− On Track to Report ILLUMINATE-A Topline
Results in Late 2019 –
− In Addition, Company Reports Final Positive
Results from Phase 1/2 Study of Lumasiran –
Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading
RNAi therapeutics company, announced today that it has achieved
full patient enrollment in its ILLUMINATE-A Phase 3 study of
lumasiran, an investigational RNAi therapeutic targeting glycolate
oxidase for the treatment of adults and children with primary
hyperoxaluria type 1 (PH1). The study enrolled patients across 16
sites in eight countries. Alnylam is on track to report topline
results from ILLUMINATE-A expected in late 2019 and, if positive,
to submit filings for global regulatory approvals starting in early
2020. The Company also announced complete positive results from its
Phase 1/2 clinical study and reiterated positive results from its
ongoing Phase 2 open-label extension (OLE) study of lumasiran.
Results will be presented at the 2019 Oxalosis & Hyperoxaluria
(OHF) International Workshop being held in Boston, on June
21-22.
“We are pleased to have reached two important milestones for our
PH1 program, timely completion of enrollment in ILLUMINATE-A – our
Phase 3 pivotal study in adults and children – and successful
completion of our Phase 1/2 study with positive final results,”
said Pritesh J. Gandhi, PharmD, Vice President and General Manager,
Lumasiran program at Alnylam. “We look forward to reporting topline
results from the ILLUMINATE-A study expected in late 2019 and
believe that lumasiran has the potential to provide a clinically
meaningful treatment option for patients living with PH1.”
“With positive Phase 1/2 results where oxalate reduction was
observed for every patient and with ongoing ILLUMINATE Phase 3
trials, we are hopeful for the future of our PH1 patient community
who have limited options available to them,” said Kim Hollander,
Executive Director, Oxalosis & Hyperoxaluria Foundation. “We
look forward to continuing to work with Alnylam as they advance
lumasiran through multiple Phase 3 studies designed to address the
full spectrum of patients affected by PH1.”
In final Phase 1/2 study results, lumasiran demonstrated a mean
maximal reduction in urinary oxalate of 75 percent (range: 43-92
percent) relative to baseline across all cohorts (1 mg/kg monthly,
3 mg/kg monthly, and 3 mg/kg quarterly; N=20). At 28 days post the
last dose, the mean reduction relative to baseline was 66 percent.
All patients (100 percent) achieved oxalate lowering to less than
1.5 times upper limit of normal (less than or equal to 0.69
mmol/24hr/1.73m2). Among patients receiving 3 mg/kg monthly or
quarterly doses of lumasiran (N=12), 92 percent achieved urinary
oxalate levels within the normal range (less than 0.46
mmol/24hr/1.73m2). Furthermore, lumasiran-treated patients across
all cohorts (N=20) experienced a mean maximal decrease of 77
percent (range: 50-95 percent) in the ratio of urinary oxalate to
creatinine – an additional measure of oxalate reduction that
addresses the variability that is inherent in 24-hour urine
collections.
Lumasiran results showed an acceptable safety and tolerability
profile, with PH1 patients on study for a median of 9.8 months
(range: 5.6 to 15.2 months); there were no study discontinuations.
Serious adverse events (SAEs) were reported for one patient (33
percent) receiving placebo and four patients (20 percent) receiving
lumasiran; none were related to study drug. The placebo patient
experienced acute pyelonephritis and kidney stones. The lumasiran
patients with SAEs included one patient with vomiting, one patient
with abdominal pain, fever and vomiting, one patient with
gastroenteritis, and one patient with kidney stones. Adverse events
(AEs) were reported in two (66.7 percent) patients during placebo
dosing and 20 (100 percent) patients after lumasiran dosing. The
majority of AEs were mild or moderate in severity and were assessed
as unrelated to study drug. Severe AEs were reported in one (33
percent) patient during placebo dosing (acute pyelonephritis) and
one (5 percent) patient after lumasiran dosing (kidney stone); none
were considered related to study drug by investigator. AEs reported
in more than three patients receiving lumasiran were pyrexia (N=6);
vomiting, cough, abdominal pain, headache (N=5 each); and rhinitis
and nephrolithiasis (N=4 each). Self-limiting injection site
reactions (ISRs) were reported in three (15 percent) patients
receiving lumasiran; all mild or moderate and with none affecting
dosing. Lumasiran was not associated with any clinically
significant adverse laboratory findings, including liver function
tests.
As previously reported, all patients (100 percent) who completed
Phase 1/2 (N=20) continue dosing in the ongoing Phase 2 OLE phase
of the study. As of February 2019, patients in the Phase 2 OLE
study have received lumasiran for a median of four months (range:
0.03–8.36; N=18). Lumasiran dosing across all evaluable cohorts
(N=9) resulted in mean maximal reduction in urinary oxalate of 72
percent (range: 41-90 percent) relative to Phase 1/2 baseline
levels. Multiple doses of lumasiran demonstrated an acceptable
safety and tolerability profile in patients with PH1, with no drug
related SAEs and no discontinuations from study treatment.
The Company also recently presented a case study of a healthy
human with mutations in the HAO1 gene, a validated target
for the treatment of PH1, as well as results from research on the
diagnostic journey of PH1 at the 56th Congress of the European
Renal Association (ERA) and European Dialysis and Transplant
Association (EDTA) held on June 13-16, 2019 in Budapest, Hungary.
To view the results presented by Alnylam at the ERA-EDTA Congress,
please visit www.alnylam.com/capella.
About the ILLUMINATE-A Phase 3 StudyILLUMINATE-A is a six
month randomized, double-blind, placebo-controlled, global,
multicenter Phase 3 study to evaluate the efficacy and safety of
lumasiran in approximately 30 patients with a documented diagnosis
of PH1, followed by a 54 month extension period where all patients
will receive lumasiran. Patients are randomized 2:1 to receive
three monthly doses of lumasiran or placebo at 3 mg/kg followed by
quarterly maintenance doses. The primary endpoint is the percent
change in 24-hour urinary oxalate excretion from months 3 to 6
relative to baseline in the patients treated with lumasiran as
compared to placebo. Key secondary and exploratory endpoints will
evaluate additional measures of urinary oxalate, plasma oxalate,
estimated glomerular filtration rate (eGFR), safety and
tolerability, and quality of life. At month 6, the patients
receiving placebo will cross over to receive lumasiran for
long-term follow up. For more information on ILLUMINATE-A
(NCT03681184) please visit 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 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/ocular diseases. Based on
Nobel Prizewinning science, RNAi therapeutics represent a powerful,
clinically validated approach for the treatment of diseases with
high unmet need. ONPATTRO® (patisiran) is the first-ever RNAi
therapeutic approved by the U.S. FDA for the treatment of the
polyneuropathy of hereditary transthyretin-mediated (hATTR)
amyloidosis in adults and by the EMA 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 in Phase 3 studies and one in registration.
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. Headquartered in Cambridge, MA,
Alnylam employs over 1,200 people worldwide. 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 potential for lumasiran to address the significant
unmet need that PH1 represents, its plans to present study data and
plans and expected timing to report topline results from
ILLUMINATE-A and, if positive, submit filings for regulatory
approval, expectations regarding Alnylam’s global commercialization
of lumasiran, if approved, 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 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/20190617005215/en/
Alnylam Pharmaceuticals, Inc.Christine Regan
Lindenboom(Investors and Media)617-682-4340
Josh Brodsky(Investors)617-551-8276
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