− Lumasiran is the First Potential Therapeutic
to Demonstrate Substantial Reduction in Urinary Oxalate Excretion
–
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today announced the completion of the rolling
submission of a New Drug Application (NDA) to the U.S. Food and
Drug Administration (FDA) for lumasiran, an investigational RNAi
therapeutic targeting glycolate oxidase (GO), in development for
the treatment of primary hyperoxaluria type 1 (PH1). PH1 is an
ultra-rare, life-threatening disease impacting the kidneys and
other vital organs; it affects infants, children, and adults.
In the U.S., lumasiran has previously received Pediatric Rare
Disease Designation, Orphan Drug Designation, and Breakthrough
Therapy Designation for the treatment of PH1, based on data showing
a substantial reduction in urinary oxalate, the key toxic
metabolite responsible for the clinical manifestations of the
disease.
The Company also announced the submission of a Marketing
Authorization Application (MAA) to the European Medicines Agency
(EMA) for lumasiran for the treatment of PH1. Lumasiran has been
granted Priority Medicines (PRIME) Designation by the EMA as well
as Orphan Drug Designation in the European Union. Lumasiran 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. Accelerated assessment potentially
provides a reduced review timeline from 210 to 150 days once the
MAA is filed and validated.
“PH1 can affect people of all ages, from infants, to children,
to adults, as well as their families and those who care for them.
PH1 causes a progressive decline in kidney function and can lead to
end-stage renal disease, at which point patients need intensive
dialysis until they are able, and eligible, to receive dual
liver/kidney transplantation,” said Pritesh J. Gandhi, PharmD.,
Vice President and General Manager, Lumasiran Program at Alnylam.
“Given the unmet need in PH1 and the encouraging lumasiran Phase 3
data, Alnylam maintained its commitment to meet our target dates
for timely NDA and MAA submissions, even under the challenging
prevailing circumstances. We now look forward to working closely
with the FDA and EMA to bring this innovative medicine to patients
and their families.”
Topline data from the pivotal ILLUMINATE-A Phase 3 study show
that lumasiran met its primary efficacy endpoint and all tested
secondary endpoints. Specifically, lumasiran met the primary
efficacy endpoint of percent change from baseline, relative to
placebo, in 24-hour urinary oxalate excretion averaged across
Months 3 to 6 (p value less than 0.0001). Epidemiological data show
a strong relationship between urinary oxalate reduction and
long-term kidney function loss. The study also achieved
statistically significant results for all six tested secondary
endpoints (p value less than or equal to 0.001), including the
proportion of patients achieving a near-normalization or
normalization of urinary oxalate, relative to placebo. Lumasiran
demonstrated an encouraging safety and tolerability profile
consistent with previous reports from earlier studies.
Complete results from the ILLUMINATE-A study included as part of
the FDA rolling submission and EMA filing applications are planned
to be presented at the OxalEurope International Congress, currently
scheduled for June 16, 2020 in Amsterdam.
About Lumasiran
Lumasiran is an investigational, subcutaneously administered
RNAi therapeutic targeting glycolate oxidase (GO), in development
for the treatment of primary hyperoxaluria type 1 (PH1). GO is
encoded by the hydroxyacid oxidase 1 (HAO1) gene. 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 quarterly subcutaneous maintenance dosing with increased
potency and durability and a wide therapeutic index. Lumasiran has
received both U.S. and EU Orphan Drug Designations, a Breakthrough
Therapy Designation and pediatric rare disease designation from the
U.S. Food and Drug Administration (FDA), and a Priority Medicines
(PRIME) designation from the European Medicines Agency (EMA). The
safety and efficacy of lumasiran have not been evaluated by the
FDA, EMA or any other health authority.
About the ILLUMINATE-A Phase 3 Study
ILLUMINATE-A (NCT03681184) is a randomized, double-blind,
placebo-controlled trial, designed to enroll approximately 30
patients with PH1 ages six and above, at 16 study sites, in eight
countries around the world. To date, this is the largest
interventional study conducted specifically in PH1. Patients were
randomized 2:1 to lumasiran or placebo, with lumasiran administered
at 3 mg/kg monthly for three months followed by quarterly
maintenance doses. The primary endpoint for the study was the
percent change from baseline in 24-hour urinary oxalate excretion
averaged across Months 3 to 6 in patients treated with lumasiran as
compared to placebo. At six months, lumasiran met the primary
endpoint in patients with PH1 (p value less than 0.0001) and
achieved statistically significant results for all six
hierarchically-tested secondary endpoints (p value less than or
equal to 0.001), including the proportion of lumasiran patients
that achieved near-normalization or normalization of urinary
oxalate levels, relative to placebo.
There were no serious or severe adverse events in the study, and
results showed that lumasiran was generally well tolerated with an
overall safety profile generally consistent with that observed in
Phase 1/2 and open-label extension studies of lumasiran. Full
ILLUMINATE-A study results will be presented in 2020.
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 minority of patients are fully
responsive 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 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 and the EU. 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.
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 implications of the positive
topline results from the ILLUMINATE-A study, the submissions of an
MAA to the EMA and an NDA to the FDA, the potential for a reduced
review timeline by the EMA, as well as the pediatric rare disease
designation for lumasiran from the FDA, 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: potential risks to Alnylam’s
business, activities and prospects as a result of the COVID-19
pandemic, or delays or interruptions resulting therefrom; 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, 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 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 its expected guidance
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 certain products, including eye and CNS 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
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/20200407005239/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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