– OXLUMO Demonstrated Improvements in
Nephrocalcinosis in Patients with Primary Hyperoxaluria Type 1
After 12 Months of Treatment –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today positive early results on
clinical outcome measures from the 12-month analysis of
ILLUMINATE-A Phase 3 study of OXLUMO® (lumasiran), an RNAi
therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene
encoding glycolate oxidase (GO) – for the treatment of primary
hyperoxaluria type 1 (PH1). These data were presented at the
American Society of Pediatric Nephrology (ASPN)/Pediatric Academic
Societies (PAS) virtual meeting being held on April 30–May 4,
2021.
As previously reported, treatment with OXLUMO significantly
reduced urinary oxalate levels in infants1, children1,2 and adults2
with PH1 in the ILLUMINATE-A and ILLUMINATE-B studies. OXLUMO also
demonstrated an acceptable safety profile across age groups, with
injection site reactions as the most common drug-related adverse
reaction. New results from ILLUMINATE-A showed that treatment with
OXLUMO for 12 months was associated with evidence of improvements
in nephrocalcinosis in one or both kidneys, relative to
baseline.
“Nephrocalcinosis is a key indicator of disease severity in
PH1,” said Jeffrey M. Saland, M.D., Professor and Chief, Pediatric
Nephrology and Hypertension, Jack and Lucy Clark Department of
Pediatrics, Mount Sinai Kravis Children’s Hospital, New York City
and Investigator on the ILLUMINATE-A trial. “Thus, unilateral and
bilateral improvements in nephrocalcinosis in some patients treated
with OXLUMO are a welcome observation and are consistent with our
expectation of the potential clinical impact of a sustained and
substantial reduction in urinary oxalate levels.”
“We are thrilled to be presenting positive nephrocalcinosis data
from our ILLUMINATE-A study,” said Pushkal Garg, M.D., Chief
Medical Officer at Alnylam. “These early data provide emerging
evidence demonstrating improvements in nephrocalcinosis in some
patients. Notably, the majority of patients with baseline
nephrocalcinosis and available ultrasounds experienced improvement,
often in both kidneys, after 12 months of treatment – an
encouraging sign indicating the potential of OXLUMO to improve
renal outcome measures in patients with PH1. We look forward to
reporting additional data later in the year.”
Results
Among 24 patients in ILLUMINATE-A who had been treated with
lumasiran for 12 months and had valid renal ultrasounds at
baseline, 46 percent (11/24) of patients experienced improvement in
nephrocalcinosis grade relative to baseline, 17 percent (4/24)
remained stable, and 13 percent (3/24) experienced worsening; 25
percent (6/24) did not have ultrasounds available at 12 months. Of
14 patients with baseline nephrocalcinosis and available
ultrasounds, 79 percent (11/14) showed improvement relative to
baseline, and of those who improved, 73 percent (8/11) improved in
both kidneys. Additional data were presented regarding effects on
estimated glomerular filtration rate (eGFR) and kidney stone
events.
To view the full results presented at the virtual ASPN congress,
please visit www.alnylam.com/capella.
IMPORTANT SAFETY INFORMATION
Adverse Reactions
The most common adverse reaction that occurred in patients
treated with OXLUMO was injection site reaction (38%). Symptoms
included erythema, pain, pruritus, and swelling.
Pregnancy and Lactation
No data are available on the use of OXLUMO in pregnant women. No
data are available on the presence of OXLUMO in human milk or its
effects on breastfed infants or milk production. Consider the
developmental and health benefits of breastfeeding along with the
mother’s clinical need for OXLUMO and any potential adverse effects
on the breastfed child from OXLUMO or the underlying maternal
condition.
For additional information about OXLUMO, please see the full
Prescribing Information.
About OXLUMO® (lumasiran)
OXLUMO is an RNAi therapeutic targeting hydroxyacid oxidase 1
(HAO1) for the treatment of primary hyperoxaluria type 1 (PH1) to
lower urinary oxalate levels in pediatric and adult patients. HAO1
encodes glycolate oxidase (GO), an enzyme upstream of the
disease-causing defect in PH1. OXLUMO works by degrading HAO1
messenger RNA and reducing the synthesis of GO, which inhibits
hepatic production of oxalate – the toxic metabolite responsible
for the clinical manifestations of PH1. In the pivotal ILLUMINATE-A
study, OXLUMO was shown to significantly reduce levels of urinary
oxalate relative to placebo, with the majority of patients reaching
normal or near-normal levels. Injection site reactions (ISRs) were
the most common drug-related adverse reaction. In the ILLUMINATE-B
pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety
profile consistent with that observed in ILLUMINATE-A. OXLUMO
utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc
conjugate technology designed to increase potency and durability.
OXLUMO is administered via subcutaneous injection once monthly for
three months, then once quarterly thereafter at a dose based on
actual body weight. For patients who weigh less than 10 kg, ongoing
dosing remains monthly. OXLUMO should be administered by a
healthcare professional. For more information about OXLUMO, visit
OXLUMO.com.
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, age six and older, with a
documented diagnosis of PH1. Patients were randomized 2:1 to
receive three monthly doses of lumasiran or placebo followed by
quarterly 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 ILLUMINATE-B Phase 3 Study
ILLUMINATE-B (NCT03905694) is a single arm, open-label,
multicenter Phase 3 trial to evaluate the efficacy and safety of
lumasiran in 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).
About Primary Hyperoxaluria Type 1 (PH1)
PH1 is an ultra-rare genetic disease that affects an estimated
one to three individuals per million in the United States and
Europe. PH1 is characterized by oxalate overproduction in the
liver. The excess oxalate 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. PH1 is
associated with a progressive decline in kidney function, which
exacerbates the disease as the excess oxalate can no longer be
effectively excreted, resulting in subsequent accumulation and
deposition of oxalate in bones, eyes, skin, and heart, leading to
severe illness and death. Management options to date were limited
to hyperhydration, crystallization inhibitors and, in a minority of
patients with a specific genotype, pyridoxine (vitamin B6). These
measures do not adequately address oxalate overproduction but
instead help to delay inevitable progression to kidney failure and
the need for intensive dialysis as a bridge to a dual or sequential
liver/kidney transplant. Liver transplantation is the only
intervention that addresses the underlying metabolic defect, but is
associated with high morbidity and mortality, and life-long
immunosuppression. Until today, there were 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), GIVLAARI®
(givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) being
developed and commercialized by Alnylam’s partner Novartis. Alnylam
has a deep pipeline of investigational medicines, including six
product candidates that are in late-stage development. Alnylam is
executing on its “Alnylam P5x25” strategy to deliver transformative
medicines in both rare and common diseases benefiting patients
around the world through sustainable innovation and exceptional
financial performance, resulting in a leading biotech profile.
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, on
LinkedIn, or on Instagram.
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 OXLUMO
as demonstrated after 12-months of treatment in the ILLUMINATE-A
Phase 3 study and expectations regarding the timing for reporting
additional data on clinical outcomes measures, the potential
clinical impact of treatment with OXLUMO as demonstrated by
unilateral and bilateral improvements in nephrocalcinosis in some
patients, and Alnylam’s ability to achieve its “Alnylam P5x25”
strategy, 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 on
Alnylam’s business, results of operations and financial condition
and the effectiveness or timeliness of Alnylam’s efforts to
mitigate the impact of the 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; actions or advice of regulatory agencies and Alnylam’s
ability to obtain and maintain regulatory approval for its product
candidates, as well as favorable pricing and reimbursement;
successfully launching, marketing and selling its approved products
globally; delays, interruptions or failures in the manufacture and
supply of its product candidates or its marketed products;
obtaining, maintaining and protecting intellectual property;
Alnylam’s ability to successfully expand the indication for
ONPATTRO in the future; Alnylam's ability to manage its growth and
operating expenses through disciplined investment in operations and
its ability to achieve a self-sustainable financial profile in the
future without the need for future equity financing; Alnylam’s
ability to maintain strategic business collaborations; Alnylam's
dependence on third parties for the development and
commercialization of certain products, including Novartis, Sanofi,
Regeneron and Vir; the outcome of litigation; the potential impact
of current and the risk of future 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 its other SEC filings. 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.
This release discusses the use of a previously approved RNAi
therapeutic in continued development and is not intended to convey
conclusions about efficacy or safety as to these uses. There is no
guarantee that the data described in this release will result in
expanded use of this commercial product, will successfully complete
clinical development or will gain health authority approval.
Footnotes: 1See About ILLUMINATE-B for patient population
and study endpoints 2See About ILLUMINATE-A for patient population
and study endpoints
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Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media) +1-617-682-4340
Josh Brodsky (Investors) +1-617-551-8276
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