– First-Ever Study to Have Evaluated the
Safety and Efficacy of an Investigational RNAi Therapeutic in
Infants and Children Under the Age of Six –
– Lumasiran Demonstrated Clinically Significant
Reduction in Urinary Oxalate Levels Relative to Baseline in
Children as Young as Four Months Old –
– Safety and Tolerability Profile Consistent
with That Observed in ILLUMINATE-A Phase 3 Pivotal Study –
– Full Results Planned to be Presented at
the American Society of Nephrology Annual Meeting in October 2020
–
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today positive topline results from
the ILLUMINATE-B pediatric Phase 3 study of lumasiran, an
investigational RNAi therapeutic targeting hydroxyacid oxidase 1
(HAO1) – the gene encoding glycolate oxidase (GO) – in development
for the treatment of primary hyperoxaluria type 1 (PH1).
ILLUMINATE-B is now the seventh Phase 3 study of an RNAi
therapeutic that has yielded positive results, and the first-ever
study evaluating the safety and efficacy of this new class of
medicines in children under the age of six, including infants.
“We are pleased to report these positive topline results that we
believe hold promise for many families impacted by PH1. The safety
and efficacy of lumasiran are consistent with that reported for the
ILLUMINATE-A study in patients six and older, demonstrating that
lumasiran can significantly reduce the hepatic production of
oxalate across all ages, which we believe can thereby address the
underlying pathophysiology of PH1,” said Pritesh J. Gandhi,
PharmD., Vice President and General Manager, Lumasiran Program at
Alnylam. “The current standard of care for young children and
infants diagnosed with PH1 is burdensome, including the frequent
need for gastrostomy tube placement to enable hyperhydration, and,
for those who have progressed to advanced disease, the risks
associated with performing dialysis and, ultimately, organ
transplantation. Thus, we believe, a meaningful reduction in
urinary oxalate levels has the potential to favorably impact
disease progression and management in very young patients. We look
forward to reporting complete data from the ILLUMINATE-B study at
the ASN virtual congress later this fall.”
“The ILLUMINATE-B results signal hope for the many families with
children whose lives are deeply impacted by PH1. This is especially
encouraging given that children as young as a few months old could
benefit from the therapeutic approach that lumasiran offers,
curbing production of oxalate at its source,” said Kim Hollander,
Executive Director of the Oxalosis and Hyperoxaluria Foundation.
“We are grateful to Alnylam for their continued commitment to the
PH1 community and for designing and successfully conducting a study
that addresses a particularly vulnerable group of patients – young
children and babies.”
ILLUMINATE-B Topline Study Results
ILLUMINATE-B (NCT03905694) is a single arm, open-label,
multicenter Phase 3 trial that enrolled 18 patients with PH1 under
the age of six (range: 3-72 months), with an estimated glomerular
filtration rate (eGFR) of greater than 45 mL/min/1.73 m2 or normal
serum creatinine if less than 12 months old, at nine study sites,
in five countries around the world. Lumasiran was administered
according to a weight-based dosing regimen. The primary efficacy
endpoint of the study was the percent change from baseline to Month
6 in spot urinary oxalate:creatinine ratio averaged across Months 3
to 6. At six months, relative to baseline, lumasiran demonstrated a
clinically meaningful reduction in spot urinary oxalate:creatinine
ratio. Reduction of urinary oxalate relative to baseline was
consistent across all three body weight categories (less than 10
kg; 10 kg to less than 20 kg, and 20 kg or higher). Lumasiran
demonstrated positive results across secondary endpoints, including
additional measures of urinary and plasma oxalate. There were no
serious or severe adverse events related to study drug, and the
overall safety and tolerability profile of lumasiran was consistent
with that observed in the ILLUMINATE-A study. Full ILLUMINATE-B
study results will be presented on October 22, 2020 at the ASN
virtual congress.
Lumasiran has received U.S. and EU Orphan Drug Designations,
Breakthrough Therapy and Rare Pediatric Disease Designations from
the U.S. Food and Drug Administration (FDA), and a Priority
Medicines (PRIME) designation from the European Medicines Agency
(EMA). Alnylam has filed a New Drug Application (NDA) for lumasiran
with the U.S. FDA. The FDA has granted a Priority Review for the
NDA and has set an action date of December 3, 2020 under the
Prescription Drug User Fee Act (PDUFA). In addition, the Marketing
Authorisation Application (MAA) for lumasiran has been submitted to
and validated by the EMA and has received Accelerated Assessment
designation.
The Company is also conducting ILLUMINATE-C – a global
single-arm Phase 3 study of lumasiran in PH1 patients of all ages
with advanced renal disease, including patients on dialysis, with
results expected in 2021.
About ILLUMINATE-A Phase 3 Study
ILLUMINATE-A (NCT03681184) is a six-month randomized,
double-blind, placebo-controlled, global, multicenter Phase 3 study
(with a 54-month extension period) to evaluate the efficacy and
safety of lumasiran in 39 patients with a documented diagnosis of
PH1. Patients were randomized 2:1 to receive three monthly doses of
lumasiran or placebo followed by quarterly maintenance doses at 3
mg/kg. The primary endpoint was the percent change in 24-hour
urinary oxalate excretion from baseline to the average of months 3
to 6 in the patients treated with lumasiran as compared to placebo.
Treatment arms were stratified at randomization based upon mean
24-hour urinary oxalate during screening (≤ 1.7 or > 1.7
mmol/24hr/1.73m2). Key secondary and exploratory endpoints were
designed to evaluate additional measures of urinary oxalate, plasma
oxalate, estimated glomerular filtration rate (eGFR),
nephrocalcinosis, renal stone events, safety and tolerability.
About Lumasiran
Lumasiran is an investigational, subcutaneously administered
RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in
development for the treatment of primary hyperoxaluria type 1
(PH1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1
and depleting the GO enzyme, lumasiran inhibits production of
oxalate – the metabolite that directly contributes to the
pathophysiology of PH1. Lumasiran utilizes Alnylam's Enhanced
Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which
enables subcutaneous dosing with increased potency and durability
and a wide therapeutic index. Lumasiran has received both U.S. and
EU Orphan Drug Designations, Breakthrough Therapy Designation from
the U.S. Food and Drug Administration (FDA), and Priority Medicines
(PRIME) designation from the European Medicines Agency (EMA). The
safety and efficacy of lumasiran are under evaluation by the FDA
and EMA.
About Primary Hyperoxaluria Type 1 (PH1)
PH1 is an ultra-rare disease in which excessive oxalate
production results in the deposition of calcium oxalate crystals in
the kidneys and urinary tract and can lead to the formation of
painful and recurrent kidney stones and nephrocalcinosis. Renal
damage is caused by a combination of tubular toxicity from oxalate,
calcium oxalate deposition in the kidneys, and urinary obstruction
by calcium oxalate stones. Compromised kidney function exacerbates
the disease as the excess oxalate can no longer be effectively
excreted, resulting in subsequent accumulation and crystallization
in bones, eyes, skin, and heart, leading to severe illness and
death. Current treatment options are very limited and include
frequent renal dialysis or combined organ transplantation of liver
and kidney, a procedure with high morbidity that is limited due to
organ availability. Although a small minority of patients respond
to vitamin B6 therapy, there are no approved pharmaceutical
therapies for PH1.
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 or disease pathway 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 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, EU, and Brazil. Alnylam has a
deep pipeline of investigational medicines, including six 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. 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 safety and efficacy of
lumasiran as demonstrated in the ILLUMINATE-B Phase 3 study in
children under the age of six, including infants, the potential for
lumasiran to have a favorable impact on PH1 disease manifestations
and overall disease progression and management across all ages, its
plans to present the full results of the ILLUMINATE-B study,
Alnylam's expectations with respect to the review timelines for the
lumasiran NDA and MAA by the FDA and EMA, respectively, Alnylam’s
plans, assuming favorable regulatory reviews, to bring lumasiran to
patients with PH1 around the world, and expectations regarding the
continued execution on 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: the direct or indirect impact of the
COVID-19 global pandemic or any future pandemic, such as the scope
and duration of the outbreak, government actions and restrictive
measures implemented in response, material delays in diagnoses of
rare diseases, initiation or continuation of treatment for diseases
addressed by Alnylam products, or in patient enrollment in clinical
trials, potential supply chain disruptions, and other potential
impacts to Alnylam’s business, the effectiveness or timeliness of
steps taken by Alnylam to mitigate the impact of the pandemic, and
Alnylam’s ability to execute business continuity plans to address
disruptions caused by the COVID-19 or any future pandemic;
Alnylam's ability to discover and develop novel drug candidates and
delivery approaches and successfully demonstrate the efficacy and
safety of its product candidates; the pre-clinical and clinical
results for its product candidates, including lumasiran, 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, including lumasiran, or its
marketed products; obtaining, maintaining and protecting
intellectual property; intellectual property matters including
potential patent litigation relating to its platform, products or
product candidates; obtaining regulatory approval for its product
candidates, including lumasiran, and maintaining regulatory
approval and obtaining pricing and reimbursement for its products,
including ONPATTRO and GIVLAARI; progress in continuing to
establish a commercial and ex-United States infrastructure;
successfully launching, marketing and selling its approved products
globally, including ONPATTRO and GIVLAARI, and achieving net
product revenues for ONPATTRO within its revised expected range
during 2020; 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 within the ranges of guidance provided by
Alnylam through the implementation of further discipline in
operations to moderate spend and its ability to achieve a
self-sustainable financial profile in the future without the need
for future equity financing; Alnylam’s ability to establish and
maintain strategic business alliances and new business initiatives;
Alnylam's dependence on third parties, including Regeneron, for
development, manufacture and distribution of certain products,
including eye and CNS products, Ironwood, for assistance with the
education about and promotion of GIVLAARI, and Vir for the
development of ALN-COV and other potential RNAi therapeutics
targeting SARS-CoV-2 and host factors for SARS-CoV-2; 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.
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Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom (Investors and Media)
+1-617-682-4340
Josh Brodsky (Investors) +1-617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
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