– With up to 20 Months of Dosing, Fitusiran
Safety and Tolerability Profile Remains Encouraging –
– Once Monthly, Subcutaneous Fitusiran Achieves
Median Annualized Bleeding Rate (ABR) of One for All Patients and
Zero for Patients with Inhibitors in Exploratory Post-hoc Analysis
–
– New England Journal of Medicine Publishes
Phase 1 Clinical Results with Fitusiran in Patients with Hemophilia
A and B without Inhibitors –
– Alnylam Management to Discuss New Clinical
Data in Webcast Conference Call Monday, July 10, at 11:30 a.m. ET
–
Alnylam Pharmaceuticals,
Inc. (Nasdaq:ALNY), the leading RNAi therapeutics
company and Sanofi Genzyme, the specialty care global business unit
of Sanofi, announced today new positive results from the ongoing
Phase 2 open-label extension (OLE) study with fitusiran in patients
with hemophilia A and B, with or without inhibitors (N=33). These
results were presented today in an oral presentation at the
International Society on Thrombosis and Haemostasis (ISTH) 2017
Congress, being held from July 8 – 13, 2017 in Berlin, Germany.
Fitusiran is an investigational RNAi therapeutic targeting
antithrombin (AT) for the treatment of patients with hemophilia A
and B, that is designed to lower levels of AT with the goal of
promoting sufficient thrombin generation upon activation of the
clotting cascade to restore hemostasis and prevent bleeding. The
companies also announced that Phase 1 clinical trial results
demonstrating an encouraging preliminary safety and tolerability
profile and initial evidence that monthly subcutaneously
administered fitusiran lowered AT levels and increased thrombin
generation in patients with hemophilia A and B without inhibitors
were published online today and will appear in the September 7,
2017, print issue of The New England Journal of
Medicine (NEJM).
The updated clinical results in the fitusiran Phase 2 OLE study
showed that the safety and tolerability profile of fitusiran
remains encouraging, with no thromboembolic events, including
during co-administration of replacement factor or bypassing agents.
The majority of adverse events (AEs) were mild or moderate in
severity, with the most common AEs consisting of transient, mild
injection site reactions (ISRs). In addition, once-monthly
subcutaneous (SC) administration of fitusiran achieved lowering of
AT, increases in thrombin generation, and, in a post-hoc
exploratory analysis, reductions in the median estimated annualized
bleeding rate (ABR) in patients with and without inhibitors. Based
on these results, the companies announced last week the initiation
of the ATLAS Phase 3 program for fitusiran in patients with
hemophilia A and B with or without inhibitors.
“With up to 20 months of dosing in patients, we are encouraged
by the results from our fitusiran clinical studies presented at the
ISTH meeting today, demonstrating what we believe to be promising
support for further clinical development,” said Akin Akinc, Ph.D.,
Alnylam’s Vice President and General Manager, Fitusiran.
“We’re also pleased to have announced initiation of our ATLAS Phase
3 program just last week, where the safety and efficacy of
fitusiran will be evaluated and where we expect initial results in
mid-to-late 2019.”
“We’ve achieved an encouraging safety and tolerability profile
and low median ABRs with a monthly subcutaneous dosing regimen,
highlighting fitusiran’s potential to become a differentiated and
innovative treatment option for patients with hemophilia,” said
Baisong Mei, M.D., Ph.D., Sanofi’s Senior Global Project Head,
Alnylam Portfolio. “We’re now focused on our ATLAS Phase 3 program,
a comprehensive set of studies focused on the unmet needs of
patients with hemophilia A and B with or without inhibitors, which,
if positive, will support global regulatory filings for
fitusiran.”
The ongoing fitusiran Phase 2 OLE study includes patients (N=33)
with hemophilia A (N=27) and hemophilia B (N=6). The study includes
14 patients with inhibitors, including one with hemophilia B.
Fitusiran was administered as a low volume (less than 1 mL),
monthly, subcutaneous, fixed dose of 50 mg (N=13) or 80 mg (N=20).
All results are as of a June 15, 2017 data transfer date.
Patients were treated for up to 20 months in the Phase 2 OLE,
with a median of 11 months on study. The majority of AEs were mild
or moderate in severity, with the most common non-laboratory AEs
consisting of transient, mild ISRs (18 percent of patients). There
was one discontinuation due to an AE, an asymptomatic alanine
aminotransferase (ALT) elevation in a patient with chronic
hepatitis C virus (HCV) infection. Serious adverse events (SAEs)
considered possibly related to drug were reported in two patients:
asymptomatic ALT elevation in one patient with chronic HCV
infection, as noted above, and seizure with confusion in one
patient with a prior history of seizure disorder. Asymptomatic ALT
increases greater than 3x the upper limit of normal (ULN), without
concurrent elevations in bilirubin greater than 2x ULN, were
observed in 11 patients, all of whom were hepatitis C antibody
positive; at current follow-up, all ALT elevations are resolved
(N=10) or resolving (N=1). No thromboembolic events, laboratory
evidence for pathological clot formation, or instances of anti-drug
antibody (ADA) formation were reported.
Regarding clinical activity results, treatment with fitusiran
resulted in approximately 80 percent lowering of AT with
corresponding increases in thrombin generation. Increases in
thrombin generation remained within the lower end of the range of
values observed in normal healthy volunteers. In an exploratory
post-hoc analysis of bleeding events, a median ABR of one
(interquartile range [IQR]: 0-3) was achieved for all patients
(N=33), and a median ABR of zero (IQR: 0-3) was achieved for the
subset of patients with inhibitors (N=14), corresponding favorably
to pre-study median ABR values of 20 (IQR: 4-36) in all patients
and 38 (IQR: 20-48) in inhibitor patients. There was a high
proportion of patients (16 of 33; 48 percent) who remained
bleed-free in the observation period, and most patients (22 of 33;
67 percent) experienced zero spontaneous bleeds. All breakthrough
bleed events were successfully managed with replacement factor
(recombinant factor VIII or recombinant factor IX) or bypassing
agents (recombinant factor VIIa or activated prothrombin complex
concentrate).
As noted above, the companies also announced today that a paper
titled, “Targeting of Antithrombin in Hemophilia A or B with RNAi
Therapy,” was published online today in The New England Journal of
Medicine. Alnylam and its collaborators, including lead author and
principal study investigator John Pasi, M.D., Ph.D., Professor of
Haemostasis and Thrombosis, Clinical Director of Haemophilia at The
Royal London Hospital Barts Health NHS Trust, and Barts and the
London School of Medicine and Dentistry, London, UK, provided
results from Parts A-C of the Phase 1 multicenter, international,
open-label, single- and multiple-ascending dose escalation study in
healthy volunteers and patients with hemophilia A and B without
inhibitors. This is the first publication of safety, tolerability
and initial clinical activity data for fitusiran in patients with
hemophilia A and B.
“Current hemophilia management is based on factor replacement
therapies that require frequent intravenous infusions to maintain
adequate factor trough levels. Significant unmet need remains for
additional therapeutic agents,” said John Pasi. “The results of our
Phase 1 clinical study published in The New England Journal of
Medicine support the growing body of evidence to continue the
clinical development program for fitusiran.”
To view the fitusiran clinical results described in this press
release, please visit www.alnylam.com/capella.
Conference Call Details
Management will discuss these results via conference call
on Monday, July 10, 2017 at 11:30 a.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 50998303. A replay of the
call will be available beginning at 2:30 p.m.
ET on July 10, 2017. To access the replay, please dial
855-859-2056 (domestic) or 404-537-3406 (international), and refer
to conference ID 50998303.
About Hemophilia
Hemophilia is a hereditary bleeding disorder characterized by an
underlying defect in the ability to generate adequate levels of
thrombin needed for effective clotting, thereby resulting in
recurrent bleeds into joints, muscles, and major internal organs.
There are approximately 200,000 persons diagnosed worldwide with
hemophilia A and hemophilia B.
Standard treatment for people with hemophilia currently involves
replacement of the deficient clotting factor either as prophylaxis
or “on-demand” therapy which can lead to a temporary restoration of
thrombin generation capacity. However, as many as one third of
people with severe hemophilia A will develop a neutralizing
antibody to their replacement factor – a very serious complication;
individuals with these ‘inhibitors’ become refractory to standard
replacement factor therapy.
About Fitusiran
Fitusiran is an investigational, once-monthly, subcutaneously
administered RNAi therapeutic targeting antithrombin (AT) for the
treatment of hemophilia A and B, with and without inhibitors.
Fitusiran also has the potential to be used for rare bleeding
disorders. Fitusiran is designed to lower levels of AT with the
goal of promoting sufficient thrombin generation to restore
hemostasis and prevent bleeding. Fitusiran utilizes Alnylam's
ESC-GalNAc conjugate technology, which enables subcutaneous dosing
with increased potency and durability. The clinical significance of
this technology is under investigation.
The safety and efficacy of fitusiran have not been evaluated by
the U.S. Food and Drug Administration or any other health
authority.
Alnylam - Sanofi Genzyme Alliance
In January 2014, Alnylam and Sanofi Genzyme, the specialty care
global business unit of Sanofi, formed an alliance to accelerate
the advancement of RNAi therapeutics as a potential new class of
innovative medicines for patients around the world with rare
genetic diseases. The alliance enables Sanofi Genzyme to expand its
rare disease pipeline with Alnylam’s novel RNAi technology and
provides access to Alnylam’s R&D engine, while Alnylam benefits
from Sanofi Genzyme’s proven global capabilities to advance
late-stage development and, upon commercialization, accelerate
market access for these promising genetic medicine products.
In November 2016, Sanofi Genzyme elected to co-develop (through
Sanofi R&D) and co-commercialize fitusiran in the United
States, Canada and Western Europe, in addition to commercializing
fitusiran in its rest of world territories.
About RNAi
RNAi (RNA interference) is a revolution in biology, representing
a breakthrough in understanding protein synthesis 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, with the goal of preventing
disease-causing proteins from being made.
About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is leading the translation of RNA
interference (RNAi) into a whole new class of innovative medicines
with the potential to transform the lives of patients who have
limited or inadequate treatment options. Based on Nobel
Prize-winning science, RNAi therapeutics represent a powerful,
clinically validated approach for the treatment of a wide range of
debilitating diseases. Founded in 2002, Alnylam is delivering on a
bold vision to turn scientific possibility into reality, with a
robust discovery platform and deep pipeline of investigational
medicines, including three product candidates that are in
late-stage development or will be in 2017. Looking forward, Alnylam
will continue to execute on its "Alnylam 2020" strategy of building
a multi-product, commercial-stage biopharmaceutical company with a
sustainable pipeline of RNAi-based medicines. For more information
about our people, science and pipeline, please
visit www.alnylam.com and engage with us on Twitter at
@Alnylam.
About Sanofi
Sanofi, a global healthcare leader, discovers, develops and
distributes therapeutic solutions focused on patients' needs.
Sanofi is organized into five global business units: Diabetes and
Cardiovascular, General Medicines and Emerging Markets, Sanofi
Genzyme, Sanofi Pasteur and Consumer Healthcare. Sanofi is listed
in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Sanofi Genzyme focuses on developing specialty treatments for
debilitating diseases that are often difficult to diagnose and
treat, providing hope to patients and their families. Learn more at
www.sanofigenzyme.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 the potential for fitusiran for the
treatment of patients with hemophilia A and B, with or without
inhibitors, conduct of its ATLAS Phase 3 program for fitusiran, and
its expectations regarding its "Alnylam 2020" guidance for the
advancement 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 its 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.
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 the safety or effectiveness of fitusiran.
Sanofi Forward-Looking Statements
This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995, as
amended. Forward-looking statements are statements that are not
historical facts. These statements include projections and
estimates and their underlying assumptions, statements regarding
plans, objectives, intentions and expectations with respect to
future financial results, events, operations, services, product
development and potential, and statements regarding future
performance. Forward-looking statements are generally identified by
the words “expects”, “anticipates”, “believes”, “intends”,
“estimates”, “plans” and similar expressions. Although Sanofi’s
management believes that the expectations reflected in such
forward-looking statements are reasonable, investors are cautioned
that forward-looking information and statements are subject to
various risks and uncertainties, many of which are difficult to
predict and generally beyond the control of Sanofi, that could
cause actual results and developments to differ materially from
those expressed in, or implied or projected by, the forward-looking
information and statements. These risks and uncertainties include
among other things, the uncertainties inherent in research and
development, future clinical data and analysis, including post
marketing, decisions by regulatory authorities, such as the FDA or
the EMA, regarding whether and when to approve any drug, device or
biological application that may be filed for any such product
candidates as well as their decisions regarding labelling and other
matters that could affect the availability or commercial potential
of such product candidates, the absence of guarantee that the
product candidates if approved will be commercially successful, the
future approval and commercial success of therapeutic alternatives,
Sanofi’s ability to benefit from external growth opportunities
and/or obtain regulatory clearances, risks associated with
intellectual property and any related pending or future litigation
and the ultimate outcome of such litigation, trends in exchange
rates and prevailing interest rates, volatile economic conditions,
the impact of cost containment initiatives and subsequent changes
thereto, the average number of shares outstanding as well as those
discussed or identified in the public filings with the SEC and the
AMF made by Sanofi, including those listed under “Risk Factors” and
“Cautionary Statement Regarding Forward-Looking Statements” in
Sanofi’s annual report on Form 20-F for the year ended December 31,
2016. Other than as required by applicable law, Sanofi does not
undertake any obligation to update or revise any forward-looking
information or statements.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170710005395/en/
Alnylam Pharmaceuticals, Inc.Investors and MediaChristine
Regan Lindenboom, 617-682-4340orInvestorsJosh Brodsky,
617-551-8276orSanofiMedia RelationsAshleigh Koss,
908-981-8745Mobile: 908-205-2572Ashleigh.koss@sanofi.comorInvestor
RelationsGeorge Grofik, +33 (0)1 53 77 45
45ir@sanofi.comorSanofi GenzymeCommunicationsLisa Clemence,
617-768-6699Lisa.clemence@sanofi.com
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Apr 2024 to May 2024
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From May 2023 to May 2024