a great leap forward into th realm of personal
g l pf di h
he l f personal-
p l
explained L hi i says. “Their use in early drug develo
explained,” Lucchini s
pl i d says “Th ir
Their i rl dr d lopment helps th l ized medicine, providing the right patient with th right dose.”
medicine iding ith he dose
streamline clinical development by determining whether a given drug
is reaching and affecting the molecular target in humans, delivering REGARDING ROI
findings that are comparable to clinical data, and providing a measura- Personalized medicine is a hot topic that’s quickly gaining currency in
ble endpoint that predicts desired or undesired clinical effects. Critical the wake of the Democratic victory in Washington and the subsequent
e a
ashington,
decisions, such as candidate selection, early proof of mechanism or push for healthcare reform. The idea, bottom line, is to match patients
proof of concept, dose ranging, patient stratification, and the assess- with medications likely to be optimally effective, minus nasty side
ment of development risks regarding safety, toxicity, and drug interac-
y y effects. Biomarkers will play an obvious role in the development of this
tions can be based on measurement of appropriate biomarkers that are customized approach to medicine, and pharma companies already
biologically and/or clinically validated.” employing them are poised to enjoy a significant advantage when the
Lucchini considers biomarkers a major source of pharmaceutical moment comes to bring personalized treatments to market.
industry business growth. In terms of actual science, most of this The soon-to-burgeon personalized medicine market is but one of
growth has been realized via proteomics — the science of proteins, and many potential payback areas for biomarker-
al -employing pharmas.
r-e
metabolomics — the science of metabolism. Diabetes research is an According to Lucchini, biomarker streamlining effects in targeted stud-
example of an area in which ies can generate savings of more
metabolomic biomarkers are espe- than 10%. That represents nearly
cially useful, as diabetes is a dys- “The initial cost of $10 million dollars given a new
function of metabolism. In years to biomarker investment is high.”
come, much research will be chan- Stephane Lucchini, Ph.D, Biovays
drug’s current development cost
of US $800-$900 million. But with
neled to the cure and control of this silver lining comes a cloud.
this chronic condition, now epi- “The initial cost of biomarker
investment is high,” Lucchini admits. “Much of the technology is still in
surely have a part to play in this critical endeavor. development, and you also have the validation phase. The develop-
ment of biomarkers is not different fundamentally than that of any
THE BIOMARKER MANTRA other technology. You start by building technology platforms, then you
ogy o
y
Thanks to the cost-saving and efficiency they offer, the R& role played
ving r R&D advance to specific applications. Since you are dealing in human
by biological markers in pharma is expanding at a pace equal to that of biology, you w have to invest in a range of applications and
y will
rket f optim
the of biomarker market itself. “Biomarkers help optimize candidate potential platforms. Through any one you risk encountering major
selection, and support critical decision-making in drug portfolio man- roadblocks.”
agement,” Lucchini says. “They enable more discriminating tests of T
function and toxicity during the early phases of the discovery and from the requirement for extremely expensive technology, coupled
h l y l d
development process, thus removing candidates unfit for the race with the nonnegotiable need for highly skilled specialists with years of
before they have a chance to compete. This not only saves massive experience, and employees well informed on cutting edge technolo-
amounts of time and unnecessary spending, it frees up resources for gies — are partly offset by the handsome advantages biomarkers pro-
future champions. The benefits are threefold: improved cost-effective- vide. These include more results with less risk, cost and time to mar-
ness, enhanced pipeline quality and decreased cycle times. So, as bio- ket, more chance of success with less likelihood of reproducibility, and
y
markers go, the mantra is; cheaper, better, faster.”
ra r r a significant improvement in quality, efficiency, an safety.
mprovement y y nd y
According to Lucchini, target or mechanism-specific biomarkers are “It’s extremely critical to translate biomarkers to diagnostics, par-
well suited for applications ranging from target validation and dose ticularly in terms of extending into clinical studies,” Lucchini cau-
testing to optimum dose selection, efficacy testing and safety and toler- tions. “One major advantage of biomarkers is that they provide
ability assessment. Disease-specific and outcome-specific biomarkers surrogate endpoints. Biomarkers are used in a broad range of appli-
are also employable as disease or patient biological markers in the cations, some consistent with conversion to a diagnostic, others incon-
stratification and identification of responders, an all-good situation sistent. When it is useful to include or exclude certain patient popula-
greatly enhancing proof-of-
oof- f-concept studies.
f tions, either before or after initial treatment, converting to a biomark-
“Disease-specific and outcome-specific biomarkers can be used to er can add significant value to a drug or make the difference between
establish new benchmarks in patient stratification,” Lucchini contin- success and failure in the clinic.”
erratum : more
November 2009
009 LifeScienceLeader.com
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