− All Patients in Phase 1/2 Study Have Now
Transitioned into Phase 2 OLE –
− Lumasiran Treatment Resulted in 72 Percent
Mean Maximal Reduction in Urinary Oxalate Relative to Phase 1/2
Baseline –
Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading
RNAi therapeutics company, announced today that the Company has
initiated ILLUMINATE-B, a global Phase 3 pediatric study of
lumasiran, an investigational, subcutaneously administered RNAi
therapeutic in development for the treatment of primary
hyperoxaluria type 1 (PH1). The study will enroll approximately
eight patients with PH1 under six years of age. The primary
endpoint is the percent reduction in urinary oxalate from baseline
to six months. The Company expects to report initial ILLUMINATE-B
results in mid-2020.
The Company also announced new positive efficacy results from
the ongoing Phase 2 open-label extension (OLE) study of lumasiran.
The results were presented at the International Society of
Nephrology (ISN) 2019 Annual Meeting held on April 13-16 in
Melbourne, Australia.
“We are pleased to start the ILLUMINATE-B pediatric trial, an
important step forward in our goal to assess the safety and
efficacy of lumasiran across the PH1 age and disease severity
continuum, including patients in early infancy. This study adds to
our overall clinical development plan for lumasiran, led by our
ILLUMINATE-A pivotal study with results expected by year-end 2019,”
said Pritesh J. Gandhi, PharmD, Vice President and General Manager,
Lumasiran program at Alnylam. “We are also pleased to report new
results from our Phase 2 OLE study, and are encouraged by the
consistently sustained reductions we observe in urinary oxalate and
by the overall safety profile of lumasiran observed thus far.”
All patients (N=20) from the Phase 1/2 study of lumasiran have
now transitioned to the Phase 2 OLE study designed to evaluate
long-term safety and efficacy of lumasiran. The new Phase 2 OLE
results were reported with 18 patients dosed in the OLE as of the
data cut-off date of February 8. Patients were on a range of
lumasiran doses and regimens (1.0 mg/kg monthly, 3.0 mg/kg monthly,
and 3.0 mg/kg quarterly).
There were no discontinuations from study treatment. A single
patient (1/18; 5.6 percent) reported two serious adverse events
(SAEs) of traumatic brain injury and bone contusion sustained in a
car accident; neither was assessed as related to study drug.
Adverse events (AEs) were reported in 12/18 (66.7 percent)
patients. Injection site reactions were reported in 3/18 (16.7
percent) patients; all were mild and assessed as related to study
drug. There were no clinically significant laboratory changes.
Lumasiran demonstrated a 72 percent mean maximal reduction
(range: 41-90 percent) in urinary oxalate excretion relative to
Phase 1/2 baseline values across all dose cohorts (N=9). The mean
reduction relative to baseline at Day 85 was 69 percent (N=7).
Lumasiran also demonstrated a mean maximal reduction in urinary
24-hour oxalate:creatinine ratio of 77 percent (range: 57-91
percent) relative to Phase 1/2 baseline values across all dose
cohorts (N=10). The mean reduction relative to baseline at Day 85
was 70 percent (N=9).
To view the results presented by Alnylam at ISN 2019 Annual
Meeting, please visit www.alnylam.com/capella.
About ILLUMINATE-B Phase 3 StudyThe ILLUMINATE-B Phase 3
trial is an open-label, global, multicenter study to evaluate the
efficacy and safety of lumasiran in approximately eight patients
less than six years of age with a documented diagnosis of PH1.
Dosing regimen will be based on patient weight. The primary
endpoint is the reduction of urinary oxalate at six months relative
to baseline. Key secondary and exploratory endpoints will evaluate
additional measures of urinary oxalate, estimated glomerular
filtration rate (eGFR), safety and tolerability, and quality of
life. For more information on ILLUMINATE-B (NCT03905694) please
visit www.clinicaltrials.gov, email clinicaltrials@alnylam.com or
call 877-256-9526 in North America and +31 20 369 7861 in
Europe.
About LumasiranLumasiran (formerly known as ALN-GO1) is
an investigational RNAi therapeutic targeting glycolate oxidase
(GO) in development for the treatment of Primary Hyperoxaluria Type
1 (PH1). Lumasiran is designed to reduce hepatic levels of the GO
enzyme, thereby depleting the substrate necessary for the
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, a Breakthrough Therapy 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 Primary Hyperoxaluria Type 1 (PH1)PH1 is an
ultra-orphan 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 RNAiRNAi (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 PharmaceuticalsAlnylam (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 discovery
platform. Alnylam’s first U.S. FDA-approved RNAi therapeutic is
ONPATTRO® (patisiran) lipid complex injection available in the U.S.
for the treatment of the polyneuropathy of hereditary
transthyretin-mediated (hATTR) amyloidosis in adults. In the EU,
ONPATTRO is approved for the treatment of hATTR amyloidosis in
adults with stage 1 or stage 2 polyneuropathy. Alnylam has a deep
pipeline of investigational medicines, including five product
candidates that are in late-stage development. Looking forward,
Alnylam will continue to execute 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 1,000 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 StatementsVarious statements in
this release concerning Alnylam's future expectations, plans and
prospects, including, without limitation, Alnylam's views with
respect to the potency, durability and therapeutic index of
lumasiran and the potential for lumasiran to address the
significant unmet needs of PH1 patients, its expectations regarding
the timing for reporting results from the ILLUMINATE-A and
ILLUMINATE-B clinical studies, and expectations regarding "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, progress in establishing a commercial and ex-United
States infrastructure, successfully launching, marketing and
selling its approved products globally, 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, 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 for development, manufacture
and distribution of products, 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.
Lumasiran has not been approved by the FDA, EMA, or any
other regulatory authority and no conclusions can or should be
drawn regarding the safety or effectiveness of this investigational
therapeutic.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190415005232/en/
Alnylam Pharmaceuticals, Inc.Christine Regan
Lindenboom(Investors and Media)617-682-4340
Josh Brodsky(Investors)617-551-8276
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