Alnylam’s RNAi drug delivery holds the promise of becoming the new
face of disease control and treatment. Alnylam, by making investments and
fending off lawsuits and bad press, has positioned itself as a frontrunner in
this category. Alnylam's RNAi drug delivery works like this: it “runs interference”
with RNA to prevent disease, by selectively shutting off harmful genes. Disease
targets include genetic disorder ATTR (transthyretin-mediated amyloidosis)
and RSV (respiratory syncytial virus), a pediatric viral
infection. Its other R&D programs target oncology,
cardiovascular and neurological disorders. Press release about Phase I clinical
trial commencement with ALN-TTR02 is
below.
Source: www.alnylam,com;
date released: March 19, 2012
CAMBRIDGE,
Mass.--(BUSINESS WIRE)--Alnylam
Pharmaceuticals, Inc. (Nasdaq:
ALNY), a leading RNAi therapeutics company, announced today that it has
initiated dosing in its Phase I clinical trial with ALN-TTR02, an RNAi
therapeutic targeting the transthyretin (TTR) gene for the treatment of
TTR-mediated amyloidosis (ATTR). The study is aimed at evaluating the safety
and tolerability of ALN-TTR02 in healthy volunteers. In addition, the study
will evaluate the clinical activity of ALN-TTR02 based on measurements of serum
levels of TTR, the disease-causing protein in patients with ATTR. ALN-TTR02
utilizes the company’s proprietary second-generation lipid nanoparticle (LNP)
technology using the “MC3” lipid. Alnylam expects to present data from this
study in the third quarter of 2012.
“ALN-TTR02 utilizes
our proprietary second-generation LNP technology which has shown significant
potency improvements in both pre-clinical and clinical studies. We very much
look forward to our expected reporting of TTR knockdown data from the Phase I
study in the third quarter of this year.”
“Advancement
of ALN-TTR02 into the clinic is an important milestone in our ‘Alnylam 5x15’
product strategy. Indeed, ALN-TTR02 is our lead program in this effort and we
expect to initiate a Phase II trial later this year, followed by a pivotal
trial starting in 2013,” said Akshay K. Vaishnaw, M.D., Ph.D., Senior Vice
President and Chief Medical Officer of Alnylam. “ALN-TTR02 utilizes our
proprietary second-generation LNP technology which has shown significant
potency improvements in both pre-clinical and clinical studies. We very much
look forward to our expected reporting of TTR knockdown data from the Phase I
study in the third quarter of this year.”
“RNAi
therapeutics represent a novel and exciting approach for the treatment of ATTR,
as this new drug modality has the potential to make a meaningful impact in the
treatment of this devastating disease. I am very encouraged by the recent
results from Alnylam’s Phase I study with ALN-TTR01 which showed knockdown in
serum levels of TTR, the pathogenic protein in this disease. These results are
important because we believe TTR suppression has the potential of halting or
even reversing disease pathology in ATTR patients,” said Teresa Coelho, M.D.,
Director, Unidade Clinica de Paramiloidose. “I support the continued
advancement of this innovative medicine, and look forward to results from this
new study, as well as additional clinical studies.”
The Phase I
trial of ALN-TTR02 is being conducted in the U.K. as a randomized, single-blind,
placebo-controlled, single-ascending dose study, enrolling approximately 32
healthy volunteer subjects. The primary objective of the study is to evaluate
the safety and tolerability of a single dose of ALN-TTR02, with subjects being
enrolled into five sequential cohorts of increasing doses ranging from 0.01 to
0.50 mg/kg. Secondary objectives include serial measurement of circulating TTR
serum levels through at least day 56 following a single dose. Additional
secondary objectives include plasma and urine pharmacokinetics of ALN-TTR02.
About
Transthyretin-Mediated Amyloidosis
Transthyretin
(TTR)-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by
mutations in the TTR gene. TTR protein is produced primarily in the liver and
is normally a carrier for thyroid hormones and retinol binding proteins.
Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body
organs and tissue such as the peripheral nerves and heart, resulting in
intractable peripheral sensory neuropathy, autonomic neuropathy, and/or
cardiomyopathy. In its severest form, ATTR represents a major unmet medical
need with significant morbidity and mortality as an orphan disease; FAP
(familial amyloidotic polyneuropathy) affects approximately 10,000 people worldwide
and FAC (familial amyloidotic cardiomyopathy) affects at least 40,000 people
worldwide. ATTR patients with FAP have a mean life expectancy of five to 15
years from symptom onset and the only treatment option is liver
transplantation; as a result there is a significant need for novel therapeutics
to treat patients who have inherited mutations in the TTR gene.
About
ALN-TTR Program
ALN-TTR is a
systemically delivered RNAi therapeutic being developed for the treatment of
ATTR. Pre-clinical
studies have shown that treatment with Alnylam’s first-generation
product candidate, ALN-TTR01, resulted in both prevention and regression of
pathogenic TTR deposits in peripheral tissues including dorsal root ganglia,
sciatic nerve, stomach, and intestines in animal models. In November 2011,
Alnylam reported positive preliminary clinical results from its ALN-TTR01 Phase
I, multinational clinical trial showing that ALN-TTR01 was generally safe and
well tolerated and resulted in statistically significant lowering of TTR serum
levels in ATTR patients. Alnylam has completed enrollment in the ALN-TTR01
Phase I trial and expects to present final data in the first half of 2012. In
March 2012, Alnylam initiated a Phase I clinical trial with ALN-TTR02, its
second-generation ATTR therapeutic candidate which utilizes an improved
second-generation LNP formulation with the “MC3” lipid. In pre-clinical
studies, this second-generation LNP technology demonstrated an over 10-fold
improvement in potency. Data from the ALN-TTR02 Phase I trial are expected in
the third quarter of 2012. In addition, Alnylam plans to start a Phase II
multi-dose clinical study of ALN-TTR02 in ATTR patients in the second half of
2012 and, assuming positive results, expects to initiate a pivotal trial with
ALN-TTR02 in 2013. Alnylam is also advancing ALN-TTRsc, which utilizes a
GalNAc-conjugate delivery approach and subcutaneous dose administration.
Alnylam plans to file an investigational new drug (IND) application or IND
equivalent for ALN-TTRsc in the second half of 2012, with data expected in the
first half of 2013. ALN-TTRsc has the potential to provide product
differentiation and expansion in the ATTR indication.
About RNA
Interference (RNAi)
RNAi (RNA
interference) is a revolution in biology, representing a breakthrough in
understanding how genes are turned on and off in cells, and a completely new
approach to drug discovery and development. Its discovery has been heralded as
“a major scientific breakthrough that happens once every decade or so,” and
represents one of the most promising and rapidly advancing frontiers in biology
and drug discovery today which was awarded the 2006 Nobel Prize for Physiology
or Medicine. RNAi is a natural process of gene silencing that occurs in
organisms ranging from plants to mammals. By harnessing the natural biological
process of RNAi occurring in our cells, the creation of a major new class of
medicines, known as RNAi therapeutics, is on the horizon. Small interfering
RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam’s RNAi
therapeutic platform, target the cause of diseases by potently silencing
specific mRNAs, thereby preventing disease-causing proteins from being made.
RNAi therapeutics have the potential to treat disease and help patients in a
fundamentally new way.
About
“Alnylam 5x15™”
The “Alnylam
5x15” strategy, launched in January 2011, establishes a path for development
and commercialization of novel RNAi therapeutics to address genetically defined
diseases with high unmet medical need. Products arising from this initiative
share several key characteristics including: a genetically defined target and
disease; the potential to have a major impact in a high unmet need population;
the ability to leverage the existing Alnylam RNAi delivery platform; the opportunity
to monitor an early biomarker in Phase I clinical trials for human proof of
concept; and the existence of clinically relevant endpoints for the filing of a
new drug application (NDA) with a focused patient database and possible
accelerated paths for commercialization. By the end of 2015, the company
expects to have five such RNAi therapeutic programs in clinical development,
including programs in advanced stages, on its own or with a partner. The
“Alnylam 5x15” programs include ALN-TTR for the treatment of
transthyretin-mediated amyloidosis (ATTR), ALN-APC for the treatment of
hemophilia, ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN
for the treatment of refractory anemia, and ALN-TMP for the treatment of
hemoglobinopathies. Alnylam intends to focus on developing and commercializing
certain programs from this product strategy itself in the United States and
potentially certain other countries; the company will seek development and
commercial alliances for other core programs both in the United States and in
other global territories.
About
Alnylam Pharmaceuticals
Alnylam is a
biopharmaceutical company developing novel therapeutics based on RNA
interference, or RNAi. The company is leading the translation of RNAi as a new
class of innovative medicines with a core focus on RNAi therapeutics for the
treatment of genetically defined diseases, including ALN-TTR for the treatment
of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of
severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia,
ALN-APC for the treatment of hemophilia, and ALN-TMP for the treatment of
hemoglobinopathies. As part of its “Alnylam 5x15TM” strategy,
the company expects to have five RNAi therapeutic products for genetically defined
diseases in clinical development, including programs in advanced stages, on its
own or with a partner by the end of 2015. Alnylam has additional partner-based
programs in clinical or development stages, including ALN-RSV01 for the
treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the
treatment of liver cancers, and ALN-HTT for the treatment of Huntington’s
disease. The company’s leadership position on RNAi therapeutics and
intellectual property have enabled it to form major alliances with leading
companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda,
Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus
Therapeutics Inc., a company focused on discovery, development, and
commercialization of microRNA therapeutics; Regulus has formed partnerships
with GlaxoSmithKline and Sanofi. Alnylam has also formed Alnylam
Biotherapeutics, a division of the company focused on the development of RNAi
technologies for applications in biologics manufacturing, including recombinant
proteins and monoclonal antibodies. Alnylam’s VaxiRNA™ platform applies RNAi
technology to improve the manufacturing processes for vaccines; GlaxoSmithKline
is a collaborator in this effort. Alnylam scientists and collaborators have
published their research on RNAi therapeutics in over 100 peer-reviewed papers,
including many in the world’s top scientific journals such as Nature, Nature
Medicine, Nature Biotechnology, and Cell. Founded in 2002,
Alnylam maintains headquarters in Cambridge, Massachusetts. For more
information, please visit www.alnylam.com.
Alnylam
Forward-Looking Statements
Various
statements in this release concerning Alnylam’s future expectations, plans and
prospects, including without limitation, statements regarding Alnylam's views
with respect to the potential for RNAi therapeutics, including ALN-TTR02 and
ALN-TTRsc, its expectations with respect to the timing and success of its
clinical and pre-clinical trials, the expected timing of regulatory filings,
including its plan to file an IND or IND equivalent application for ALN-TTRsc
and to initiate clinical trials for ALN-TTR02 and ALN-TTRsc, its expectations
regarding the reporting of data from its ALN-TTR01, ALN-TTR02 and ALN-TTRsc
clinical trials, and Alnylam’s expectations regarding its “Alnylam 5x15”
product strategy, constitute forward-looking statements for the purposes of the
safe harbor provisions under The Private Securities Litigation Reform Act of
1995. Actual results may differ materially from those indicated by these
forward-looking statements as a result of various important factors, including,
without limitation, Alnylam’s ability to discover and develop novel drug
candidates, successfully demonstrate the efficacy and safety of its drug
candidates, including ALN-TTR02 and ALN-TTRsc, the pre-clinical and clinical
results for its product candidates, which may not support further development
of product candidates, actions of regulatory agencies, which may affect the
initiation, timing and progress of clinical trials, obtaining, maintaining and
protecting intellectual property, obtaining regulatory approval for products,
competition from others using technology similar to Alnylam’s and others
developing products for similar uses, and Alnylam’s ability to establish and
maintain strategic business alliances and new business initiatives, as well as
those risks more fully discussed in the “Risk Factors” section of its most
recent annual report on Form 10-K on file with the Securities and Exchange
Commission. In addition, any forward-looking statements represent Alnylam’s
views only as of today and should not be relied upon as representing its views
as of any subsequent date. Alnylam does not assume any obligation to update any
forward-looking statements.
No comments:
Post a Comment