Jun 17, 2019 Press Release for Alnylam
Alnylam Completes Enrollment for ILLUMINATE-A Phase 3 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 (PH1)
Jun 17, 2019
− 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 –
“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
“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
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
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
About the ILLUMINATE-A Phase 3 Study
ILLUMINATE-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
About Lumasiran
Lumasiran (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 (
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 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 (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.
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 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 (
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/20190617005215/en/
Source:
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors
and Media)
617-682-4340
Josh Brodsky
(Investors)
617-551-8276
For Media Inquiries, please contact:
Christine Lindenboom
Chief Corporate Communications Officer media@alnylam.com 617-682-4340
For Investor Inquiries, please contact:
Josh Brodsky
VP, Investor Relations & Corporate Communications investors@alnylam.com 617-551-8276
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