– ALN-GO1 Achieves Human Proof of Concept with
Statistically Significant Increases in Glycolate, a Biomarker of
Effective Glycolate Oxidase Knockdown, in Healthy Adult Volunteers
–
– Single Doses of ALN-GO1 Found to be Generally
Well Tolerated –
– Company to Discuss Clinical Data during
ALN-GO1 RNAi Roundtable on Tuesday, September 27 at 10:00 a.m. ET
–
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today initial data from its ongoing
Phase 1/2 study with ALN-GO1, an investigational RNAi therapeutic
targeting glycolate oxidase (GO) for the treatment of Primary
Hyperoxaluria Type 1 (PH1). Initial clinical results were presented
today during an oral presentation at the 17th Congress of the
International Pediatric Nephrology Association (IPNA), being held
September 20 – 24, 2016 in Iguaçu, Brazil. These data were from
Part A of the ongoing Phase 1/2 study, which is being conducted in
healthy adult volunteers. Results showed that single, subcutaneous
doses of ALN-GO1 achieved dose-dependent increases in plasma and
urine glycolate. Glycolate is the substrate used by the GO enzyme
to produce excessive oxalate in patients with PH1; thus, increases
in plasma and urine glycolate in normal volunteers confirm
effective GO knockdown and provide preliminary human proof of
concept for ALN-GO1. Further, ALN-GO1 was found to be generally
well tolerated, with no serious adverse events (SAEs) reported
through the safety data transfer date. The Company plans to soon
transition to Part B of the Phase 1/2 study, which will evaluate
multiple doses of ALN-GO1 in patients with PH1.
“We believe ALN-GO1 has the potential to be a transformative
therapy for patients with PH1, a potentially fatal and ultra-rare
orphan disease that primarily afflicts children. The current
treatment approach for patients suffering from this condition is
routine dialysis and, ultimately, a dual liver and kidney
transplant, as no approved pharmaceutical options currently exist,”
said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of
R&D and Chief Medical Officer at Alnylam. “We believe these
initial results are encouraging, as they demonstrate preliminary
human proof of concept for this novel investigational RNAi
therapeutic. We now look forward to advancing this program into
patients in Part B of the ongoing Phase 1/2 study, where we aim to
achieve lowering of urinary oxalate, which is known to deposit in
kidneys and cause extensive renal and broader tissue damage in
patients with PH1.”
Initial results include all available data as of the data
transfer dates on August 17, 2016 (for safety) and September 2,
2016 (for pharmacodynamic activity). Subjects in Part A (N=32) were
enrolled in four single ascending dose cohorts (N=8 per group,
randomized 3:1 drug:placebo), with subjects receiving ALN-GO1 at
doses ranging from 0.3 to 6.0 mg/kg. ALN-GO1 administration
resulted in dose-dependent and statistically significant (nominal
two-sided p values less than 0.05) increases from baseline in
plasma and urinary glycolate as compared to placebo, with up to an
8-fold increase in plasma glycolate in the highest dose cohort.
Based on extrapolation from pre-clinical studies, the observed
level of glycolate increase would correlate with an estimated
greater than 80% silencing of the HAO1 mRNA, the transcript of the
GO enzyme. The effects of ALN-GO1 were highly durable, with levels
sustained through 85 days at the highest dose, supportive of a
once-monthly and possibly once-quarterly subcutaneous dose
regimen.
Single doses of ALN-GO1 were shown to be generally well
tolerated in healthy adult volunteers. There were no SAEs reported.
Adverse events (AEs) were reported in 88% (N=21) of ALN-GO1 treated
subjects and 63% (N=5) of placebo treated subjects. Common AEs
occurring in greater than 10% of ALN-GO1 treated subjects included
nasopharyngitis (N=6), headache (N=5), and transient injection site
pain (N=4). All AEs were mild to moderate with the exception of one
subject in the lowest dose cohort who had transient, asymptomatic
CPK elevation which was unrelated to study drug.
To view the ALN-GO1 clinical data described in this press
release, please visit www.alnylam.com/capella.
ALN-GO1 RNAi Roundtable Webinar InformationAlnylam will
review these initial clinical data and discuss PH1 and plans for
the further development of ALN-GO1 in an RNAi Roundtable webinar
this Tuesday, September 27, 2016 at 10:00 a.m. ET.
Speakers include:
- Barry Greene, President
- David Erbe, Ph.D., Director,
Research
- Guest Speaker: Sally-Anne Hulton, M.D.,
FRCPCH, MRCP, FCP, MBBCh, Consultant Paediatric Nephrologist and
Clinical Lead, Birmingham Children’s Hospital NHS Trust
- Guest Speaker: Jennifer Lawrence, M.D.
(mother of a PH1 patient)
To register for the webinar, please visit
www.alnylam.com/roundtables. A replay of the webinar and
downloadable PDF of the presentation will be available on that
website shortly after the Roundtable.
About the ALN-GO1 Phase 1/2 StudyThe Phase 1/2 trial of
ALN-GO1 is a randomized, single-blind, placebo-controlled study
being conducted in two parts. Part A is a single-dose study that
enrolled 32 healthy adult volunteers. Part B will be a multi-dose
study designed to enroll up to a total of 20 patients with PH1. The
primary objective of the study is to evaluate safety and
tolerability of single and multiple subcutaneous doses of ALN-GO1.
Secondary objectives include evaluation of pharmacokinetics and
clinical activity for ALN-GO1 as measured by its effects on plasma
glycolate and urinary oxalate levels in normal healthy volunteers
and PH1 patients, respectively.
About Primary Hyperoxaluria Type 1 (PH1) and ALN-GO1PH1
is an inborn error of metabolism. Specifically, PH1 is an autosomal
recessive disorder of glyoxylate metabolism, where hepatic
detoxification of glyoxylate is impaired due to mutation of the
AGXT gene – which encodes the liver peroxisomal alanine-glyoxylate
aminotransferase (AGT) enzyme – resulting in excessive oxalate
production. Excess oxalate in PH1 patients results in the
deposition of calcium oxalate crystals in the kidneys and urinary
tract and can lead to the formation of recurrent kidney stones or
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 excreted, potentially resulting in
subsequent accumulation and crystallization in bones, eyes, skin,
and heart, leading to severe illness and death. About 50 percent of
patients will have kidney failure by age 15, and about 80 percent
will have end stage renal disease by age 30. Current treatment
options are very limited, and include frequent renal dialysis or
combined organ transplantation of liver and kidneys, a procedure
with high morbidity that is limited due to organ availability.
Although a small minority of patients respond to Vitamin B6
supplementation, there are no approved pharmaceutical therapies for
PH1.
ALN-GO1 is an investigational RNAi therapeutic, currently in
early stage clinical development. The safety and efficacy of
ALN-GO1 have not been evaluated by the U.S. Food and Drug
Administration or any other health authority.
Sanofi Genzyme AllianceIn January 2014, Alnylam and
Sanofi Genzyme, the specialty care global business unit of Sanofi,
formed an alliance to accelerate and expand the development and
commercialization of RNAi therapeutics across the world. The
alliance is structured as a multi-product geographic alliance in
the field of rare diseases. Alnylam retains product rights
in North America and Western Europe, while Sanofi
Genzyme obtained the right to access certain programs in Alnylam's
current and future Genetic Medicines pipeline, including ALN-GO1,
in the rest of the world (ROW) through the end of 2019, together
with certain broader co-development/co-commercialization rights and
global product rights for certain products, including ALN-GO1.
About GalNAc Conjugates and Enhanced Stabilization Chemistry
(ESC)-GalNAc ConjugatesGalNAc-siRNA conjugates are a
proprietary Alnylam delivery platform and are designed to achieve
targeted delivery of RNAi therapeutics to hepatocytes through
uptake by the asialoglycoprotein receptor. Alnylam's Enhanced
Stabilization Chemistry (ESC)-GalNAc-conjugate technology enables
subcutaneous dosing with increased potency and durability, and a
wide therapeutic index. This delivery platform is being employed in
nearly all of Alnylam's pipeline programs, including programs in
clinical development.
About RNAiRNAi (RNA interference) is a revolution in
biology, representing a breakthrough in understanding how genes are
turned on and off in cells, and a completely new approach to drug
discovery and development. Its discovery has been heralded as "a
major scientific breakthrough that happens once every decade or
so," and represents one of the most promising and rapidly advancing
frontiers in biology and drug discovery today which was awarded the
2006 Nobel Prize for Physiology or Medicine. RNAi is a natural
process of gene silencing that occurs in organisms ranging from
plants to mammals. By harnessing the natural biological process of
RNAi occurring in our cells, the creation of a major new class of
medicines, known as RNAi therapeutics, is on the horizon. Small
interfering RNA (siRNA), the molecules that mediate RNAi and
comprise Alnylam's RNAi therapeutic platform, target the cause of
diseases by potently silencing specific mRNAs, thereby preventing
disease-causing proteins from being made. RNAi therapeutics have
the potential to treat disease and help patients in a fundamentally
new way.
About Alnylam PharmaceuticalsAlnylam is a
biopharmaceutical company developing novel therapeutics based on
RNA interference, or RNAi. The company is leading the translation
of RNAi as a new class of innovative medicines. Alnylam's pipeline
of investigational RNAi therapeutics is focused in 3 Strategic
Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline
of RNAi therapeutics for the treatment of rare diseases;
Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics
toward genetically validated, liver-expressed disease targets for
unmet needs in cardiovascular and metabolic diseases; and Hepatic
Infectious Disease, with a pipeline of RNAi therapeutics that
address the major global health challenges of hepatic infectious
diseases. In early 2015, Alnylam launched its "Alnylam 2020"
guidance for the advancement and commercialization of RNAi
therapeutics as a whole new class of innovative medicines.
Specifically, by the end of 2020, Alnylam expects to achieve a
company profile with 3 marketed products, 10 RNAi therapeutic
clinical programs – including 4 in late stages of development –
across its 3 STArs. The company's demonstrated commitment to RNAi
therapeutics has enabled it to form major alliances with leading
companies including Ionis, Novartis, Roche, Takeda, Merck,
Monsanto, The Medicines Company, and Sanofi Genzyme. In addition,
Alnylam holds an equity position in Regulus Therapeutics Inc., a
company focused on discovery, development, and commercialization of
microRNA therapeutics. Alnylam scientists and collaborators have
published their research on RNAi therapeutics in over 200
peer-reviewed papers, including many in the world's top scientific
journals such as Nature, Nature Medicine, Nature Biotechnology,
Cell, New England Journal of Medicine, and The Lancet. Founded in
2002, Alnylam maintains headquarters in Cambridge, Massachusetts.
For more information about Alnylam's pipeline of investigational
RNAi therapeutics, please visit www.alnylam.com.
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 investigational RNAi therapeutics,
including ALN-GO1, its expectations regarding the timing of
clinical studies and the expected timing for the presentation of
clinical data from these studies, including from Part B of the
ongoing Phase 1/2 study of ALN-GO1, its expectations regarding its
STAr pipeline growth strategy, and its plans regarding
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
our 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, 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.
The scientific information discussed in this news release
relating to Alnylam’s investigational therapeutic, ALN-GO1, is
preliminary and investigative. ALN-GO1 has not been approved by the
U.S. Food and Drug Administration, European Medicines Agency, or
any other regulatory authority and no conclusions can or should be
drawn regarding the safety or effectiveness of ALN-GO1.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20160924005014/en/
Alnylam Pharmaceuticals, Inc.(Investors and
Media)Christine Regan Lindenboom, 617-682-4340or(Investors)Josh
Brodsky, 617-551-8276
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