− Lumasiran Met Primary and All Tested
Secondary Endpoints, with Significant Reduction in Urinary Oxalate
Levels Relative to Placebo –
− Alnylam Intends to File New Drug Application
(NDA) and Marketing Authorisation Application (MAA) in Early 2020
–
− Full Results to be Presented at OxalEurope
International Congress in March 2020 –
− Alnylam to Host Conference Call Today at 8:00
am ET –
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, announced today that the ILLUMINATE-A Phase 3
study of lumasiran, an investigational RNAi therapeutic targeting
glycolate oxidase (GO) in development for the treatment of primary
hyperoxaluria type 1 (PH1), met its primary efficacy endpoint and
all tested secondary endpoints. Specifically, lumasiran met the
primary efficacy endpoint of percent change from baseline, relative
to placebo, in 24-hour urinary oxalate excretion averaged across
months 3 to 6 (p less than 0.0001). The study also achieved
statistically significant results for all six tested secondary
endpoints (p less than or equal to 0.001). Lumasiran also
demonstrated an encouraging safety and tolerability profile. Based
on these results, the Company plans to submit a New Drug
Application (NDA) and file a Marketing Authorisation Application
(MAA) for lumasiran in early 2020.
“We are very pleased to report positive topline Phase 3 results
for lumasiran, our third wholly owned investigational RNAi
therapeutic. Patients living with PH1 and their families are faced
with the burden of recurrent and painful stone events and a
progressive and unpredictable decline in kidney function that
ultimately results in end-stage renal disease and the need for
intensive dialysis as a bridge to dual liver/kidney
transplantation. The results from ILLUMINATE-A demonstrate that
lumasiran can significantly reduce the hepatic production of
oxalate, which we believe can thereby address the underlying
pathophysiology of PH1,” said Akshay Vaishnaw, M.D., Ph.D.,
President of R&D at Alnylam. “Further, we are encouraged by the
safety and tolerability profile of lumasiran and believe this
investigational medicine has the potential to have a meaningful
clinical impact on patients living with PH1. We look forward to
submitting regulatory filings in early 2020 and advancing this
highly needed medicine one step closer to patients. Finally, we
extend our deepest gratitude to the patients, caregivers,
investigators, and study staff who participated in ILLUMINATE-A and
contributed to what we believe is an important medical advance for
the treatment of PH1.”
“The ILLUMINATE-A results represent a significant landmark for
the PH1 patient community. These patients live with the angst of
not knowing when that next kidney stone will come or for how long
their kidneys will keep working, and they grapple with the
possibility of needing new organs. We have lived with the hope that
someday patients living with PH1 and their families would finally
have a treatment with the potential to have a positive impact on
their health and alleviate some of that angst,” said Kim Hollander,
Executive Director of the Oxalosis and Hyperoxaluria Foundation.
“Today we are hopeful that we are much closer to that day than we
have ever been.”
“Lumasiran results in ILLUMINATE-A mark our third positive Phase
3 study readout in 2019, positioning Alnylam with the potential for
four marketed products by the end of 2020, assuming positive
regulatory reviews. We believe this achievement also provides
further support of our relatively high product development success
rate linked to selection of genetically validated targets and a
modular and reproducible platform,” said John Maraganore, Ph.D.,
Chief Executive Officer of Alnylam. “With these results in hand, we
believe that we’re on track to exceed our Alnylam 2020 guidance,
building – by the end of 2020 – a global, multi-product,
commercial-stage company with a robust portfolio of clinical-stage
programs for future growth and an organic product engine for
sustainable innovation and patient impact.”
ILLUMINATE-A Topline Study Results ILLUMINATE-A
(NCT03681184), a randomized, double-blind, placebo-controlled
trial, designed to enroll approximately 30 patients with PH1 ages
six and above, at 16 study sites, in eight countries around the
world, is the largest interventional study conducted specifically
in PH1. Patients were randomized 2:1 to lumasiran or placebo, with
lumasiran administered at 3 mg/kg monthly for three months followed
by quarterly maintenance doses. The primary endpoint for the study
was the percent change from baseline in 24-hour urinary oxalate
excretion averaged across months 3 to 6 in patients treated with
lumasiran as compared to placebo. At six months, lumasiran met the
primary endpoint in patients with PH1 (p less than 0.0001) and
achieved statistically significant results for all six
hierarchically-tested secondary endpoints (p less than or equal to
0.001), including the proportion of lumasiran patients that
achieved near-normalization or normalization of urinary oxalate
levels, relative to placebo.
There were no serious or severe adverse events in the study, and
results showed that lumasiran was generally well tolerated with an
overall profile generally consistent with that observed in Phase
1/2 and open-label extension studies of lumasiran. Lumasiran has
received U.S. and EU Orphan Drug Designations, Breakthrough Therapy
Designation from the U.S. Food and Drug Administration (FDA), and a
Priority Medicines (PRIME) designation from the European Medicines
Agency (EMA). Full ILLUMINATE-A study results will be presented in
an oral plenary session on Tuesday, March 31, 2020 at OxalEurope
International Congress in Amsterdam, Netherlands.
The Company is also conducting ILLUMINATE-B – a global Phase 3
study of lumasiran in PH1 patients less than six years of age, with
results expected in mid-2020, and ILLUMINATE-C – a global Phase 3
study of lumasiran in PH1 patients of all ages with advanced renal
disease, with results expected in 2021.
Conference Call Information Alnylam Management will
discuss the ILLUMINATE-A results via conference call on Tuesday,
December 17, 2019 at 8:00 am ET. A webcast presentation will also
be available on the Investors page of the Company’s website,
www.alnylam.com. To access the call, please dial 800-239-9838
(domestic) or +1-323-794-2551 (international) five minutes prior to
the start time and refer to conference ID 6976021. A replay of the
call will be available beginning at 11:00 am ET on the day of the
call. To access the replay, please dial 888-203-1112 (domestic) or
+1-719-457-0820 (international) and refer to conference ID
6976021.
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 commercial RNAi therapeutic products are
ONPATTRO® (patisiran), approved in the U.S., EU, Canada, Japan, and
Switzerland, and GIVLAARI™ (givosiran), approved in the U.S.
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 implications of the positive topline results from
the ILLUMINATE-A study and the potential for lumasiran to have a
meaningful clinical impact on patients living with PH1, its plans
and expected timing for filing applications for regulatory approval
of lumasiran, its plans for reporting the full results from the
ILLUMINATE-A study, expectations regarding the timing for reporting
results from the ILLUMINATE-B and ILLUMINATE-C clinical studies,
and expectations regarding the potential to exceed its “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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191217005160/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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