− Initial Results From ILLUMINATE-C Expected in
Late 2020 –
− In Phase 2 OLE, Lumasiran Treatment Resulted
in 76 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-C, a new global Phase 3 study of lumasiran, an
investigational, subcutaneously administered RNAi therapeutic in
development for the treatment of primary hyperoxaluria type 1
(PH1). The study will enroll patients of all ages with advanced
renal disease, and the primary study endpoint is the percent
reduction in plasma oxalate from baseline to six months. Alnylam
expects to report initial ILLUMINATE-C results in late 2020.
The Company also announced new positive efficacy results from
the ongoing Phase 2 open-label extension (OLE) study of lumasiran,
which were presented at the American Society of Nephrology (ASN)
2019 Annual Meeting on Saturday, November 9 in Washington, DC.
“We are pleased to announce the start of the ILLUMINATE-C trial
designed to assess the safety and efficacy of lumasiran in a PH1
patient population with advanced renal disease, including patients
of all ages and those on dialysis. This study complements our
comprehensive clinical development plan for lumasiran, led by our
ILLUMINATE-A pivotal study with results expected later this year
and our ILLUMINATE-B study in young pediatric patients. Given the
heterogeneity of the PH1 population, the ILLUMINATE trials
collectively address PH1 patients across the spectrum of age and
disease onset and severity,” 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 sustained reductions in urinary oxalate
and by the overall safety profile of lumasiran observed to
date.”
The Phase 2 OLE results were reported as of the data cut-off
date of September 12, 2019 and demonstrated a 76 percent mean
maximal reduction (range: 43-91 percent) in urinary oxalate
excretion relative to Phase 1/2 baseline values in all cohorts
(N=19)*. In the study, all patients achieved a urinary oxalate
level at or below 1.5 times the upper limit of normal (less than or
equal to 0.69 mmoL/24hr/1.73m2), and 68 percent of patients
achieved a urinary oxalate level within the normal range (less than
or equal to 0.46 mmol/24hr/1.73m2). Patients also experienced an 82
percent mean maximal reduction in urinary oxalate:creatinine ratio
(range: 62-94 percent) after lumasiran dosing across all cohorts
(N=20).
The Phase 2 OLE safety results were based on a median study
duration of 10.4 months (range: 7-17 months) since the first dose
administered in the OLE study. As of the data cut-off date, there
were no discontinuations from treatment. A single patient (1/20; 5
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. There were no other
reported SAEs in the OLE study. Adverse events (AEs) were reported
in 19/20 (95 percent) patients; most were mild in severity and
assessed as unrelated to study drug by the investigators. Injection
site reactions, which were reported in 4/20 (20 percent) patients,
were mild and did not affect dosing. Other AEs reported in more
than one patient were: headache, oropharyngeal pain (N=3);
gastroenteritis, viral gastroenteritis, pyrexia, and vomiting
(N=2). There were no clinically significant laboratory changes.
To view the results presented by Alnylam at ASN 2019 Annual
Meeting, please visit www.alnylam.com/capella.
*Patients who had a valid 24-hour urinary oxalate
assessment.
About ILLUMINATE-C Phase 3 Study The ILLUMINATE-C Phase 3
trial is a single-arm, open-label, global, multicenter study to
evaluate the efficacy and safety of lumasiran in approximately 16
patients with a documented diagnosis of PH1. Cohort A will enroll
patients with advanced disease who do not yet require dialysis and
Cohort B will enroll patients who are dialysis-dependent. During
the 6-month primary analysis period patients will receive three
monthly doses of lumasiran followed by monthly or quarterly
maintenance doses. The primary endpoint is the percentage change in
plasma oxalate from baseline to six months. Key secondary endpoints
will evaluate additional measures of plasma oxalate and changes in:
urinary oxalate, renal function, nephrocalcinosis, frequency and
mode of dialysis, frequency of renal stone events, and measures of
systemic oxalosis. For more information on ILLUMINATE-C
(NCT04152200) please visit clinicaltrials.gov, email
clinicaltrials@alnylam.com or call 877-256-9526 in North America
and +31 20 369 7861 in Europe.
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, 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-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 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 discovery
platform. Alnylam’s first commercial RNAi therapeutic is ONPATTRO®
(patisiran), approved in the U.S., EU, Canada, Japan, and
Switzerland. 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 1,200 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 Statements Various statements in
this release concerning Alnylam's future expectations, plans and
prospects, including, without limitation, Alnylam's views with
respect to 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-C
clinical studies, its views regarding the ILLUMINATE trials
collectively addressing PH1 patients across the spectrum of age and
disease onset and severity, 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, including lumasiran, 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, 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, including lumasiran, 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
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.
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.
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version on businesswire.com: https://www.businesswire.com/news/home/20191109005009/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media)
617-682-4340 Josh Brodsky (Investors) 617-551-8276
Alnylam Pharmaceuticals (NASDAQ:ALNY)
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