- Dicerna to Lead Global Clinical Development
and U.S. Commercialization of its DCR-A1AT and Alnylam’s ALN-AAT02
Investigational Therapeutics for the Treatment of Alpha-1 Liver
Disease; Alnylam Retains Post-Phase 3 Opt-in Right for Ex-U.S.
Commercialization -
- Companies Complete Non-Exclusive Intellectual
Property Cross-License Agreement for the Development and
Commercialization of Alnylam’s Lumasiran and Dicerna’s Nedosiran
Investigational Programs for Primary Hyperoxaluria -
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), and Dicerna
Pharmaceuticals, Inc. (Nasdaq: DRNA), both leaders in the field of
ribonucleic acid interference (RNAi) therapeutics, announced today
the formation of a development and commercialization collaboration
on investigational RNAi therapeutics for the treatment of alpha-1
antitrypsin (A1AT) deficiency-associated liver disease (alpha-1
liver disease). In addition, the companies have completed a
cross-license of their respective intellectual property for
Alnylam’s lumasiran and Dicerna’s nedosiran investigational
programs for the treatment of primary hyperoxaluria (PH). These
agreements will enhance and accelerate Alnylam’s and Dicerna’s
ability to bring these orphan product candidates to market.
“We are excited to bring our two leading RNAi therapeutics
companies together in our efforts to advance potentially
transformative medicines for the treatment of two rare diseases
with significant unmet medical need. Specifically, the new
agreements allow for Alnylam and Dicerna to join forces in areas of
common interest, namely alpha-1 liver disease and primary
hyperoxaluria,” said John Maraganore, Ph.D., Chief Executive
Officer of Alnylam. “We look forward to collaborating with Dicerna
to advance treatments for patients living with alpha-1 liver
disease, where Dicerna will lead development and U.S.
commercialization while Alnylam retains an ex-U.S.
commercialization option, where the company already has the
resources and experience to hit the ground running. Moreover, our
cross-license agreement for primary hyperoxaluria puts the needs of
patients and the patient community first, and ensures freedom to
operate for both companies for their respective RNAi therapeutic
programs in this ultra-rare orphan disease.”
“These agreements between Alnylam and Dicerna represent
biopharma collaboration at its best, unifying the strengths of two
leaders in RNAi innovation to rally behind the common goal of
delivering much-needed new therapies to patients with rare
diseases,” said Douglas M. Fambrough, Ph.D., President and Chief
Executive Officer of Dicerna. “By joining our efforts in alpha-1
liver disease, we believe we can be more strongly assured of
bringing forward the therapy with the greatest potential to benefit
patients. At the same time, our agreement related to lumasiran and
nedosiran clears a path for each company to offer a new and
differentiated treatment to patients with PH.”
Under the development and commercialization agreement, Alnylam’s
ALN-AAT02 and Dicerna’s DCR-A1AT, investigational RNAi
therapeutics, each in Phase 1/2 development, will be explored for
the treatment of alpha-1 liver disease. Under the agreement,
Dicerna assumes responsibility for both ALN-AAT02 and DCR-A1AT at
its cost, and may progress one or both of these investigational
medicines through clinical development. Dicerna will select which
product candidate(s) to advance in development for the treatment of
patients with alpha-1 liver disease. At the completion of Phase 3,
Alnylam has the no-cost opportunity to opt-in to commercialize the
selected candidate in countries outside the U.S., where it already
has a commercialization infrastructure in place. If Alnylam
exercises its opt-in right, each party shall pay tiered royalties
to the other party based on net product sales generated in its
territory at rates dependent on which candidate is commercialized.
In the event Alnylam waives its commercialization option, Dicerna
will retain worldwide rights to commercialize the selected
candidate(s) in exchange for milestones and royalties payable to
Alnylam, also at a rate dependent on which candidate is ultimately
commercialized.
In a separate agreement, Alnylam and Dicerna granted each other
a non-exclusive cross-license to their respective intellectual
property related to their PH treatment investigational programs to
ensure that each party has the freedom to develop and commercialize
its respective product candidate: Alnylam’s lumasiran targeting
glycolate oxidase (GO) for the treatment of PH type 1 and Dicerna’s
nedosiran targeting lactate dehydrogenase A (LDHA) for the
treatment of PH types 1, 2, and 3. Alnylam’s lumasiran has achieved
positive Phase 3 results in the ILLUMINATE-A study and is currently
the subject of a rolling new drug application (NDA) with the U.S.
Food and Drug Administration (FDA). Dicerna’s nedosiran is
currently being evaluated in the PHYOX™ clinical development
program in patients with PH. The cross-license agreement provides
for Alnylam to pay mid- to high-single-digit royalties to Dicerna
based on global net sales of lumasiran and for Dicerna to pay
low-single-digit royalties to Alnylam on global net sales of
nedosiran.
The transaction related to alpha-1 liver disease is subject to
the expiration or termination of the waiting period under the
Hart-Scott-Rodino Antitrust Improvements Act of 1976 and other
customary conditions.
About ALN-AAT02 and DCR-A1AT
ALN-AAT02 and DCR-A1AT are investigational, subcutaneously
administered RNAi therapeutics targeting alpha-1 antitrypsin (A1AT)
in development for the treatment of A1AT deficiency-associated
liver disease (alpha-1 liver disease). ALN-AAT02 utilizes Alnylam's
enhanced stabilization chemistry plus (ESC+)-GalNAc-conjugate
technology, which enables subcutaneous dosing with increased
selectivity and a wide therapeutic index. DCR-A1AT utilizes
Dicerna’s GalXCTM technology, which enables subcutaneous delivery
and optimizes the activity of the RNAi pathway so that it operates
in the most specific and potent fashion. The safety and efficacy of
ALN-AAT02 and DCR-A1AT have not been evaluated by the FDA, EMA or
any other health authority.
About Alpha-1 Antitrypsin Deficiency-Associated Liver
Disease
Alpha-1 antitrypsin (A1AT) deficiency is an autosomal disorder
that results in disease of the lungs and liver. A1AT is a
liver-produced serine proteinase inhibitor with the primary
function of protecting the lungs from neutrophil elastase and other
irritants that cause inflammation. About 95 percent of people with
A1AT deficiency are homozygous and carry two copies of the abnormal
Z allele (PiZZ) which expresses the Z-AAT protein. In the liver,
misfolding of the mutant Z-AAT protein hinders its normal release
into the blood thereby causing it to aggregate in hepatocytes,
leading to liver injury, fibrosis, cirrhosis, and hepatocellular
carcinoma (HCC). There are estimated to be approximately 120,000
individuals with the PiZZ mutation in the U.S. and major European
countries, and of these, 10 percent or more have an associated
liver pathology (alpha-1 liver disease) caused by the aggregates of
the misfolded Z-AAT protein. The only treatment options presently
available for alpha-1 liver disease patients are supportive care
and, in the case of advanced cirrhosis, liver transplantation.
RNAi-mediated inhibition of A1AT in people with alpha-1 liver
disease may represent a promising new way to treat this rare
disease.
About Lumasiran
Lumasiran is an investigational, subcutaneously administered
RNAi therapeutic targeting glycolate oxidase (GO), in development
for the treatment of primary hyperoxaluria type 1 (PH1), an
ultra-rare life threatening disease. GO is encoded by the
hydroxyacid oxidase 1 (HAO1) gene. 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 quarterly
subcutaneous maintenance 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 and pediatric rare disease 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 Nedosiran
Nedosiran (formerly referred to as DCR-PHXC) is the only RNAi
drug candidate in development for primary hyperoxaluria (PH) types
1, 2 and 3 and is Dicerna’s most advanced product candidate
utilizing the proprietary GalXC™ RNAi technology platform.
Nedosiran is designed to inhibit the lactate dehydrogenase A (LDHA)
enzyme – an enzyme that catalyzes the final step in a common
pathway resulting in oxalate overproduction in patients with PH1,
PH2 and PH3. Dicerna is evaluating the safety and efficacy of
nedosiran in patients with all known forms of PH as part of its
PHYOX clinical development program.
About Primary Hyperoxaluria (PH)
PH is an ultra-rare disease with three known types (PH1, PH2 and
PH3), each resulting from a mutation in one of three different
genes. In patients with PH, 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, especially in patients with PH1
and PH2, 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 minority of patients are fully responsive to Vitamin B6
therapy, there are no approved pharmaceutical therapies for PH.
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 and Dicerna’s RNAi therapeutic
platforms, 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 RNAi therapeutics platform. Alnylam’s commercial RNAi
therapeutic products are ONPATTRO® (patisiran), approved in the
U.S., EU, Canada, Japan, Brazil, and Switzerland, and GIVLAARI®
(givosiran), approved in the U.S and the EU. Alnylam has a deep
pipeline of investigational medicines, including six product
candidates that are in late-stage development. Alnylam is executing
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 is
headquartered in Cambridge, MA.
About Dicerna Pharmaceuticals, Inc.
Dicerna Pharmaceuticals, Inc. (Nasdaq: DRNA) is a
biopharmaceutical company focused on discovering, developing and
commercializing medicines that are designed to leverage ribonucleic
acid interference (RNAi) to selectively silence genes that cause or
contribute to disease. Using our proprietary RNAi technology
platform, GalXC™, Dicerna is committed to developing RNAi-based
therapies with the potential to treat both rare and more prevalent
diseases. By reducing the level of disease-causing proteins in the
hepatocytes of the liver, Dicerna’s GalXC platform has the
potential to safely target conditions that are difficult to treat
with other modalities. Continually innovating, Dicerna is also
exploring new applications of RNAi technology beyond the liver,
targeting additional tissues and enabling new therapeutic
applications. In addition to our own pipeline of core discovery and
clinical candidates, Dicerna has established collaborative
relationships with some of the world’s leading pharmaceutical
companies, including Novo Nordisk A/S, Roche, Eli Lilly and
Company, Alexion Pharmaceuticals, Inc. and Boehringer Ingelheim
International GmbH. Between Dicerna and our collaborative partners,
we currently have more than 20 active discovery, preclinical or
clinical programs focused on rare, cardiometabolic,
viral-infectious, chronic-liver and complement-mediated diseases,
as well as neurodegeneration and pain. At Dicerna, our mission is
to interfere – to silence genes, to fight disease, to restore
heath. For more information, please visit www.dicerna.com.
Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future
expectations, plans and prospects, including, without limitation,
Alnylam's views and plans with respect to the potential for RNAi
therapeutics, including ALN-AAT02, lumasiran, DCR-A1AT and
nedosiran, the development and potential commercialization of
ALN-AAT02 and/or DCR-A1AT and its potential to opt-in to such
program(s) in the future to commercialize outside of the U.S.,
expectations regarding the rolling submission of an NDA for
lumasiran and the potential benefit of lumasiran and nedosiran for
patients with PH, and expectations regarding the continued
execution on 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: potential risks to Alnylam’s business, activities and
prospects as a result of the COVID-19 pandemic, or delays or
interruptions resulting therefrom; Alnylam's ability to discover
and develop novel drug candidates; its ability to successfully
demonstrate the efficacy and safety of its product candidates,
including ALN-AAT02; the pre-clinical and clinical results for its
product candidates, including ALN-AAT02, 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 or its marketed products, including
ALN-AAT02 or lumasiran; obtaining, maintaining and protecting
intellectual property; intellectual property matters including
potential patent litigation relating to its platform, products or
product candidates; obtaining regulatory approval for its product
candidates, including lumasiran, and maintaining regulatory
approval and obtaining pricing and reimbursement for its products,
including ONPATTRO and GIVLAARI; progress in continuing to
establish a commercial and ex-United States infrastructure;
successfully launching, marketing and selling its approved products
globally, including ONPATTRO and GIVLAARI, and achieve net product
revenues for ONPATTRO within its expected range during 2020;
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
within the ranges of its expected guidance and achieve a
self-sustainable financial profile in the future, 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, including Vir, for
development of candidates for the treatment of infectious diseases,
including COVID-19, and commercialization of any infectious disease
product resulting therefrom, Regeneron, for development,
manufacture and distribution of certain products, including eye and
CNS products, and Ironwood, for assistance with the education about
and promotion of GIVLAARI in the U.S.; 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 Annual Report on Form 10-K 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.
Dicerna Forward-Looking Statements
Various statements in this release concerning Dicerna’s future
expectations, plans and prospects, including, without limitation,
Dicerna's views and plans with respect to the potential for RNAi
therapeutics, including ALN-AAT02, DCR-A1AT and nedosiran, the
development and potential commercialization of ALN-AAT02 and/or
DCR-A1AT and the opportunity to accelerate development for
patients, expectations regarding future royalties earned from sales
of lumasiran or from commercialization of ALN-AAT02 and/or DCR-A1AT
outside the United States, expectations regarding the rolling
submission of an NDA for lumasiran and the potential benefit of
lumasiran and nedosiran for patients with PH and the success of
Dicerna’s PHYOX clinical program and expectations regarding the
success of the collaboration with Alnylam, 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: potential risks to Dicerna’s
business, activities and prospects as a result of the COVID-19
pandemic, or delays or interruptions resulting therefrom; Dicerna’s
ability to discover and develop novel drug candidates; its ability
to successfully demonstrate the efficacy and safety of its product
candidates, including nedosiran, DCR-A1AT and/or ALN-AAT02; the
preclinical and clinical results for its product candidates,
including nedosiran, DCR-A1AT and/or ALN-AAT02, 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 preclinical and/or clinical testing;
delays, interruptions or failures in the manufacture and supply of
its product candidates, including nedosiran, DCR-A1AT or ALN-AAT02;
obtaining, maintaining and protecting intellectual property,
Dicerna’s dependence on existing collaborators and success of
future collaborations, as well as those risks more fully discussed
in the “Risk Factors” filed with Dicerna’s most recent Annual
Report on Form 10-K filed with the Securities and Exchange
Commission (SEC) and in other filings that Dicerna makes with the
SEC. In addition, any forward-looking statements represent
Dicerna’s views only as of today and should not be relied upon as
representing its views as of any subsequent date. Dicerna
explicitly disclaims any obligation, except to the extent required
by law, to update any forward-looking statements.
GalXC™ and PHYOX™ are trademarks of Dicerna Pharmaceuticals,
Inc.
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Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom (Investors and Media)
+1-617-682-4340
Josh Brodsky (Investors) +1-617-551-8276
Dicerna Pharmaceuticals, Inc.
Media: Amy Trevvett, Dicerna Pharmaceuticals, Inc. +1
617-612-6253 atrevvett@dicerna.com
Investors: Lauren Stival, Stern Investor Relations, Inc. +1
212-362-1200 lauren.stival@sternir.com
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