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Everything old is new again
April 2012
SHARING OPTIONS:
Viagra. Everyone's heard of it. Everyone knows what it does.
But most people probably don't realize that sildenafil citrate began its life
intended for another purpose before it was repurposed into the blockbuster that
it is today. When the compound was found to be unsuccessful as an
anti-hypertensive agent in Phase I trials, Pfizer Inc. found success in
switching the drug to the treatment of erectile dysfunction.
Long before that success, other compounds have gone on to
other lives; a commonly cited example is thalidomide, originally used as a
sedative to treat morning sickness in pregnant women, and then went on to be used
as a treatment for multiple myeloma and erthema nodosum leprosum. Another
success: finasteride, originally approved for benign prostate hyperplasia, now
also approved to treat male pattern baldness as the active ingredient in
Propecia.
Companies have likely invested millions of dollars and
countless hours in the development process. Bringing completely new drugs to
market, through all the stages of human trials and regulatory approvals, can
take years. Inherent in this process is risk.
"A repositioned drug has the same chances of success as an
original drug in meeting efficacy end points. There is nothing inherently
different about repositioned drugs to make them less able to succeed due to
efficacy," says Dr. Andreas Persidis, co-founder and CEO of Biovista Inc., a
private drug development services company that is headquartered in
Charlottesville, Va. "However, they lack the risks of original drugs, which is
a major advantage of repositioning."
And, adds Frost & Sullivan Technical Insight Research
Analyst Ruplekha Choudhurie,
How are they chosen?
According to Cauwenberghe, two main selection criteria for
drug repurposing candidates can be cited: known compounds with new targets in
the first place, and known mechanisms with new indications in the second place.
According to Persidis, four key trends are paving the path
in drug repositioning.
Second, generics pressures: Generics companies are becoming
more aggressive, and they are also entering the new drug arena themselves (e.g., Teva acquiring Cephalon). This
means that both pharmas and generics companies are looking to repositioning as
a way to distance themselves from each other.
"Repositioning allows an increase in Phase II starts leading
to more drugs entering the clinic at any given time," he says. "In addition,
repositioning may reveal new biology in a disease, leading to innovation in therapeutic
approaches. A good example is Gleevec, whose previously unexpected off-target
pharmacology has led to it being tried in a number of non-cancer indications,
including spongyloarthritis and others."
Last, Persidis says, but certainly on par with the other
factors, are competitor adjacency threats.
"A good example is Enbrel, which was repositioned by BDC in
sciatica, and then acquired by Cephalon for about $40 million upfront and about
$200 million in milestones in 2009-2010," he adds. "Amgen, the owner of Enbrel,
does not have rights now in the use of their drug in this new major market, and
this vulnerability is prevalent in a number of well-known companies, because
they seem to choose to ignore the possibility that another group may be able to
find something about their drug that they didn't know."
What are the good
disease targets?
Frost and Sullivan's Choudhurie singles out two targets for
further growth in repurposing; both diseases are complex and treatments for
both are highly sought-after around the globe.
Not without impact is the rising tide of medical needs in
the aging baby boomer population. Choudhurie's Frost & Sullivan colleague Cauwenberghe
says it's hard to choose targets specifically, but we can generalize about
impacts in the future.
"On the other hand," she points out, "rare diseases have
been also targeted through numerous projects."
Choudhurie agrees: "Another advantage of repositioning is
that diseases with a high unmet need can be targeted with these drugs that are
already in the market," she says.
Some are not as exuberant about the potential of this method
of discovery for attacking rare diseases. Again, limited resources juxtaposed
against a small population who can benefit makes the math sometimes tricky,
even if expensive early steps have been taken.
Failures … or
opportunities?
"A recent example of a not successful one is Dimebon, a
cough suppressant that was repositioned in Alzheimer's disease by Medivation
and Pfizer, but failed to meet its Phase III end-points," says Persidis.
"However, there is believed to be more extensive pharmacology on this drug,
creating important possibilities for it to be rescued and re-repositioned in
other diseases."
To be sure, rapid technological advances and new business
strategies in the recent past have changed the game rapidly since the time of
thalidomide.
Says Cauwenberghe: "On that note, it is important to
highlight the fact that during the past five years, innovation in the
biopharmaceutical industry has helped counter rising development costs, and
stagnant product output has become a leading cause for drug repurposing."
With little new on drug companies' plates for one reason or
another, new therapies have to come from somewhere.
"Two other relevant reasons rely on the need to expand
product pipelines with new projects, as well as the increasing of the pool of
potential compounds abandoned due to strategic reasons," she adds.
New technologies and methods for sharing information play a
large role.
"Companies have been encouraged to emerge from another
perspective, by expanding their technology platforms for identifying new
indications," Cauwenberghe explains. "This has led to the success of several
projects committed to the development of proprietary pipelines of candidates,
while reducing the related risks and timelines in further clinical development.
Moreover, current business models and technology platforms promote the public
generation of proof-of-concept clinical data to share efforts for repositioning
purposes."
An example of those new business models is the one being
developed by Transparency Life Sciences (TLS), which is developing repurposed
drugs based on an open-innovation and crowdsourcing model.
The relatively new company introduced its crowdsourcing
model in beta on Jan. 31, and is inviting interested individuals to participate
in the design of the protocol for a Phase II trial of lisinopril in MS. It
hopes that opening up the study design in this way will allow for collaboration
in ways not before thought possible.
"The paradigm shift around drug repositioning necessarily
derives a change in the current business models utilized by pharmaceutical and
biotechnology industry," concludes Cauwenberghe. "In particular, pharmaceutical
companies have to face the challenge to transform their blockbuster model
toward a more accurate, flexible and cost-effective model that involves the
development of therapeutics for new prospect indications. Indeed, a myriad of
small companies have started to play new roles in the biopharmaceutical market.
Their innovative capacity, as well as their constant nutrition with academic
fields, becomes these companies as strategic players, leading to a novel trend
of M&A activities and licensing agreements."
Code: E041230 Back |
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