– Once-Monthly, Subcutaneous Fitusiran Achieves
Median Annualized Bleeding Rate (ABR) of 1.0, with Median
Observation Period of 5.7 Months –
– Fitusiran Generally Well Tolerated with No
Thromboembolic Events –
– Alnylam On Track to Initiate Phase 3 Program
in Early 2017 –
– Management to Discuss New Clinical Data in
Webcast Conference Call Today, Sunday, December 4, at 1:00 p.m. ET
–
Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading RNAi
therapeutics company today announced new positive results from its
ongoing Phase 2 open-label extension (OLE) study with fitusiran, an
investigational RNAi therapeutic, in patients with hemophilia A or
B without inhibitors. These results were presented today in a
poster at the 58th Annual Meeting of the American Society of
Hematology (ASH), held December 3 – 6, 2016 in San Diego,
California.
New clinical data showed that once-monthly subcutaneous
administration of fitusiran achieved consistent lowering of AT and
increases in thrombin generation, resulting in a median estimated
annualized bleeding rate (ABR) of 1.0 in patients with hemophilia A
or B without inhibitors. In addition, fitusiran was generally well
tolerated, with no thromboembolic events or laboratory evidence of
pathologic clot formation through the data cut-off date.
“We are encouraged by the longer-term tolerability data and
clinical activity of fitusiran, with a median ABR of 1.0 in
patients with hemophilia A or B with up to 14 months of continuous
dosing. These data, combined with positive results we reported
yesterday in hemophilia patients with inhibitors, continue to
highlight what we believe to be the significant potential of
fitusiran as a once-monthly subcutaneous investigational medicine
for prevention of bleeding in people with hemophilia and RBD,” said
Akin Akinc, Ph.D., Vice President and General Manager, Fitusiran.
“Going forward, we expect to present data from the ongoing Phase 2
OLE study at least once per year. Meanwhile, we’re aiming to
initiate our Phase 3 clinical program in early 2017 to generate
definitive evidence for fitusiran efficacy and safety in support of
potential regulatory approvals.”
The Phase 2 OLE study results as of the data cut-off date of
October 6, 2016 included 16 hemophilia A or B patients without
inhibitors. All patients were previously enrolled in the fitusiran
Phase 1 study, receiving 3 weekly or 3 monthly subcutaneous doses
ranging from 45 micrograms per kilogram (mcg/kg) to 1800 mcg/kg. In
the Phase 2 OLE study, fitusiran was administered subcutaneously
once-monthly at two fixed dose levels, 50 mg (N=8) and 80 mg (N=8),
with patients receiving up to 14 months of continuous dosing. Both
dose levels achieved mean AT lowering of approximately 80 percent
and mean increases in thrombin generation levels approaching the
lower end of the range observed in normal healthy individuals in
Part A of the Phase 1 study. In an exploratory post hoc analysis of
bleed events, fitusiran achieved a median overall ABR of 1.0, over
a median observation period of 5.7 months, compared to a median
pre-study ABR of 4.0. In the study, 8 out of 16 patients (50
percent) reported zero bleeds and 11 out of 16 patients (69
percent) experienced zero spontaneous bleeds.
The data reported from the Phase 2 OLE study also includes the
first reported elective surgical procedure in a fitusiran-treated
patient. Specifically, a patient with severe hemophilia A receiving
50 mg monthly fitusiran underwent an elective septoplasty
procedure. Prior to the surgical procedure, the patient’s AT levels
were 13 percent relative to baseline. As reported by the
investigator via personal communication, the cumulative
periprocedural utilization of recombinant factor VIII was
approximately 20 percent of that typically used by the investigator
for this type of surgery in a severe hemophilia A patient. Based on
the International Society of Thrombosis and Haemostasis (ISTH)
hemostasis efficacy score, the investigator rated hemostasis
control in the intra-operative, 24 hours post-operative, and 7 days
post-operative periods as all being “excellent”.
Fitusiran was generally well tolerated with the longest period
of exposure of up to 14 months of continuous treatment. All adverse
events (AEs) were mild or moderate in severity, with the most
common AEs consisting of mild injection site reactions (ISRs) in 4
out of 16 patients (25 percent). Asymptomatic and reversible
alanine aminotransferase (ALT) increases greater than 3 times the
upper limit of normal (ULN), without concurrent elevations in
bilirubin greater than 2 times ULN, were observed in three patients
in the OLE study, all of whom have medical history of hepatitis C
infection (HCV). All breakthrough bleeding events were successfully
managed with replacement factor. There were no drug-related serious
adverse events (SAEs), no discontinuations due to AEs in the OLE
study, and no thromboembolic events or laboratory evidence of
pathologic clot formation through the data cut-off date.
To view the fitusiran clinical results described in this press
release, please visit www.alnylam.com/capella.
Conference Call Information
Alnylam management will discuss these clinical data in a webcast
conference call today, Sunday, December
4, at 1:00 p.m. ET. A slide presentation will also be
available on the Investors page of the company's
website, www.alnylam.com, to accompany the conference call. To
access the call, please dial 877-312-7507 (domestic) or
631-813-4828 (international) five minutes prior to the start time
and refer to conference ID 28671881. A replay of the call will be
available beginning at 4:00 p.m. ET. To access the replay,
please dial 855-859-2056 (domestic) or 404-537-3406
(international), and refer to conference ID 28671881.
About Fitusiran
Fitusiran is a subcutaneously administered, investigational RNAi
therapeutic targeting antithrombin (AT) for the treatment of
hemophilia A and B and rare bleeding disorders (RBD) currently in
early stage clinical development. Fitusiran is designed to lower
levels of AT with the goal of promoting sufficient thrombin
generation to restore hemostasis and prevent bleeding in patients
with hemophilia and RBD. AT, also known as "antithrombin III" and
"SERPINC1" is a liver-expressed plasma protein and member of the
"serpin" family of proteins that acts by inactivating thrombin and
other coagulation factors. AT plays a key role in normal hemostasis
by helping to limit the process of fibrin clot formation. However,
in hemophilia, insufficient thrombin generation results in impaired
fibrin clot formation. Lowering AT in the hemophilia setting may
promote the generation of sufficient levels of thrombin needed to
form an effective fibrin clot and prevent bleeding. This rationale
is supported by human genetic data suggesting that co-inheritance
of thrombophilic mutations, including AT deficiency, may ameliorate
bleeding in hemophilia. Lowering of AT is a unique and innovative
strategy for restoring hemostasis in people with hemophilia.
Fitusiran utilizes Alnylam's ESC-GalNAc conjugate technology, which
enables subcutaneous dosing with increased potency and durability
and a wide therapeutic index.
Sanofi Genzyme Alliance
In January 2014, Alnylam and Sanofi Genzyme, the specialty care
global business unit of Sanofi, 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 the United States, Canada and
Western Europe, while Sanofi Genzyme obtained the right to access
certain programs in Alnylam's current and future Genetic Medicines
pipeline in the rest of the world through the end of 2019, together
with certain broader co-development/co-commercialization rights and
global rights for certain products. Sanofi Genzyme has elected to
opt in to co-develop (through Sanofi R&D) and co-commercialize
fitusiran in the United States, Canada and Western Europe, in
addition to developing and commercializing fitusiran in its rest of
world territories.
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. Alnylam's pipeline of investigational RNAi therapeutics
is focused in 3 Strategic Therapeutic Areas (STArs): Genetic
Medicines, with a broad pipeline of RNAi therapeutics for the
treatment of rare diseases; Cardio-Metabolic Disease, with a
pipeline of RNAi therapeutics toward genetically validated,
liver-expressed disease targets for unmet needs in cardiovascular
and metabolic diseases; and Hepatic Infectious Disease, with a
pipeline of RNAi therapeutics that address the major global health
challenges of hepatic infectious diseases. In early 2015, Alnylam
launched its "Alnylam 2020" guidance for the advancement and
commercialization of RNAi therapeutics as a whole new class of
innovative medicines. Specifically, by the end of 2020, Alnylam
expects to achieve a company profile with 3 marketed products, 10
RNAi therapeutic clinical programs - including 4 in late stages of
development - across its 3 STArs. The company's demonstrated
commitment to RNAi therapeutics has enabled it to form major
alliances with leading companies including Ionis, Novartis, Roche,
Takeda, Merck, Monsanto, The Medicines Company, and Sanofi Genzyme.
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, New England Journal of Medicine, and The
Lancet. Founded in 2002, Alnylam maintains headquarters in
Cambridge, Massachusetts. For more information about Alnylam's
pipeline of investigational RNAi therapeutics, 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 views with respect to the potential for RNAi
therapeutics, including fitusiran, its expectations regarding the
timing of clinical studies and the presentation of clinical data,
including for its studies of fitusiran, its expectations regarding
its STAr pipeline growth strategy, its “Alnylam 2020” guidance for
the advancement and commercialization of RNAi therapeutics, and its
plans regarding the pursuit of pre-clinical programs and
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
and future plans may differ materially from those indicated by
these forward-looking statements as a result of various important
risks, uncertainties and other 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 product candidates, the pre-clinical and
clinical results for its product candidates, which may not be
replicated or continue to occur in other subjects or in additional
studies or otherwise support further development of product
candidates for a specified indication or at all, actions or advice
of regulatory agencies, which may affect the design, initiation,
timing, continuation and/or progress of clinical trials or result
in the need for additional pre-clinical and/or clinical testing,
delays, interruptions or failures in the manufacture and supply of
our product candidates, obtaining, maintaining and protecting
intellectual property, Alnylam's ability to enforce its
intellectual property rights against third parties and defend its
patent portfolio against challenges from third parties, obtaining
and maintaining regulatory approval, pricing and reimbursement for
products, progress in establishing a commercial and ex-United
States infrastructure, competition from others using technology
similar to Alnylam's and others developing products for similar
uses, Alnylam's ability to manage its growth and operating
expenses, 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 and distribution of products, the
outcome of litigation, the risk of government investigations, and
unexpected expenditures, as well as those risks more fully
discussed in the "Risk Factors" filed with Alnylam's most recent
Quarterly Report on Form 10-Q 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, except to the
extent required by law, to update any forward-looking
statements.
The scientific information referenced in this news release
relating to fitusiran is preliminary and investigative. Fitusiran
has not been approved by the U.S. Food and Drug Administration,
European Medicines Agency, or any other regulatory authority and no
conclusions can or should be drawn regarding its safety or
effectiveness.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161204005038/en/
Alnylam Pharmaceuticals, Inc.Christine Regan Lindenboom,
617-682-4340(Investors and Media)orJosh Brodsky,
617-551-8276(Investors)
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