Market Overview

Alnylam Completes Enrollment in ENVISION Phase 3 Study of Givosiran, an Investigational RNAi Therapeutic for the Treatment of Acute Hepatic Porphyrias (AHPs)


− Enrollment Completed Ahead of Schedule, Eight Months After First
Patient Randomized −

− Company Remains on Track to Report Interim Analysis Data by the End
of September and Full Study Data in Early 2019 −

Pharmaceuticals, Inc.
 (NASDAQ:ALNY), the leading RNAi therapeutics
company, today announced that it has achieved full patient accrual in
its ENVISION Phase 3 study of givosiran, an investigational RNAi
therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the
treatment of acute hepatic porphyrias (AHPs). Enrollment was completed
with 94 AHP patients randomized across 36 sites in 18 countries,
surpassing the initial target of approximately 75 patients due to high
patient demand.

The Company reiterated its previous guidance that it expects to report
topline results of the interim analysis by the end of September in
support of a potential accelerated approval, and topline results on the
primary endpoint of annualized attack rate after six months of treatment
in early 2019. The interim analysis is based on lowering of urinary
aminolevulinic acid (ALA) levels from approximately 30 patients at three
months of treatment as a surrogate biomarker that is reasonably likely
to predict clinical benefit. Pending Company and FDA review of the
program at the time of interim analysis and assuming positive results
and acceptable safety, the Company continues to expect to submit an NDA
at or around year-end 2018, seeking an accelerated approval.

"We're pleased to have completed enrollment in the ENVISION Phase 3
study, and we're thankful to the porphyria community for their support
in helping to raise awareness about the importance of clinical trials in
rare diseases," said Akin Akinc, Vice President and General Manager,
Givosiran Program at Alnylam. "The fact that we achieved this important
milestone significantly ahead of schedule – in addition to exceeding the
initial enrollment target – highlights the urgent demand and high unmet
need for novel therapies in this disease setting. We remain committed to
advancing givosiran, which we believe has the potential to transform the
treatment landscape for patients with AHPs."

The ENVISION Phase 3 trial is a randomized, double-blind,
placebo-controlled, global, multicenter study to evaluate the efficacy
and safety of givosiran in patients with a documented diagnosis of AHPs.
Patients were randomized on a 1:1 basis to receive 2.5 mg/kg of
givosiran or placebo subcutaneously administered monthly, over a 6-month
treatment period. The primary endpoint is the annualized rate of
porphyria attacks requiring hospitalization, urgent healthcare visit or
hemin administration at home over the 6-month treatment period. The
planned interim analysis will evaluate reduction of a urinary biomarker
– ALA – in approximately 30 patients after three months of dosing, as a
surrogate endpoint reasonably likely to predict clinical benefit. Key
secondary and exploratory endpoints will evaluate reductions in the
hallmark symptoms of AHPs, such as pain, nausea, and fatigue, as well as
impact on quality of life.

All patients completing the 6-month treatment period are eligible to
continue on an open-label extension (OLE) study in which they will
receive treatment with givosiran for up to 30 months.

In April, Alnylam presented new
results from the Phase 1 and Phase 1/2 open-label extension (OLE) studies

of givosiran for the treatment of AHPs during the European Association
for the Study of the Liver (EASL) Annual International Liver Congress in
Paris, France.

About Acute Hepatic Porphyrias
Acute hepatic porphyrias
(AHPs) are a family of rare, genetic diseases characterized by
potentially life-threatening attacks and for many patients chronic
debilitating symptoms that negatively impact daily functioning and
quality of life. AHPs are comprised of four subtypes, each resulting
from a genetic defect leading to deficiency in one of the enzymes of the
heme biosynthesis pathway in the liver: acute intermittent porphyria
(AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and
ALAD-deficiency porphyria (ADP). These defects cause the accumulation of
neurotoxic heme intermediates aminolevulinic acid (ALA) and
porphobilinogen (PBG), with ALA believed to be the primary neurotoxic
intermediate responsible for causing both attacks and ongoing symptoms
between attacks. Common symptoms of AHPs include severe, diffuse
abdominal pain, weakness, nausea, and fatigue. The symptoms of AHPs can
often resemble that of other more common conditions such as irritable
bowel syndrome, appendicitis, fibromyalgia, and endometriosis and
consequently, patients afflicted with AHPs are often misdiagnosed or
remain undiagnosed for up to 15 years. Currently, there are no
treatments approved to prevent debilitating attacks and treat the
chronic symptoms of the disease.

About Givosiran
Givosiran is an investigational,
subcutaneously administered RNAi therapeutic targeting aminolevulinic
acid synthase 1 (ALAS1) in development for the treatment of acute
hepatic porphyrias (AHPs). Monthly administration of givosiran has the
potential to significantly lower induced liver ALAS1 levels in a
sustained manner and thereby decrease neurotoxic heme intermediates,
aminolevulinic acid (ALA) and porphobilinogen (PBG) to near normal
levels. By reducing accumulation of these intermediates, givosiran has
the potential to prevent or significantly reduce the occurrence of
severe and life-threatening attacks, control chronic symptoms, and
decrease the burden of the disease. Givosiran utilizes Alnylam's
Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology, which
enables subcutaneous dosing with increased potency and durability and a
wide therapeutic index. Givosiran has been granted Breakthrough Therapy
designation by the U.S. Food and Drug Administration (FDA) and PRIME
designation by the European Medicines Agency (EMA). Givosiran has also
been granted orphan drug designations in both the U.S. and the EU for
the treatment of AHPs. The safety and efficacy of givosiran are
currently being investigated in the ENVISION Phase 3 clinical trial and
ongoing Phase 1/2 OLE study and have not been evaluated by the FDA, the
EMA or any other health authority.

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. RNAi therapeutics are a
new class of medicines that harness the natural biological process of
RNAi. 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 in
developing medicines to improve the care of patients with genetic and
other diseases.

About Alnylam
Alnylam (NASDAQ:ALNY) is leading the
translation of RNA interference (RNAi) into a whole new class of
innovative medicines with the potential to improve the lives of people
afflicted with rare genetic, cardio-metabolic, and hepatic infectious
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. ONPATTRO, available in
the U.S. for the treatment of the polyneuropathy of hereditary
transthyretin-mediated (hATTR) amyloidosis in adults, is Alnylam's first
U.S. FDA-approved RNAi therapeutic. Alnylam has a deep pipeline of
investigational medicines, including three 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 800 people
worldwide and is headquartered in Cambridge, MA. For more information
about our people, science and pipeline, please visit 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 potential for givosiran to meet unmet needs of AHP patients, a
planned interim analysis and potential NDA filing for givosiran if such
interim analysis is positive, ENVISION study completion, the timing of
regulatory filings, and expectations regarding 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, 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.

Givosiran has not been evaluated 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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