| July 12
July 12 A radical new treatment for genetic
disorders has catapulted Alnylam Pharmaceuticals Inc
into the crosshairs of investors seeking the next breakthrough
name in biotechnology.
The challenge for the Cambridge, Massachusetts-based company
now is to prove that its 'gene silencing' technology can make
the leap from the laboratory to the doctor's office and eclipse
an alternative therapy already in use.
Investors, for now, are betting that it will. A steady drip
of positive trial data has helped to triple Alnylam's market
value to more than $2.7 billion in the space of 12 months. Eight
of the nine analysts covering the stock rate it "buy" or above.
For some, gene silencing could be a revolutionary treatment.
It works by 'switching off' the genes that cause disease, while
its potency derives from an ability to reproduce itself -
meaning a small dose can eliminate multiple targets.
"People know this mechanism works in a laboratory, but in
humans there is the challenge of delivering it to the
appropriate cell," said Marko Kozul, analyst at Leerink Swann,
an investment bank that specializes in healthcare.
"The question isn't one of mechanism. It's one of delivery."
Alnylam is testing its technology in conditions as varied as
liver cancer, respiratory tract infections, hemophilia and high
Its most advanced drug candidate, however, is a treatment
for amyloidosis, a rare condition caused by mutations in the
gene that produces the protein transthyterin (TTR). The mutation
leads to an abnormal build-up of proteins in various organs.
On Thursday, Alnylam's stock rose 16 percent after the
company said an early-stage trial of the therapy - known as
ALN-TTR - suppressed production of the protein. The drug was
administered subcutaneously, under the skin, ensuring its slow
Chief Executive John Maraganore told Reuters in an interview
that Alnylam was in talks with the U.S. Food and Drug
Administration (FDA) and wants to establish late-stage trial
goals which, if negotiated, would offer a more streamlined path
"There is recognition by the authorities of the significant
unmet need in this disease," said Maraganore, who invented and
led development of anti-clotting medicine Angiomax in a previous
job at Biogen Idec Inc.
Alnylam is not alone in fighting genetic disease. In terms
of getting a drug to market, the company is playing catch-up.
Often compared with Alnylam because of its focus on
gene-based drug technologies, Isis Pharmaceuticals Inc
had its drug, Kynamro, approved by the FDA in January. Its stock
price has more than doubled in the last year.
Kynamro is a treatment for a rare genetic disorder causing
dangerously high levels of 'bad' LDL (low-density lipoprotein)
cholesterol. Isis is also developing a different drug to treat
amyloidosis with its partner, GlaxoSmithKline Plc.
Isis uses a different technology to tackle genetic illness.
Known as antisense, it helps a drug bind to a specific gene in
order to interrupt the production of disease-causing proteins.
Alnylam's RNA interference, or RNAi - the scientific term
for gene silencing - works by turning off so-called messenger
RNAs, or mRNAs, which signal the production of similar proteins.
"One molecule of RNA can lead to silencing or destruction of
many RNA targets," said Daniel Anderson, a scientist based at
the Harvard-MIT Division of Health Sciences and Technology, who
holds a research grant from Alnylam.
"It recycles, basically, and keeps going. Perhaps there is
some debate in the field, but there is an argument to be made
that RNAi-based drugs do have the potential for increased
potency and longevity."
They might be safer, too. Edward Tenthoff, analyst at
investment bank Piper Jaffray, said that RNAi-based drugs can be
administered in comparatively small doses.
To date, the problem has been in the delivery. Alnylam's
gene silencing therapies, when tested intravenously, have been
degraded by enzymes in the blood before they could act.
Analysts say that, if this hurdle can be overcome, the
treatment could be more effective than antisense. The latest
data on subcutaneous delivery removed some of the uncertainty.
Alnylam said on Thursday that the subcutaneous GalNAc-siRNA
conjugate delivery platform would now be the primary approach
for development of its RNAi pipeline.
It is partnering with companies such as Arrowhead Research
Corp and Tekmira Pharmaceuticals Corp to
explore delivery techniques.
Tenthoff estimated that the subcutaneous version of the drug
could bring in as much as $4.1 billion in 2020. He estimated it
would reach market in 2018.
Alnylam has $450 million in cash, cash equivalents and
marketable securities - but no plans for deals.
"Boy! We have not seen anything in the outside world that
even comes close to being as exciting as investing in our
pipeline," Maraganore said. "We are going to stay pretty focused
on organic growth."
A year ago, the company's stock was worth $13.12. Even
before Thursday's spike, shares were trading at three times that
Maraganore, 50, said he hopes Alnylam can follow the same
upward trajectory as market darlings Alexion Pharmaceuticals Inc
and Regeneron Pharamaceuticals Inc.
"Those are two companies that have built enormous value by
virtue of commercializing breakthrough medicines with
significant retention of product rights and using partnerships,"
Regeneron, for example, has risen from relative obscurity to
a $23 billion company on the strength of its eye drug, Eylea.
If it can silence genes enough to treat just a few diseases,
Alnylam holds similar prospects, said Kozul at Leerink Swann.
"Alnylam could become a multi-billion-dollar market-cap
company even if it only targets liver-mediated disease."