− GIVLAARI is the First and Only Therapy Proven
to Prevent AHP Attacks, Reduce Chronic Pain and Improve Quality of
Life −
− GIVLAARI Approved Based on ENVISION Phase 3
Study Results Showing a 74% Reduction in the Rate of Porphyria
Attacks −
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today announced that the European Commission
(EC) has granted marketing authorization for GIVLAARI® (givosiran),
an injection for subcutaneous use targeting aminolevulinic acid
synthase 1 (ALAS1) for the treatment of acute hepatic porphyria
(AHP) in adults and adolescents aged 12 years and older. AHP is an
ultra-rare condition in which patients can experience debilitating
attacks of severe abdominal pain, vomiting and seizures, which can
be life-threatening due to the possibility of paralysis and
respiratory arrest during attacks. Many patients also experience
chronic symptoms, including pain, which continue to be present
between attacks.
“Today’s approval of GIVLAARI marks a historic moment for
patients and families living with this devastating genetic disease,
as there are currently no approved medicines in Europe proven to
decrease the frequency of attacks and reduce the chronic pain that
many patients suffer,” said John Maraganore, Ph.D., Chief Executive
Officer of Alnylam. “We are proud to bring GIVLAARI, our second
RNAi medicine to be approved in the last 18 months, to patients in
Europe and we want to thank the patients, families, investigators
and study staff whose support and involvement have made this
achievement possible.”
“The fear of not knowing when an attack will strike, combined
with ongoing symptoms between attacks, affects every aspect of
patients’ lives, limiting their ability to work and maintain a
social life,” said Dr Eliane Sardh, Head of the Porphyria Centre
Sweden, Karolinska University Hospital, Sweden. “In our experience,
life is very different for patients since they have been treated
with givosiran. In addition to a reduction in the number of
porphyria attacks which require hospitalization and urgent
healthcare visits, we have seen improvements in how patients report
their overall health status and quality of life, so this approval
is truly meaningful for patients, their families and the healthcare
professionals who treat them. Some of our patients have been able
to achieve significant personal and professional milestones that
would not have been possible before.”
“We are committed to bringing GIVLAARI to patients in Europe as
rapidly as possible, and plan to build on our experience in the
U.S. by proactively engaging with national authorities in Europe
around a value-based agreement framework which we hope will
accelerate patient and provider access to GIVLAARI,” said Barry
Greene, President, Alnylam. “While every country has its own
process for measuring the value of new medicines, we believe this
framework will appeal in many countries as it combines payment
based on performance with additional financial mechanisms to ensure
the long-term financial sustainability of the treatment of all AHP
patients in line with the authorized indication of GIVLAARI.”
GIVLAARI (givosiran) was granted Priority Medicines (PRIME)
Designation by the European Medicines Agency (EMA) as well as
Orphan Designation in the European Union. GIVLAARI was also granted
an accelerated assessment, 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. This EC approval follows the recent approval of GIVLAARI
by the U.S. Food and Drug Administration in November 2019.
Givosiran is also awaiting approval in Brazil where it is under
priority review.
About ENVISION Phase 3 Study The marketing authorization
was based on positive data from the ENVISION Phase 3 trial, 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 intravenous
hemin administration at home, in patients with acute intermittent
porphyria (AIP, the most common subtype of AHP) over six months.
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%) enrolled in the ENVISION open-label
extension (OLE) to receive givosiran on an ongoing basis.
- In the study, givosiran demonstrated a 74% reduction in the
annualized composite rate of porphyria attacks in AIP patients
relative to placebo.
- 50% of patients on givosiran were attack-free during the
six-month treatment period as compared to 16.3% of placebo-treated
patients.
- Patient-reported daily worst pain was significantly improved
with givosiran vs placebo in patients with AIP (p<0.05).
- Givosiran reduced use of hemin, as well as urinary
aminolevulinic acid (ALA), and urinary porphobilinogen (PBG).
- A greater proportion of patients on givosiran reported
improvements in their overall health, pain, daily functioning,
compared to placebo.
The most frequently occurring adverse reactions reported in
patients treated with givosiran are injection site reactions (36%),
nausea (32.4%) and fatigue (22.5%). Other adverse reactions seen in
givosiran treated patients (occurring ≥10% more frequently than
placebo) include transaminase elevations, rash and glomerular
filtration rate decrease.
About GIVLAARI® (givosiran) GIVLAARI is an RNAi
therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for
the treatment of adults and adolescents with acute hepatic
porphyria (AHP). In the pivotal study, givosiran was shown to
significantly reduce the rate of porphyria attacks that required
hospitalizations, urgent healthcare visits or intravenous hemin
administration at home compared to placebo. GIVLAARI is Alnylam’s
first commercially available therapeutic based on its Enhanced
Stabilization Chemistry ESC-GalNAc conjugate technology to increase
potency and durability. GIVLAARI is administered via subcutaneous
injection once monthly at a dose based on actual body weight and
should be administered by a healthcare professional. GIVLAARI works
by specifically reducing elevated levels of aminolevulinic acid
synthase 1 (ALAS1) messenger RNA (mRNA), leading to reduction of
toxins associated with attacks and other disease manifestations of
AHP.
About Acute Hepatic Porphyria Acute hepatic porphyria
(AHP) refers to a family of ultra-rare, genetic diseases
characterized by debilitating, potentially life-threatening attacks
and, for some patients, chronic manifestations that negatively
impact daily functioning and quality of life. AHP is comprised of
four subtypes: acute intermittent porphyria (AIP), hereditary
coproporphyria (HCP), variegate porphyria (VP), and ALA
dehydratase-deficiency porphyria (ADP). Each type of AHP results
from a genetic defect leading to a lack of certain enzymes needed
to produce heme in the liver, which leads to an accumulation of
porphyrins in the body to toxic amounts. AHP disproportionately
impacts women of working and childbearing age, and symptoms of the
disease vary widely. Severe, unexplained abdominal pain is the most
common symptom, which can be accompanied by limb, back, or chest
pain, nausea, vomiting, confusion, anxiety, seizures, weak limbs,
constipation, diarrhea, or dark or reddish urine. AHP is
life-threatening due to the possibility of paralysis and
respiratory arrest during attacks. The nonspecific nature of AHP
signs and symptoms can often lead to misdiagnoses of other more
common conditions such as gynecological disorders, viral
gastroenteritis, irritable bowel syndrome (IBS), and appendicitis.
Consequently, on a global perspective, patients with AHP can wait
up to 15 years for a confirmed diagnosis, with the risk of
addiction problems. In addition, long-term complications and
comorbidities of AHP can include hypertension, chronic kidney
disease or liver disease, including hepatocellular carcinoma.
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 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
people afflicted with rare genetic, cardio-metabolic, hepatic
infectious, and central nervous system (CNS)/ocular diseases. Based
on Nobel Prize-winning science, RNAi therapeutics represent a
powerful, clinically validated approach for the treatment of a wide
range of severe and debilitating diseases. Founded in 2002, Alnylam
is delivering on a bold vision to turn scientific possibility into
reality, with a robust RNAi therapeutics platform. Alnylam’s
commercial RNAi therapeutic products are ONPATTRO® (patisiran),
approved in the U.S., EU, Canada, Japan, Brazil and Switzerland,
and GIVLAARI® (givosiran), approved in the U.S and the EU. Alnylam
has a deep pipeline of investigational medicines, including five
product candidates that are in late-stage development. Alnylam is
executing 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.
Alnylam is headquartered in Cambridge, MA.
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 approval of GIVLAARI® (givosiran) injection for
subcutaneous use, and the implications of such approval for
patients and their caregivers, the results of the ENVISION Phase 3
clinical trial for givosiran, expectations regarding the review of
GIVLAARI’s marketing authorization application under accelerated
assessment by the EMA for the treatment of patients with AHP, and
expectations regarding Alnylam’s “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, including GIVLAARI,
progress in establishing a commercial and ex-United States
infrastructure, successfully launching, marketing and selling its
approved products globally, including GIVLAARI, 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 and achieve a
self-sustainable financial profile in the future, 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, including Regeneron, for
development, manufacture and distribution of products, and
Ironwood, for assistance with the education about and promotion of
GIVLAARI in the United States, 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 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, except to the
extent required by law, to update any forward-looking
statements.
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version on businesswire.com: https://www.businesswire.com/news/home/20200303005205/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
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