Alnylam
Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics
company, announced today that the European Medicines Agency (EMA)
Committee for Orphan Medicinal Products (COMP) has adopted a positive
opinion recommending ALN-TTRsc for designation as an orphan medicinal
product for the treatment of transthyretin (TTR)-mediated amyloidosis
(ATTR).
“We are very pleased to have received a positive opinion from the EMA
COMP on our application for Orphan Drug Designation for ALN-TTRsc,” said
Saraswathy (Sara) Nochur, Ph.D., Senior Vice President, Regulatory
Affairs and Quality Assurance at Alnylam. “We believe RNAi therapeutics
represent a promising new approach for the treatment of ATTR, with the
potential to make a meaningful impact for patients with this progressive
and debilitating disease. We look forward to sharing Phase 2 clinical
data from our ALN-TTRsc program later in the year, and, assuming
continued positive results, we plan to advance to a Phase 3 pivotal
trial in ATTR patients with TTR cardiac amyloidosis by the end of the
year.”
ALN-TTRsc is currently in a pilot Phase 2 clinical trial for the
treatment of ATTR patients with TTR cardiac amyloidosis; this study is
aimed at evaluating the tolerability of ALN-TTRsc in approximately 15
patients. In addition, the study will assess preliminary clinical
activity as measured by knockdown of serum TTR levels and additional
exploratory tests, such as cardiac imaging (including echocardiography
and cardiac MRI), circulating cardiac biomarkers (NT-proBNP and
troponins T and I), 6-minute walk test, New York Heart Association
(NYHA) classification, and measures of heart failure symptoms and
quality of life (Kansas City Cardiomyopathy Questionnaire and EQ-5D
QOL). The company expects to present data from the Phase 2 trial in late
2014. Patients completing the Phase 2 trial will be eligible to
participate in an open-label extension (OLE) study for further
assessment of general tolerability and clinical activity with long-term
dosing; the ALN-TTRsc Phase 2 OLE study is expected to be initiated in
mid-2014. Assuming positive results, Alnylam expects to begin a Phase 3
trial in TTR cardiac amyloidosis patients by the end of 2014.
Orphan Drug Designation by the European Commission provides regulatory
and financial incentives for companies to develop and market therapies
that treat a life-threatening or chronically debilitating condition
affecting no more than five in 10,000 persons in the European Union
(EU), and where no satisfactory treatment is available. In addition to a
10-year period of marketing exclusivity in the EU after product
approval, Orphan Drug Designation provides incentives for companies
seeking protocol assistance from the EMA during the product development
phase, and direct access to centralized marketing authorization.
In January 2014, Genzyme and Alnylam formed an alliance to accelerate
and expand the development and commercialization of RNAi therapeutics
across the world. The alliance is structured as a multi-product
geographic alliance in the field of rare diseases. Alnylam retains
product rights in North America and Western Europe, while Genzyme
obtains the right to access Alnylam’s current “5x15” and future genetic
medicines pipeline in the rest of the world (ROW), including
co-development/co-commercialization and/or global product rights for
certain programs. In the case of ALN-TTRsc, Alnylam and Genzyme are
co-developing and co-commercializing the product in North America and
Western Europe, while Genzyme will advance the product in the ROW.
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 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 approved 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. Senile systemic amyloidosis (SSA) is a
non-hereditary form of TTR cardiac amyloidosis caused by idiopathic
deposition of wild-type TTR; its prevalence is generally unknown, but is
associated with advanced age. There is a significant need for novel
therapeutics to treat patients with TTR amyloid polyneuropathy and/or
cardiomyopathy.
About 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 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 as genetic medicines, including programs as
part of the company’s “Alnylam 5x15TM” product strategy.
Alnylam’s genetic medicine programs are RNAi therapeutics directed
toward genetically defined targets for the treatment of serious,
life-threatening diseases with limited treatment options for patients
and their caregivers. These include: patisiran (ALN-TTR02), an
intravenously delivered RNAi therapeutic targeting transthyretin (TTR)
for the treatment of TTR-mediated amyloidosis (ATTR) in patients with
familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously
delivered RNAi therapeutic targeting TTR for the treatment of ATTR in
patients with TTR cardiac amyloidosis, including familial amyloidotic
cardiomyopathy (FAC) and senile systemic amyloidosis (SSA); ALN-AT3, an
RNAi therapeutic targeting antithrombin (AT) for the treatment of
hemophilia and rare bleeding disorders (RBD); ALN-CC5, an RNAi
therapeutic targeting complement component C5 for the treatment of
complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting
aminolevulinate synthase-1 (ALAS-1) for the treatment of hepatic
porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an
RNAi therapeutic targeting PCSK9 for the treatment of
hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting
alpha-1-antitrypsin (AAT) for the treatment of AAT deficiency liver
disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the
treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an
RNAi therapeutic targeting angiopoietin-like 3 (ANGPTL3) for the
treatment of genetic forms of mixed hyperlipidemia and severe
hypertriglyceridemia; and other programs yet to be disclosed. As part of
its “Alnylam 5x15” strategy, as updated in early 2014, the company
expects to have six to seven genetic medicine product candidates in
clinical development - including at least two programs in Phase 3 and
five to six programs with human proof of concept - by the end of 2015.
The company’s demonstrated commitment to RNAi therapeutics has enabled
it to form major alliances with leading companies including Merck,
Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin,
Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and
Genzyme, a Sanofi company. In January 2014, Alnylam acquired Sirna
Therapeutics, a wholly owned subsidiary of Merck. In addition, Alnylam
holds an equity position in Regulus Therapeutics Inc., a company focused
on discovery, development, and commercialization of microRNA
therapeutics. Alnylam scientists and collaborators have published their
research on RNAi therapeutics in over 200 peer-reviewed papers,
including many in the world’s top scientific journals such as Nature,
Nature Medicine, Nature Biotechnology, Cell, the New
England Journal of Medicine, and The Lancet. 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,
Alnylam's expectations regarding its "Alnylam 5x15" product strategy,
Alnylam’s views with respect to the potential for RNAi therapeutics,
including ALN-TTRsc for the treatment TTR cardiac amyloidosis, its
expectations with respect to the timing and success of its clinical
trials, the expected timing of additional clinical trials, and its plans
regarding commercialization of RNAi therapeutics, 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 manage operating
expenses, 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, the outcome of litigation, and unexpected expenditures, as
well as those risks more fully discussed in the “Risk Factors” filed
with Alnylam’s most recent Annual Report on Form 10-K filed with the
Securities and Exchange Commission (SEC) and in other filings that
Alnylam makes with the SEC. 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 explicitly
disclaims any obligation to update any forward-looking statements.
Copyright Business Wire 2014