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RNAi for UNTREATABLE DISEASES |
New wave of RNAi-based drugs to
cure 'untreatable’ diseases
July 13, 2007
A new class of drugs that 'silence’
disease-causing mechanisms of hitherto
unaddressed disease conditions are set
to mark the next wave in medicine.
Major pharma companies have already
dropped their hats into what is called
RNAi (RNA interference) based drugs
that can switch off defective
mechanisms leading to a host of
disorders.
RNAi is a naturally occurring
mechanism within cells for selectively
silencing and regulating specific
genes. Short, double-stranded
ribonucleic acid molecules are found
to be capable of knocking down
virtually all genes.
Realising the potential of this
breakthrough discovery, many of the
leading companies involved in the drug
business either started in-house
development programs or acquiring
firms that have a stronger foothold in
the RNA technology, which formed the
basis for the Nobel Prize in medicine
awarded last year.
The latest spate of interest in RNAi
is triggered by Merck & Co's US$1.1
billion acquisition of Sirna
Therapeutics and its RNAi-based
therapeutics.
"We believe that RNAi could
significantly change the way in which
we go about discovering and developing
drugs, and could become a new way to
treat patients with unmet medical
needs," said Peter Kim, president,
Merck Research Laboratories.
Sirna's lead RNA development
candidate, Sirna-027, is currently
moving into phase II development for
the treatment of age related macular
degeneration as part of a
collaboration with Allergan.
In addition to the collaboration with
Allergan, Sirna has established a
strategic alliance with
GlaxoSmithKline for the development of
short-interfering RNA (siRNA)
compounds for the treatment of
respiratory diseases.
Toeing the line, the world’s top drug
maker Pfizer Inc acquired an exclusive
worldwide license of Quark Biotech,
Inc’s novel human gene RTP-801 and
other molecules. RTP-801 is involved
in the development of pathologic blood
vessels which accelerate the
progression of age-related macular
degeneration (AMD).
AMD is the leading cause of blindness
in the developed world affecting about
15 million Americans over the age of
50. The target for RTP-801 is
neovascular or wet AMD. Wet AMD is the
most devastating form of the disease
and occurs due to the formation of an
abnormal vascular network beneath the
retina of the eye. These blood vessels
are excessively leaky and lead to an
accumulation of fluid and blood
beneath and within the retina
resulting in a loss of visual acuity.
“Despite advances in research and the
availability of new treatment options,
there remains a need for new
approaches to improve the lives of
patients with AMD,” said Martin
Mackay, Ph.D., Pfizer senior vice
president Worldwide Research and
Technology. “We are excited about the
potential of RTP-801i to preserve
vision in patients with wet AD who
have an increased risk of progressive
eye damage and vision loss.”
Based on pre-clinical models, it is
believed that AMD can be treated by
blocking the expression of the TP-801
gene through RNA interference or RNAi.
Most recently, Roche has entered into
an alliance with Alnylam
Pharmaceuticals' to utilise its
technology platform for developing
RNAi therapeutics.
With this over US$1 billion
non-exclusive licensing agreement,
Roche will get access to broad
intellectual property (IP) and
knowledge, including fundamental,
chemistry and delivery.
Initially, the alliance will look into
developing drugs for certain forms of
cancer, respiratory and liver diseases
as well as disorders related to
metabolism such as diabetes, obesity
etc. The Swiss drug giant will pay
Alnylam US$331 million in up-front
cash payments and equity investment,
including 1.975 million shares of
Alnylam common stock that the Roche
Venture Fund agreed to purchase at
US$21.50 per share, representing just
less than 5 per cent of Alnylam's
outstanding common stock.
Roche will also pay Alnylam milestones
on products as they advance in
development and commercialisation, as
well as royalties on future sales of
commercial products. Further, Roche
may pay Alnylam field-expansion
payments to increase the number of
therapeutic areas.
The transaction includes Roche's
acquisition of Alnylam's European
research site in Kulmbach, Germany
dedicated to RNAi therapeutics
discovery as a new Center of
Excellence for RNAi therapeutics
within Roche's global research
organisation.
In 2005, Novartis acquired a 20 per
cent stake in Alnylam and is
collaborating with the company on the
discovery of RNAi therapeutics for the
treatment of a number of disease
areas, including influenza. Alnylam
also has agreements with Medtronic and
Biogen Idec under which the companies
are pursuing RNAi therapeutics for
neurodegenerative disorders and
progressive multifocal
leukoencephalopathy, respectively.
Another recent colloboration happened
in this area is between AstraZeneca
and Silence Therapeutics. The
three-year program aims to develop
siRNA molecules against up to five
specific drug targets in the
respiratory field.
Silence is entitled with
identification and optimisation of the
drug targets while AstraZeneca will
retain full responsibility for
clinical development and
commercialisation.
Under the terms agreed upon, Silence
will receive clinical development and
commercial milestone payments of up to
£200 million (approximately US$400
million), in addition to royalties on
product sales from the Anglo-Swedish
drug giant.
AstraZeneca will be provided with a
licence to Silence's siRNA technology
in return for an initial access fee of
£7.5 million (approximately US$15
million), comprising a payment of £2.5
million (approximately US$5 million),
plus an equity investment of £5
million (approximately US$10 million).
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