– Once-Monthly, Subcutaneous Fitusiran Achieves
Median Annualized Bleeding Rate (ABR) of Zero in this Hemophilia
Patient Segment with Highest Unmet Need –
– Fitusiran Generally Well Tolerated with No
Thromboembolic Events, Including with Co-Administration of
Bypassing Agents –
– Alnylam On Track to Initiate Phase 3 Program
in Early 2017 –
– Management to Discuss New Clinical Data in
Webcast Conference Call Tomorrow, Sunday, December 4, at 1:00 p.m.
ET –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today announced positive interim results from
Part D of its ongoing Phase 1 study with fitusiran, an
investigational RNAi therapeutic, in patients with hemophilia with
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 lowering of AT and increases
in thrombin generation, resulting in a median estimated annualized
bleeding rate (ABR) of zero in patients with hemophilia A or B with
inhibitors (N=16). In addition, fitusiran was generally well
tolerated through the data cut-off date, October 6, 2016, with no
thromboembolic events, including in circumstances when bypassing
agents were administered to treat breakthrough bleeding events.
Additional data on longer-term administration of fitusiran in
patients without inhibitors will be presented in a separate poster
presentation at ASH tomorrow, Sunday, December 4.
“As many as one-third of severe hemophilia A patients will
develop inhibitors, one of the most serious treatment-related
complications of hemophilia. We believe that achievement of a
median ABR of zero in this study population is very encouraging, as
the prophylactic treatment options for patients with inhibitors are
limited and may be suboptimal for many patients,” said Akin Akinc,
Ph.D., Vice President and General Manager, Fitusiran. “We look
forward to continuing to study fitusiran in hemophilia patients
with and without inhibitors, and plan to initiate our Phase 3
program in early 2017.”
New results as of an October 6, 2016 data cut-off date were
presented from Part D of the ongoing fitusiran Phase 1 study, which
included patients with hemophilia A or B with inhibitors who were
enrolled in two separate dose cohorts of 50 mg, once-monthly (N=6)
or 80 mg, once-monthly (N=10). Treatment with fitusiran resulted in
potent and dose-dependent lowering of AT and increases in thrombin
generation. In an exploratory analysis of bleeding events, a median
ABR of zero was achieved for patients in combined dose cohorts in
the observation period, compared to the pre-study median ABR of 31.
The majority of patients treated in both cohorts (9 of 16; 56
percent) were bleed-free and most patients (11 of 16; 69 percent)
experienced zero spontaneous bleeds. In the 80 mg cohort, 70
percent (7 out of 10) of patients were bleed-free and 90 percent (9
out of 10) of patients experienced zero spontaneous bleeds.
Fitusiran was generally well tolerated in the study. All adverse
events (AEs) were mild or moderate in severity, with the most
common AEs consisting of mild injection site reactions (ISRs) in 8
out of 16 patients (50 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, all of whom have medical history of hepatitis C infection
(HCV). Non-clinically significant increases in D-dimer were
observed in some patients; none were associated with laboratory
signs of pathologic clot formation. There were no drug-related
serious adverse events (SAEs), no discontinuations due to AEs, and
no thromboembolic events through the data cut-off date. All
breakthrough bleed events were successfully managed with bypassing
agents (recombinant factor VIIa and/or activated prothrombin
complex concentrate). As of the data cut-off date, seven inhibitor
patients have transitioned to the Phase 2 open-label extension
(OLE) study, and continued dosing with fitusiran for up to seven
months has been generally well tolerated.
To view the fitusiran clinical results described in this press
release, please visit www.alnylam.com/capella.
Conference Call InformationAlnylam management will
discuss these clinical data in a webcast conference call
tomorrow, 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 Phase 1 StudyThe ongoing Phase 1 trial of
fitusiran is being conducted in the United States, Bulgaria,
Russia, Switzerland, and the U.K. as a single- and multi-dose,
dose-escalation study comprised of four parts. Part A – which is
complete – was a randomized, single-blind, placebo-controlled,
single-dose, dose-escalation study (N=4 per cohort; 3:1
randomization of fitusiran:placebo) in healthy volunteers. This
part of the study was completed after the first dose cohort
received a single subcutaneous dose of fitusiran at 30 mcg/kg. Part
B of the study – which is also complete – was an open-label,
multi-dose, dose-escalation study that enrolled 12 patients with
severe hemophilia A or B. Patients in Part B received three weekly
subcutaneous injections of fitusiran at doses of 15, 45, or 75
mcg/kg. Part C of the study – which has completed dosing – is an
open-label, multi-dose, dose escalation study that enrolled 18
patients with moderate or severe hemophilia A or B without
inhibitors. Twelve patients in Part C received three monthly
subcutaneous doses of fitusiran at doses of 225, 450, 900, or 1800
mcg/kg. In addition, six patients in Part C received three fixed
monthly subcutaneous doses of fitusiran at 80 mg. Part D of the
study is designed to enroll up to 18 patients with inhibitors.
Patients in Part D received 3 fixed monthly subcutaneous doses of
fitusiran at 50 mg or 80 mg. The primary objective of Parts B, C,
and D of the study is to evaluate the safety and tolerability of
multiple doses of subcutaneously administered fitusiran in patients
with hemophilia, with and without inhibitors. Secondary objectives
include assessment of clinical activity as determined by lowering
of circulating AT levels and increase in thrombin generation at
pharmacologic doses of fitusiran. In addition, exploratory analyses
of bleeding are being performed. In the U.K., enrollment has been
aided by the Southern Academic Coagulation Consortium (SACC).
About FitusiranFitusiran 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 AllianceIn 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 RNAiRNAi (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 PharmaceuticalsAlnylam 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 StatementsVarious 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/20161203005046/en/
Alnylam Pharmaceuticals, Inc.Investors and MediaChristine
Regan Lindenboom, 617-682-4340orInvestorsJosh Brodsky,
617-551-8276
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