− Patients Receiving Givosiran in Pivotal Phase
3 ENVISION Study had a 74 Percent Mean Reduction in Annualized Rate
of Composite Porphyria Attacks Compared to Placebo –
Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading RNAi
therapeutics company, today announced the submission of a Marketing
Authorization Application (MAA) to the European Medicines Agency
(EMA) for givosiran, an investigational RNAi therapeutic targeting
aminolevulinic acid synthase 1 (ALAS1) in development for the
treatment of acute hepatic porphyria (AHP).
Givosiran has been granted Priority Medicines (PRIME)
Designation by the EMA as well as Orphan Designation in the
European Union. Givosiran has also been granted an accelerated
assessment by the EMA which is awarded to medicines deemed to be of
major public health interest and therapeutic innovation, and the
award is designed to bring new treatments to patients more quickly.
Accelerated assessment potentially provides a reduced review
timeline from 210 to 150 days once the MAA is filed and
validated.
“Patients living with acute hepatic porphyria often suffer from
chronic pain and unbearable, debilitating attacks, with limited
treatment options available. Today’s announcement takes us a step
closer to providing a new therapeutic option to patients in
Europe,” said Akin Akinc, Ph.D., Vice President and General
Manager, Givosiran Program at Alnylam. “We believe givosiran has
the potential to be a transformative medicine for patients with
acute hepatic porphyria and we look forward to working closely with
the EMA to bring this innovative new medicine to patients and their
families in Europe.”
Findings from the pivotal ENVISION Phase 3 study are included as
part of the application and were presented in April 2019 at the
54th Annual International Liver Congress™ of the European
Association for the Study of the Liver (EASL). In the ENVISION
study, patients receiving givosiran had a 74 percent mean reduction
in the annualized rate of composite porphyria attacks compared to
placebo, with an acceptable overall safety and tolerability
profile.
Givosiran has also previously received Breakthrough Therapy
Designation from the U.S. Food and Drug Administration (FDA) and
Orphan Drug Designation in the U.S. for acute hepatic porphyria. A
New Drug Application for givosiran has been submitted to the
FDA.
About Givosiran Givosiran is an investigational,
subcutaneously administered RNAi therapeutic targeting
aminolevulinic acid synthase 1 (ALAS1) in development for the
treatment of acute hepatic porphyria (AHP). Monthly administration
of givosiran has the potential to significantly lower induced liver
ALAS1 levels in a sustained manner and thereby decrease neurotoxic
heme intermediates, aminolevulinic acid (ALA) and porphobilinogen
(PBG), towards normal levels. By reducing accumulation of these
intermediates, givosiran has the potential to prevent or reduce the
occurrence of severe and life-threatening attacks, control chronic
symptoms, and decrease the burden of the disease. Givosiran
utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC) -GalNAc
conjugate technology, which enables subcutaneous dosing with
increased potency and durability and a wide therapeutic index. The
safety and efficacy of givosiran were evaluated in the ENVISION
Phase 3 trial with positive results; these results have not been
evaluated by the FDA, the EMA or any other health authority.
About ENVISION Phase 3 Study The ENVISION Phase 3 trial
was a randomized, double-blind, placebo-controlled, global,
multicenter study to evaluate the efficacy and safety of givosiran
in patients with a documented diagnosis of acute hepatic porphyria
(AHP). The primary endpoint was reduction relative to placebo in
the annualized rate of composite porphyria attacks, defined as
those requiring hospitalization, urgent healthcare visit, or hemin
administration at home, in patients with acute intermittent
porphyria (AIP, the most common subtype of AHP) over six months.
Key secondary and exploratory endpoints evaluated reductions in
neurotoxic heme intermediates, aminolevulinic acid (ALA) and
porphobilinogen (PBG), usage of hemin, symptoms of AHP, such as
pain, nausea, and fatigue, as well as impact on quality of life.
The trial enrolled 94 patients with AHP, at 36 study sites in 18
countries around the world and is the largest ever interventional
study conducted in AHP. Patients were randomized 1:1 to givosiran
or placebo, with givosiran administered subcutaneously at 2.5 mg/kg
monthly. Upon completion of dosing in the double-blind period, all
eligible patients (99 percent) enrolled in the ENVISION open-label
extension (OLE) to receive givosiran on an ongoing basis.
About Acute Hepatic Porphyria Acute hepatic porphyria
(AHP) refers to a family of rare, genetic diseases characterized by
potentially life-threatening attacks and for some patients chronic
debilitating symptoms that negatively impact daily functioning and
quality of life. AHP is comprised of four subtypes, each resulting
from a genetic defect leading to deficiency in one of the enzymes
of the heme biosynthesis pathway in the liver: acute intermittent
porphyria (AIP), hereditary coproporphyria (HCP), variegate
porphyria (VP), and ALAD-deficiency porphyria (ADP). These defects
cause the accumulation of neurotoxic heme intermediates
aminolevulinic acid (ALA) and porphobilinogen (PBG), with ALA
believed to be the primary neurotoxic intermediate responsible for
causing both attacks and ongoing symptoms between attacks. Common
symptoms of AHP include severe, diffuse abdominal pain, weakness,
nausea, and fatigue. The nonspecific nature of AHP signs and
symptoms can often lead to misdiagnoses of other more common
conditions such as irritable bowel syndrome, appendicitis,
fibromyalgia, and endometriosis, and consequently, patients
afflicted by AHP often remain without a proper diagnosis for up to
15 years. In addition, long-term complications of AHP and its
treatment can include chronic neuropathic pain, hypertension,
chronic kidney disease and liver disease, including iron overload,
fibrosis, cirrhosis and hepatocellular carcinoma. Currently, there
are no treatments approved to prevent debilitating attacks or to
treat the chronic manifestations of the disease.
About RNAi RNAi (RNA interference) is a natural cellular
process of gene silencing that represents one of the most promising
and rapidly advancing frontiers in biology and drug development
today. Its discovery has been heralded as “a major scientific
breakthrough that happens once every decade or so,” and was
recognized with the award of the 2006 Nobel Prize for Physiology or
Medicine. By harnessing the natural biological process of RNAi
occurring in our cells, a new class of medicines, known as RNAi
therapeutics, is now a reality. Small interfering RNA (siRNA), the
molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic
platform, function upstream of today’s medicines by potently
silencing messenger RNA (mRNA) – the genetic precursors – that
encode for disease-causing proteins, thus preventing them from
being made. This is a revolutionary approach with the potential to
transform the care of patients with genetic and other diseases.
About Alnylam Pharmaceuticals Alnylam (Nasdaq:ALNY) is
leading the translation of RNA interference (RNAi) into a new class
of innovative medicines with the potential to transform the lives
of people afflicted with rare genetic, cardio-metabolic, hepatic
infectious, and central nervous system/ocular diseases. Based on
Nobel Prizewinning science, RNAi therapeutics represent a powerful,
clinically validated approach for the treatment of diseases with
high unmet need. ONPATTRO® (patisiran) is the first-ever RNAi
therapeutic approved by the U.S. FDA for the treatment of the
polyneuropathy of hereditary transthyretin-mediated (hATTR)
amyloidosis in adults and by the EMA for the treatment of hATTR
amyloidosis in adults with stage 1 or stage 2 polyneuropathy.
Alnylam has a deep pipeline of investigational medicines, including
five product candidates in Phase 3 studies and one in registration.
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 to address the needs of patients who have limited or
inadequate treatment options. Headquartered in Cambridge, MA,
Alnylam employs over 1,200 people worldwide.
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 treatment benefits of givosiran and
potential for givosiran to impact the lives of patients, the safety
and tolerability profile for givosiran, and 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, successfully launching, marketing and
selling its approved products globally, Alnylam’s ability to
successfully expand the indication for ONPATTRO in the future,
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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190701005257/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media) +1-617-682-4340
Josh Brodsky (Investors) +1-617-551-8276
Fiona McMillan (Media, Europe) +44 1628 244960
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