- Results Showed Substantial Reductions in
Plasma Oxalate Relative to Baseline in PH1 Patients with Severe
Renal Impairment, Including Those on Dialysis, and an Encouraging
Safety and Tolerability Profile -
- Alnylam Intends to File Supplemental
Regulatory Applications with the U.S. Food and Drug Administration
and the European Medicines Agency Based on ILLUMINATE-C Results in
Late 2021 -
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today positive topline results from
the ILLUMINATE-C Phase 3 open-label study of lumasiran in patients
of all ages with advanced primary hyperoxaluria type 1 (PH1)
associated with progressive decline in renal function. Lumasiran is
an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the
gene encoding glycolate oxidase (GO) – that is being investigated
for the treatment of adult and pediatric patients with advanced
PH1. Results of the primary analysis at six months demonstrated
substantial reduction in plasma oxalate from baseline in patients
(N=21) with advanced disease, including those on hemodialysis.
Elevated plasma oxalate is directly related to the pathophysiology
of oxalosis and results in systemic deposition of oxalate in
extra-renal tissues, potentially leading to bone fractures,
cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers,
and other serious manifestations1. The safety and tolerability
profile of lumasiran following six months of treatment is
encouraging across all ages, with no drug related serious adverse
events (SAEs) and injection site reactions (ISRs) as the most
common adverse event (AE).
“People with advanced PH1 suffer from severely impaired kidney
function and may require an intensive dialysis regimen as a bridge
to receiving a combined liver/kidney transplant – a procedure
associated with high morbidity and lifelong immunosuppression. In
ILLUMINATE-C, lumasiran reduced elevated levels of plasma oxalate
that can lead to the morbidity and mortality associated with
systemic oxalosis in this particularly vulnerable patient
population,” said Jeroen Valkenburg, General Manager, Lumasiran
program at Alnylam. “Through the ILLUMINATE clinical program, we
are hoping to establish that lumasiran may be a therapeutic option
for PH1 patients regardless of age or disease severity, including
patients on hemodialysis. We look forward to reporting complete
data from the ILLUMINATE-C study at a medical congress later this
year.”
“Patients with PH1 face devastating health challenges,
especially those approaching or experiencing kidney failure, and
these new results from the ILLUMINATE clinical development program
signal hope to some of the sickest and most severely impacted
individuals in this patient community,” said Kim Hollander,
Executive Director of the Oxalosis and Hyperoxaluria Foundation.
“We’re thankful that Alnylam continues to drive forth research that
may benefit the PH1 community and for conducting a study that has
the potential to help those who have the most severe form of the
disease.”
Results
ILLUMINATE-C (NCT04152200) is a single arm, open-label,
multinational Phase 3 study evaluating the safety and efficacy of
lumasiran in PH1 patients of all ages with severe renal impairment
(eGFR ≤ 45 mL/min/1.73m2 or elevated serum creatinine for patients
<12 months of age), and conducted at 13 study sites across 10
countries around the world. Cohort A enrolled six patients with
advanced PH1 who do not yet require dialysis, and Cohort B enrolled
15 patients who are hemodialysis-dependent. The dosing regimen is
based on weight with three monthly starting doses followed by
ongoing monthly or quarterly doses. The primary efficacy endpoint
for Cohort A was the percent change in plasma oxalate from baseline
to month six, and the primary endpoint for Cohort B was the percent
change in pre-dialysis plasma oxalate from baseline to month six.
Key secondary endpoints are designed to evaluate additional
measures of plasma oxalate and changes in urinary oxalate. Renal
function, frequency and mode of dialysis, frequency of renal stone
events, and measures of systemic oxalosis, including clinical
manifestations, will also be evaluated in the extension period of
the study.
At six months, treatment with lumasiran resulted in a
substantial reduction in plasma oxalate from baseline in both
dialysis-independent and -dependent patients. Lumasiran also
demonstrated positive results across key secondary endpoints,
including measures of urinary oxalate (for patients in Cohort A)
and additional measures of plasma oxalate. There were no deaths and
no drug related SAEs among enrolled patients. There were two
treatment discontinuations due to adverse events in the extension
period of the study, neither of which was drug related. The most
common drug related AEs (occurring in 10 percent or more of
patients) were ISRs reported in five patients (23.8 percent), all
of which were mild.
Based on these results, the Company plans to submit a
Supplemental New Drug Application (sNDA) for lumasiran with the
U.S. Food and Drug Administration (FDA) and a Type II Variation
with the European Medicines Agency (EMA) in late 2021. In November
2020, lumasiran was approved by the FDA for the treatment of PH1 to
lower urinary oxalate levels in pediatric and adult patients and by
the EMA for the treatment of PH1 in all age groups. Lumasiran is
marketed in the U.S. and EU as OXLUMO®. ILLUMINATE-C topline
results will be discussed during Alnylam’s Second Quarter Earnings
Conference Call on August 3rd at 8:30 am ET, and full results are
expected to be presented at a medical meeting later this year.
About Lumasiran
Lumasiran is a 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 regulatory approvals from the U.S.
Food and Drug Administration (FDA) for the treatment of PH1 to
lower urinary oxalate levels in pediatric and adult patients and
from the European Medicines Agency (EMA) for the treatment of PH1
in all age groups under the brand name OXLUMO®.
IMPORTANT SAFETY INFORMATION for OXLUMO (lumasiran)
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 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.
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
lumasiran as demonstrated in the ILLUMINATE-C Phase 3 study and the
potential for lumasiran to be a therapeutic option for PH1
regardless of age or disease severity, including for patients on
hemodialysis, expectations regarding the timing of the presentation
of full results from the ILLUMINATE-C Phase 3 study, and the timing
and planned filing of supplemental applications with FDA and EMA
based on the ILLUMINATE-C results, and Alnylam’s aspiration to
become a leading biotech company, and the planned achievement of
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.
Footnote: 1 Milliner et al., End Points for Clinical
Trials in Primary Hyperoxaluria. Clin J Am Soc Nephrol. 2020;
15(7):1056-1065.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210729005079/en/
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom (Investors and Media)
+1-617-682-4340
Josh Brodsky (Investors) +1-617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Aug 2024 to Sep 2024
Alnylam Pharmaceuticals (NASDAQ:ALNY)
Historical Stock Chart
From Sep 2023 to Sep 2024