- Aims to Advance ALN-TTR02 into Phase III Pivotal Trial in
Transthyretin (TTR)-Mediated Amyloidosis (ATTR) Patients with Familial
Amyloidotic Polyneuropathy (FAP) by Late 2013; Phase II Data Expected in
Mid-2013 -
- Plans to Initiate Exploratory Phase II Study of ALN-TTRsc in ATTR
Patients with Familial Amyloidotic Cardiomyopathy (FAC) by Late 2013;
Phase I Data Expected in Mid-2013 -
- Expects to File Investigational New Drug (IND) Application for
ALN-AT3 in Hemophilia and Rare Bleeding Disorders in Mid-2013; Start
Phase I in Late 2013 -
- Expands “Alnylam 5x15” Pipeline with ALN-AS1, an RNAi Therapeutic
Targeting Aminolevulinate Synthase 1 (ALAS-1) for Treatment of Acute
Intermittent Porphyria -
- Guides to End 2012 with Approximately $225 Million in Cash -
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 6, 2013--
Alnylam
Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics
company, announced today its key “Alnylam 5x15™” pipeline and partner
program goals for 2013 through 2014.
“In 2012, we made tremendous progress in our RNAi therapeutic
development efforts with our ‘Alnylam 5x15’ product strategy focused on
genetically defined targets for diseases with limited treatment options
for patients and their caregivers. The next couple of years promise to
be transformative for Alnylam as we aim to advance our pipeline into
Phase III, report on key clinical data in multiple programs, and expand
the breadth our ‘5x15’ pipeline with additional clinical and
pre-clinical programs,” said John Maraganore, Ph.D., Chief Executive
Officer of Alnylam. “Specifically, we aim to advance what we believe to
be the industry leading effort in ATTR, with ALN-TTR02 starting a Phase
III trial for FAP patients and ALN-TTRsc entering a pilot Phase II trial
in FAC patients. In addition, we expect to report on clinical results
from Phase II and Phase I studies from these two programs respectively,
in mid-2013. Further, we are expanding our ‘5x15’ clinical pipeline with
ALN-AT3, a potential breakthrough therapy for hemophilia, including
hemophilia complicated by ‘inhibitors,’ and for other rare bleeding
disorders, where we expect to file an IND in mid-2013 and initiate a
Phase I study in late 2013. Finally, we are excited today to introduce a
new ‘Alnylam 5x15’ program – ALN-AS1 for the treatment of acute
intermittent porphyria, an ultra-rare genetic disease caused by loss of
function mutations in an enzyme in the heme biosynthesis pathway that
result in acute and/or recurrent life-threatening attacks with severe
abdominal pain, peripheral and autonomic neuropathy, and
neuropsychiatric manifestations. In aggregate, we believe that execution
on our ‘Alnylam 5x15’ programs and our ambitious goals for 2013 and
beyond will enable continued advancement of RNAi therapeutics as
innovative medicines for patients, resulting in value creation for our
shareholders.”
“Alnylam 5x15” Product Strategy Goals
-
Advance ALN-TTR02 into Phase III Pivotal Trial in Familial
Amyloidotic Polyneuropathy (FAP). ALN-TTR02 is an intravenously
delivered RNAi therapeutic targeting transthyretin (TTR) for the
treatment of TTR-mediated amyloidosis (ATTR).
-
Alnylam is currently conducting a Phase II study with ALN-TTR02 in
patients with ATTR. The Phase II study is an open-label,
multi-center, multi-dose, dose-escalation trial designed to enroll
approximately 20 ATTR patients. Patients are being enrolled into
cohorts of increasing doses and are receiving two doses of
ALN-TTR02 once every four weeks. The primary objectives of the
study are to evaluate the safety and tolerability of multiple
doses of ALN-TTR02 and to measure clinical activity based on
serial measurement of circulating serum TTR levels. The company
expects to report results from this trial in mid-2013.
-
Alnylam intends to initiate an open-label extension study in
mid-2013 for longer-term treatment of patients enrolled in the
Phase II study. The new extension study will include a number of
exploratory clinical endpoint measurements. The company intends to
provide periodic updates on results from the extension study
starting in 2014.
-
Assuming positive results from the Phase II study, the company
expects to initiate a Phase III pivotal trial of ALN-TTR02 in ATTR
patients with FAP in late 2013. FAP is a serious clinical
manifestation of ATTR that afflicts approximately 10,000 patients
worldwide. Alnylam will provide specific details on the trial
design following discussions with worldwide regulatory authorities.
-
Alnylam intends to directly commercialize ALN-TTR02 in North and
South America, Europe, and other parts of the world, and has
formed a partnership with Genzyme, a Sanofi company, to
commercialize the product in Japan and other Asian countries.
-
Move ALN-TTRsc through Phase I Study and into Pilot Phase II Trial
in Familial Amyloidotic Cardiomyopathy (FAC). ALN-TTRsc is an RNAi
therapeutic targeting TTR for the treatment of ATTR and utilizes the
company’s proprietary GalNAc-conjugate delivery approach enabling
subcutaneous dose administration.
-
Alnylam recently filed a Clinical Trial Application (CTA) with the
U.K. Medicines and Healthcare products Regulatory Agency (MHRA)
for ALN-TTRsc. The Phase I trial is designed as a randomized,
double-blind, placebo-controlled, single- and multi-dose, dose
escalation study, enrolling up to 40 healthy volunteer subjects.
The primary objective of the study is to evaluate the safety and
tolerability of ALN-TTRsc. In addition, the study will evaluate
clinical activity of ALN-TTRsc as measured by serum TTR levels.
Alnylam expects to begin dosing in this trial early in 2013 with
data mid-year.
-
Assuming positive results from the Phase I trial, Alnylam aims to
initiate an exploratory Phase II trial of ALN-TTRsc in ATTR
patients with FAC in late 2013 leading to the start of a Phase III
trial in FAC patients in 2014. FAC is a serious clinical
manifestation of ATTR that afflicts approximately 40,000 patients
worldwide.
-
As with ALN-TTR02, Alnylam intends to directly commercialize
ALN-TTRsc in North and South America, Europe, and other parts of
the world, and in partnership with Genzyme in Japan and other
Asian countries.
-
Expand “Alnylam 5x15” Clinical Pipeline with ALN-AT3, a Potential
Breakthrough Therapy for the Treatment of Hemophilia and Rare Bleeding
Disorders (RBD). Alnylam is developing ALN-AT3, an RNAi
therapeutic targeting antithrombin (AT) for the treatment of
hemophilia and RBD. This RNAi therapeutic utilizes the company’s
proprietary GalNAc-conjugate delivery approach enabling subcutaneous
dose administration. ALN-AT3 is a novel therapeutic approach aimed at
re-balancing the coagulation cascade and normalizing hemostasis in
severe hemophilia A and B patients, including patients with
“inhibitors” against their replacement factor. There are approximately
2,000 inhibitor patients in major markets with up to 5,000 patients
worldwide that define the greatest unmet need in hemophilia A and B.
In addition to hemophilia A and B which are characterized by a loss of
function in Factors VIII and IX respectively, ALN-AT3 has the
potential to treat RBD that are defined by deficiencies in other
clotting factors such as Factors II, V, VII, X, and XI. It is
estimated that there are approximately 1,000 RBD patients worldwide
with significant or severe bleeding complications where prophylaxis is
warranted. Alnylam plans to file an IND for ALN-AT3 in mid-2013 and to
initiate a Phase I study in late 2013. The company expects to report
data from this study in 2014. The company intends to directly
commercialize ALN-AT3 in North and South America, Europe, and other
parts of the world, and intends to seek a partner for this program in
Japan and other Asian territories.
-
Grow “Alnylam 5x15” Pipeline with ALN-AS1, a New Therapeutic
Strategy for the Treatment of Acute Intermittent Porphyria (AIP). Alnylam
announced today that it has designated ALN-AS1, an RNAi therapeutic
targeting aminolevulinate synthase 1 (ALAS-1) for the treatment of
acute intermittent porphyria (AIP), as a new program in its “Alnylam
5x15” product strategy. AIP is an ultra-rare genetic disease caused by
loss of function mutations in porphobilinogen deaminase (PBGD), an
enzyme in the heme biosynthesis pathway that can result in
accumulation of toxic heme precursors. Patients with AIP suffer from
acute and/or recurrent life-threatening attacks with severe abdominal
pain, peripheral and autonomic neuropathy, and neuropsychiatric
manifestations. Approximately 5,000 patients in the U.S. and Europe
suffer AIP attacks annually, and approximately 500 patients are
afflicted with recurrent debilitating attacks; patients with recurrent
attacks often include women in association with menses. ALN-AS1 is a
GalNAc conjugate targeting ALAS-1, a liver-expressed, rate-limiting
enzyme upstream of PBGD in the heme biosynthesis pathway. Inhibition
of ALAS-1 is known to reduce the accumulation of heme precursors that
cause the clinical manifestations of AIP. ALN-AS1 has the potential to
be a therapy for the treatment of acute porphyria attacks, as well as
a prophylactic approach for the prevention of recurrent attacks. The
company expects to identify a final development candidate by late 2013
and advance ALN-AS1 into the clinic in 2014. The company has generated
pre-clinical proof of concept data that will be presented at a
scientific meeting in mid-2013. The company intends to directly
commercialize ALN-AS1 in North and South America, Europe, and other
parts of the world, and intends to seek a partner for this program in
Japan and other Asian territories.
“Our ‘Alnylam 5x15’ product strategy is focused on potential
breakthrough medicines for high unmet need indications with concentrated
market access and strong patient advocacy,” said Barry Greene, President
and Chief Operating Officer of Alnylam. “With the progress we have made
in our pipeline, including plans to initiate our ALN-TTR02 Phase III
pivotal trial at the end of this year, we are now establishing a
commercial strategy to drive maximal value. Specifically, we plan to
directly commercialize our core ‘5x15’ products – ALN-TTR02, ALN-TTRsc,
ALN-AT3, and ALN-AS1 – in North and South America, Europe, and other
territories, while partnering for development expertise and market
access in Japan and other Asian markets. We will also continue to
advance other pipeline assets, including our RNAi therapeutic program
targeting PCSK9, with existing or future partnerships we aim to form.”
-
Advance Additional “Alnylam 5x15” Pipeline Programs through
Partnerships. Alnylam will continue to advance its additional
“Alnylam 5x15” programs, including: ALN-PCS, an RNAi therapeutic
targeting PCSK9 for the treatment of severe hypercholesterolemia;
ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of
hemoglobinopathies; and ALN-AAT, an RNAi therapeutic targeting the
mutant Z-allele in alpha-1-antitrypsin (AAT) deficiency for the
treatment of AAT deficiency-associated liver disease, amongst other
programs. Specifically, the company intends to advance these programs
with new partnerships it intends to form. Alnylam has also
elected to suspend further advancement of ALN-HPN, an RNAi therapeutic
targeting the hepcidin pathway for the treatment of refractory anemia,
in order to focus on other higher priority pipeline programs.
Partner Program Goals
-
Support Partner-Based Efforts for Advancement of Additional
Clinical-Stage RNAi Therapeutic Programs. Alnylam has completed a
Phase IIb clinical study with ALN-RSV01 for the treatment of
respiratory syncytial virus (RSV) infection in lung transplant
patients. The company has met with regulatory authorities in the U.S.
and Europe and, together with its partner Cubist, expects to
communicate an update on future plans in early 2013. ALN-RSV01 is
partnered with Kyowa Hakko in Japan and other major markets in Asia.
Alnylam will also continue to support its partner Ascletis as it
advances ALN-VSP, an RNAi therapeutic for the treatment of liver
cancers towards the clinic in China.
“Alnylam’s solid cash position, combined with our focused pipeline
efforts, ensure that our investments in 2013 will be directed toward the
highest value-creating activities that we believe exist within our
‘Alnylam 5x15’ pipeline,” said Michael Mason, Vice President, Finance
and Treasurer of Alnylam. “Today, we are guiding to end 2012 with
approximately $225 million in cash. We will provide financial guidance
for 2013 in connection with our year-end 2012 financial results in
February.”
Alnylam management will present a company overview at the 31st Annual
J.P. Morgan Healthcare Conference on Wednesday, January 9, 2013 at 8:00
a.m. PT (11:00 a.m. ET) at the Westin St. Francis Hotel in San
Francisco, Calif. A live audio webcast of the presentation will be
available on the News & Investors section of the company’s website, www.alnylam.com.
A replay of the presentation will be available on the Alnylam website
within 48 hours after the event.
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-AT3 for the treatment of hemophilia and rare
bleeding disorders (RBD), ALN-AS1 for the treatment of acute
intermittent porphyria, ALN-PCS for the treatment of severe
hypercholesterolemia, 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 partnered programs in clinical or development
stages, including ALN-RSV01 for the treatment of respiratory syncytial
virus (RSV) infection and ALN-VSP for the treatment of liver cancers.
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, Cubist, Ascletis, Monsanto and Genzyme. In addition,
Alnylam holds a significant equity position in Regulus Therapeutics
Inc., a company focused on discovery, development, and commercialization
of microRNA therapeutics. 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.
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 RNA (siRNA), 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-AT3 for the
treatment of hemophilia and rare bleeding disorders (RBD), ALN-AS1 for
the treatment of acute intermittent porphyria (AIP), ALN-PCS for the
treatment of severe hypercholesterolemia, ALN-TMP for the treatment of
hemoglobinopathies, and other programs. Alnylam intends to focus on
developing and commercializing certain programs from this product
strategy itself in North and South America, Europe, and other parts of
the world; these include ALN-TTR, ALN-AT3, and ALN-AS1; the company will
seek global development and commercial alliances for other programs.
About Transthyretin-Mediated Amyloidosis
Transthyretin (TTR)-mediated amyloidosis (ATTR) is an inherited,
progressively debilitating, and fatal disease caused by mutations in the
TTR gene. TTR protein is produced primarily in the liver and is normally
a carrier for thyroid hormone and retinol binding protein. 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. ATTR represents a major unmet medical need with
significant morbidity and mortality; familial amyloidotic polyneuropathy
(FAP) affects approximately 10,000 people worldwide and familial
amyloidotic cardiomyopathy (FAC) affects at least 40,000 people
worldwide. FAP patients have a life expectancy of five to 15 years from
symptom onset, and the only treatment options for early stage disease
are liver transplantation and tafamidis (approved in Europe). The mean
survival for FAC patients is approximately 2.5 years, and there are no
approved therapies. As a result, there is a significant need for novel
therapeutics to treat patients who have inherited mutations in the TTR
gene.
About Hemophilia and Rare Bleeding Disorders
Hemophilias are hereditary disorders caused by genetic deficiencies of
various blood clotting factors, resulting in recurrent bleeds into
joints, muscles, and other major internal organs. Hemophilia A is
defined by loss-of-function mutations in factor VIII, and there are
greater than 40,000 registered patients in the U.S. and E.U. Hemophilia
B, defined by loss-of-function mutations in factor IX, affects greater
than 9,500 registered patients in the U.S. and Europe. Standard
treatment for hemophilia patients involves replacement of the missing
clotting factor either as prophylaxis or on-demand therapy. However, a
significant number of hemophilia A patients will develop an antibody to
their replacement factor – a very serious complication; these
‘inhibitor’ patients become refractory to standard replacement therapy.
There are approximately 2,000 inhibitor patients in major markets and up
to 5,000 patients worldwide. Other rare bleeding disorders (RBD) are
defined by congenital deficiencies of other blood coagulation factors
including factors II, V, VII, X, and XI, with an estimated 1,000 RBD
patients worldwide in need of routine prophylaxis. There exists a
significant need for novel therapeutics to treat severe hemophilia
patients and patients with RBDs.
About Acute Intermittent Porphyria
Acute intermittent porphyria (AIP) is an ultra-rare autosomal dominant
disease caused by loss of function mutations in porphobilinogen
deaminase (PBGD), an enzyme in the heme biosynthesis pathway. Exposure
of AIP patients to certain drugs, dieting, or hormonal changes can
trigger strong induction of aminolevulinate synthase 1 (ALAS-1), another
enzyme in the heme biosynthesis pathway, which can lead to accumulation
of heme intermediates upstream of PBGD that precipitate attack symptoms.
Patients with AIP can suffer acute and/or recurrent life-threatening
attacks with severe abdominal pain, peripheral and autonomic neuropathy,
and neuropsychiatric manifestations, and possible death if left
untreated. Approximately 5,000 patients in the U.S. and Europe suffer
acute porphyria attacks annually, and approximately 500 patients are
afflicted with recurrent debilitating attacks. Treatment options for AIP
patients suffering from an acute attack are limited; some patients are
given intravenous heme analogues that must be administered through a
central venous catheter, but these have a slow onset and can result in
severe thrombophlebitis, iron overload and resistance to treatment over
time. Currently there is no approved prophylactic treatment available to
prevent recurrent attacks, which often occur monthly in women associated
with menses. There exists a significant need for therapies for AIP
patients.
About GalNAc Conjugates
GalNAc-siRNAs are designed to achieve targeted delivery of RNAi
therapeutics to hepatocytes through uptake by the asialoglycoprotein
receptor. Research findings demonstrate potent and durable target gene
silencing, as well as a wide therapeutic index, with subcutaneously
administered GalNAc-siRNAs from multiple ‘Alnylam 5x15’ programs.
Notably, GalNAc-siRNAs are being employed in Alnylam’s ALN-TTRsc and
ALN-AT3 RNAi therapeutic programs for the treatment of
transthyretin-mediated amyloidosis (ATTR) and hemophilia and rare
bleeding disorders, respectively, both of which the company expects to
have in clinical trials in 2013. GalNAc-siRNAs are a proprietary Alnylam
delivery platform.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam’s future
expectations, plans and prospects, including without limitation,
Alnylam’s expectations regarding its “Alnylam 5x15” product strategy,
Alnylam’s views with respect to the potential for RNAi therapeutics,
including ALN-TTR02 and ALN-TTRsc, ALN-AT3, ALN-AS1, ALN-PCS, ALN-TMP,
ALN-AAT, ALN-VSP, and ALN-RSV01, 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 IND or IND
equivalent applications and initiate clinical trials for ALN-TTR02,
ALN-TTRsc, ALN-AT3, and ALN-AS1, its expectations regarding reporting
data from its ongoing and planned clinical studies, including its
studies for ALN-TTR02, ALN-TTRsc, ALN-AT3, and ALN-AS1, its plans to
seek collaborations for its ALN-AT3, ALN-AS1, ALN-PCS, ALN-TMP, and
ALN-AAT programs, as well as other research programs and technologies,
and its expected cash position as of December 31, 2012, 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 and delivery approaches, successfully demonstrate
the efficacy and safety of its drug candidates, 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, Alnylam’s ability to enforce its patents against infringers
and defend its patent portfolio against challenges from third parties,
obtaining regulatory approval for products, competition from others
using technology similar to Alnylam’s and others developing products for
similar uses, Alnylam’s ability to obtain additional funding to support
its business activities and establish and maintain strategic business
alliances and new business initiatives, Alnylam’s dependence on third
parties for development, manufacture, marketing, sales and distribution
of products, and the successful defense of litigation, as well as those
risks more fully discussed in the “Risk Factors” section of its most
recent quarterly report on Form 10-Q 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.
Source: Alnylam Pharmaceuticals, Inc.
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice
President, Investor Relations and
Corporate Communications
or
Spectrum
Amanda
Sellers (Media), 202-955-6222 x2597
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