− GIVLAARI Approved for the Treatment of Adults
with Acute Hepatic Porphyria (AHP) Based on ENVISION Phase 3 Study
Results Showing Significant Reduction in the Rate of Porphyria
Attacks in Patients with AHP –
− FDA Approval Received in Less Than Four
Months after New Drug Application (NDA) Filing Acceptance –
− GIVLAARI Becomes Second RNAi Therapeutic from
Alnylam Approved by FDA in Last 16 Months and First-Ever Approval
for a GalNAc-Conjugate RNA Therapeutic, a Landmark in Advancement
of Precision Genetic Medicines –
− Alnylam to Host Conference Call Today at 2:15
p.m. ET –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today that the U.S. Food and Drug
Administration (FDA) approved GIVLAARI™ (givosiran) injection for
subcutaneous use for the treatment of adults with acute hepatic
porphyria (AHP). AHP is 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. Long-term
complications of AHP can include chronic neuropathic pain,
hypertension, chronic kidney disease and liver disease. GIVLAARI
was shown to significantly reduce the rate of porphyria attacks
that required hospitalizations, urgent healthcare visits or IV
hemin administration at home.
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20191120005849/en/
GIVLAARI™ (givosiran) packaging and
product vial (Photo: Business Wire)
“We believe the approval of GIVLAARI represents a landmark event
for the advancement of precision genetic medicines, providing new
hope for patients and their caregivers living with the debilitating
manifestations of AHP and unpredictable nature of AHP attacks, as
well as for the doctors who diagnose and treat these patients. We
are grateful to the investigators, patients and families who have
helped make this new treatment option a reality for the AHP
community. We also commend the FDA for recognizing the immense
medical need and granting this approval so quickly,” said John
Maraganore, Ph.D., Chief Executive Officer of Alnylam. “GIVLAARI
now becomes our second RNAi therapeutic to be approved in the last
16 months, and the world’s first-ever GalNAc-conjugate RNA
therapeutic to be approved, representing a watershed moment for a
technology uniquely pioneered by Alnylam scientists. We believe
today’s news reinforces the promise and potential of RNAi
therapeutics as a whole new class of medicines and brings us one
important step closer to fulfilling our Alnylam 2020 goals of
building a multi-product, global commercial company with a deep
clinical pipeline to drive growth and an organic product engine to
fuel sustainable innovation.”
The FDA approval of GIVLAARI was received in less than four
months after acceptance of the NDA, and was based on positive
results from the ENVISION Phase 3 study, a randomized,
double-blind, placebo-controlled, multinational study of 94
patients with AHP, at 36 study sites in 18 countries – the largest
ever interventional study conducted in AHP. In ENVISION, AHP
patients on GIVLAARI experienced 70% (95% CI: 60%, 80%) fewer
porphyria attacks compared to placebo. GIVLAARI also resulted in a
similar reduction in intravenous hemin use, as well as reductions
in urinary aminolevulinic acid (ALA), and urinary porphobilinogen
(PBG).
In the pivotal ENVISION study, the most common adverse reactions
(reported in at least 20% of patients) with GIVLAARI were nausea
(27%) and injection site reactions (25%). Other adverse reactions
seen in patients treated with GIVLAARI (occurring over 5% more
frequently than placebo) include rash, serum creatinine increase,
transaminase elevations and fatigue. As previously reported, one
patient in the GIVLAARI clinical development program experienced an
anaphylactic reaction which resolved with medical management.
“Adults with AHP now have a new treatment option that has
demonstrated the ability to reduce the frequency of porphyria
attacks by specifically addressing factors associated with attacks
and other disease manifestations of AHP,” said Manisha Balwanii,
M.D., M.S, Associate Professor of the Department of Genetics and
Genomic Sciences and Department of Medicine at the Icahn School of
Medicine at Mount Sinai and principal investigator of the ENVISION
study. “With the approval of GIVLAARI, and based on the efficacy
data from the ENVISION study, I hope to see my patients and those
across the country be able to live more normal lives with fewer
porphyria attacks.”
“The FDA approval of GIVLAARI is an important milestone for our
community, as we now have a new treatment option for adults living
with acute hepatic porphyria,” said Kristen Wheeden, Executive
Director, American Porphyria Foundation. “AHP can have a profound
impact on the lives of patients and their families. Porphyria
attacks are associated with severe, incapacitating pain, often
requiring hospitalization for management. In addition, many
patients struggle on a daily basis with chronic symptoms related to
their disease. The approval of GIVLAARI is exciting for our
community.”
Alnylam is committed to helping people access the medicines they
are prescribed and will be offering comprehensive support services
for people prescribed GIVLAARI through Alnylam Assist®. Visit
AlnylamAssist.com for more information or call 1-833-256-2748.
GIVLAARI is expected to be available for shipment to healthcare
providers in the U.S. by year-end. HCPs can initiate the process
now by visiting www.AlnylamAssist.com and completing and submitting
a Start Form.
In August, Alnylam announced a U.S. gastrointestinal (GI)
disease education and promotional agreement for GIVLAARI with
Ironwood Pharmaceuticals, Inc., a GI healthcare company. Under the
agreement, Alnylam will leverage Ironwood’s leading capabilities in
GI to help raise awareness of AHP among gastroenterologists and
other healthcare practitioners in the U.S. Ironwood will also
participate in GIVLAARI promotional efforts, augmenting Alnylam’s
broader commercialization activities.
GIVLAARI was reviewed by the FDA under Priority Review and had
previously been granted Breakthrough Therapy and Orphan Drug
Designations in the U.S. GIVLAARI is currently being reviewed under
accelerated assessment by the European Medicines Agency (EMA) for
the treatment of patients with AHP, after receiving Priority
Medicines (PRIME) Designation and Orphan Drug Designation from the
EMA.
Visit GIVLAARI.com for more information, including full
Prescribing Information.
Conference Call Information Alnylam management will
discuss the FDA approval via conference call today, November 20,
2019 at 2:15 p.m. ET. A webcast presentation will also be available
on the Investors page of the Company’s website, www.alnylam.com. To
access the call, please dial 800-239-9838 (domestic) or
+1-323-794-2551 (international) five minutes prior to the start
time and refer to conference ID 6976021. A replay of the call will
be available beginning at 5:00 pm ET on the day of the call. To
access the replay, please dial 888-203-1112 (domestic) or
+1-719-457-0820 (international) and refer to conference ID
6976021.
IMPORTANT SAFETY INFORMATION
Contraindications GIVLAARI is contraindicated in patients
with known severe hypersensitivity to givosiran. Reactions have
included anaphylaxis.
Anaphylactic Reaction Anaphylaxis has occurred with
GIVLAARI treatment (<1% of patients in clinical trials). Ensure
that medical support is available to appropriately manage
anaphylactic reactions when administering GIVLAARI. Monitor for
signs and symptoms of anaphylaxis. If anaphylaxis occurs,
immediately discontinue administration of GIVLAARI and institute
appropriate medical treatment.
Hepatic Toxicity Transaminase elevations (ALT) of at
least 3 times the upper limit of normal (ULN) were observed in 15%
of patients receiving GIVLAARI in the placebo-controlled trial.
Transaminase elevations primarily occurred between 3 to 5 months
following initiation of treatment.
Measure liver function tests prior to initiating treatment with
GIVLAARI, repeat every month during the first 6 months of
treatment, and as clinically indicated thereafter. Interrupt or
discontinue treatment with GIVLAARI for severe or clinically
significant transaminase elevations. In patients who have dose
interruption and subsequent improvement, reduce the dose to 1.25
mg/kg once monthly. The dose may be increased to the recommended
dose of 2.5 mg/kg once monthly if there is no recurrence of severe
or clinically significant transaminase elevations at the 1.25 mg/kg
dose.
Renal Toxicity Increases in serum creatinine levels and
decreases in estimated glomerular filtration rate (eGFR) have been
reported during treatment with GIVLAARI. In the placebo-controlled
study, 15% of patients receiving GIVLAARI experienced a
renally-related adverse reaction. The median increase in creatinine
at Month 3 was 0.07 mg/dL. Monitor renal function during treatment
with GIVLAARI as clinically indicated.
Injection Site Reactions Injection site reactions were
reported in 25% of patients receiving GIVLAARI in the
placebo-controlled trial. Symptoms included erythema, pain,
pruritus, rash, discoloration, or swelling around the injection
site. One (2%) patient experienced a single, transient, recall
reaction of erythema at a prior injection site with a subsequent
dose administration.
Drug Interactions Concomitant use of GIVLAARI increases
the concentration of CYP1A2 or CYP2D6 substrates, which may
increase adverse reactions of these substrates. Avoid concomitant
use of GIVLAARI with CYP1A2 or CYP2D6 substrates for which minimal
concentration changes may lead to serious or life-threatening
toxicities. If concomitant use is unavoidable, decrease the CYP1A2
or CYP2D6 substrate dosage in accordance with approved product
labeling.
Adverse Reactions The most common adverse reactions that
occurred in patients receiving GIVLAARI were nausea (27%) and
injection site reactions (25%).
For additional information about GIVLAARI, please see full
Prescribing Information.
About GIVLAARI™ (givosiran)
GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid
synthase 1 (ALAS1) for the treatment of adults with acute hepatic
porphyria (AHP). In the pivotal study, GIVLAARI was shown to
significantly reduce the rate of porphyria attacks that required
hospitalizations, urgent healthcare visits or IV 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. For more information about GIVLAARI, visit GIVLAARI.com.
About AHP
Acute hepatic porphyria (AHP) refers to a family of ultra-rare,
genetic diseases characterized by potentially life-threatening
attacks and, for some patients, chronic manifestations that
negatively impact daily functioning and quality of life. AHP is
comprised of four types: 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 deficiency in one of the enzymes
of the heme biosynthesis pathway in the liver. 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. The nonspecific nature of AHP signs and symptoms can often
lead to misdiagnoses of other more common conditions such as viral
gastroenteritis, irritable bowel syndrome (IBS), addiction
withdrawal and appendicitis. Consequently, patients with AHP can
wait up to 15 years for a confirmed diagnosis. 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, and Switzerland, and GIVLAARI™
(givosiran), approved in the U.S. 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 employs over 1,200 people
worldwide and is headquartered in Cambridge, MA. For more
information about our people, science and pipeline, please visit
www.alnylam.com and engage with us on Twitter at @Alnylam or on
LinkedIn.
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
concerning when GIVLAARI will be available for shipment to
healthcare providers in the U.S., its plan to offer comprehensive
support services for people prescribed GIVLAARI through Alnylam
Assist®, its plans to leverage Ironwood’s capabilities in GI to
help raise awareness of AHP among U.S. healthcare practitioners and
assist in GIVLAARI promotional efforts, expectations regarding the
review of GIVLAARI’s MAA under accelerated assessment by the EMA
for the treatment of patients with AHP, 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, 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, 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.
i Dr. Manisha Balwani (the Principal Investigator in this study)
receives financial compensation as a consultant for Alnylam
Pharmaceuticals (the study sponsor). In addition, Mount Sinai
faculty are named Co-Inventors with Alnylam on a patent related to
the development of givosiran, the study drug. The Icahn School of
Medicine at Mount Sinai receives payments related to this patent
from Alnylam, and a portion of these payments are also distributed
to faculty and other co-inventors.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191120005849/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media)
617-682-4340 Joshua Brodsky (Investors) 617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Mar 2024 to Apr 2024
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Apr 2023 to Apr 2024