Market Overview

Alnylam Receives Positive CHMP Opinion for ONPATTRO™ (patisiran) for the Treatment of Hereditary Transthyretin-Mediated Amyloidosis in Adults with Stage 1 or Stage 2 Polyneuropathy


– European Commission Decision Expected in September –

– Recommended Summary of Product Characteristics (SmPC) Includes Data
on Secondary and Exploratory Endpoints, Including Results on Cardiac
Parameters –

Pharmaceuticals, Inc.
(NASDAQ:ALNY), the leading RNAi therapeutics
company, announced today that the Committee for Medicinal Products for
Human Use (CHMP) has adopted a Positive Opinion recommending marketing
authorization of patisiran for the treatment of hereditary
transthyretin-mediated amyloidosis (hATTR amyloidosis) in adults with
stage 1 or stage 2 polyneuropathy. If approved by the European
Commission (EC), the medicine will be commercialized under the brand

"We are delighted with this positive opinion, and today's recommendation
by the CHMP takes us one step closer to bringing RNAi therapeutics, an
entirely new class of innovative medicines, to patients around the
world," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam
Pharmaceuticals. "Our hope with patisiran is to transform the treatment
of hATTR amyloidosis for the patients living with this devastating

"hATTR amyloidosis is a progressively debilitating disease that often
impacts patients and their families in the prime of their lives," said
Theresa Heggie, Head of Europe, Alnylam Pharmaceuticals. "We are ready
to launch patisiran following the EC decision, and hope that it will
help to meet the pressing need for new treatment options for patients
living with hATTR amyloidosis in Europe."

The CHMP positive opinion is based on the evaluation of the effects of
patisiran in patients with hATTR amyloidosis and its safety profile as
demonstrated in the APOLLO Phase 3 study. The SmPC recommended by the
CHMP includes data from APOLLO primary and secondary endpoints, as well
as exploratory cardiac endpoints. The results of the APOLLO study were
published July 5, 2018 in The New England Journal of Medicine

The European Medicines Agency reviewed patisiran under the accelerated
assessment procedure that is granted to medicines that the CHMP believes
are of major interest for public health and therapeutic innovation. A
CHMP positive opinion is one of the final steps before marketing
authorization is granted by the European Commission. The European
Commission will now review the CHMP recommendation to deliver its final
decision, applicable to all 28 EU member states, plus Iceland,
Liechtenstein and Norway. Patisiran is currently under priority review
as a Breakthrough Therapy with the U.S. Food and Drug Administration
(FDA), with an action date of August 11, 2018. Regulatory filings in
other markets, including Japan, are planned for mid-2018.

In APOLLO, the safety and efficacy of patisiran
were evaluated in a diverse, global population of hATTR amyloidosis
patients. Patients were randomized in a 2:1 ratio to receive intravenous
patisiran (0.3 mg per kilogram of body weight) or placebo once every 3
weeks for 18 months. The study showed that patisiran improved measures
of polyneuropathy, quality of life, activities of daily living,
ambulation, nutritional status and autonomic symptoms relative to
placebo in adult patients with hATTR amyloidosis. The APOLLO study used
the modified Neuropathy Impairment Score +7 (mNIS+7) to assess motor
strength, reflexes, sensation, nerve conduction and postural blood

  • Patients treated with patisiran had a mean 6.0-point decrease
    (improvement) in mNIS+7 score from baseline compared to a 28.0-point
    mean increase (worsening) for patients in the placebo group, resulting
    in a 34.0-point mean difference relative to placebo, after 18 months
    of treatment.
  • While nearly all patisiran-treated patients experienced a treatment
    benefit relative to placebo, 56 percent of patisiran-treated patients
    experienced significant improvement in measures of their
    polyneuropathy (as assessed by mNIS+7 score) relative to their own
    baseline with 18 months of treatment, compared to four percent of
    patients who received placebo.
  • As measured by the Norfolk Quality of Life Diabetic Neuropathy
    (QoL-DN) Score, 51 percent of patients treated with patisiran
    experienced improvement in quality of life at 18 months relative to
    their own baseline, compared to 10 percent of the placebo-treated
  • Over 18 months of treatment, patients treated with patisiran
    experienced significant benefit vs. placebo for all other efficacy
    endpoints including measures of activities of daily living, walking
    ability, nutritional status, and autonomic symptoms.
  • Patisiran was associated with favorable effects on exploratory
    endpoints related to cardiac structure and function in patients with
    cardiac involvement.
  • The incidence and severity of adverse events were similar in patients
    receiving patisiran and placebo. The most common adverse events that
    occurred more frequently with patisiran than with placebo were
    peripheral edema and infusion-related reactions.

About Patisiran
Patisiran is an investigational,
intravenously administered RNAi therapeutic targeting transthyretin
(TTR) in development for the treatment of hereditary ATTR amyloidosis.
It is designed to target and silence specific messenger RNA, potentially
blocking the production of TTR protein before it is made. This may help
to reduce the deposition and facilitate the clearance of TTR amyloid in
peripheral tissues and potentially restore function to these tissues.

About hATTR Amyloidosis
Hereditary transthyretin
(TTR)-mediated amyloidosis (hATTR) is an inherited, progressively
debilitating, and often fatal disease caused by mutations in the TTR
gene. TTR protein is primarily produced in the liver and is normally a
carrier of vitamin A. Mutations in the TTR gene cause abnormal amyloid
proteins to accumulate and damage body organs and tissue, such as the
peripheral nerves and heart, resulting in intractable peripheral sensory
neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as
other disease manifestations. hATTR amyloidosis represents a major unmet
medical need with significant morbidity and mortality, affecting
approximately 50,000 people worldwide. The median survival is 4.7 years
following diagnosis, with a reduced survival (3.4 years) for patients
presenting with cardiomyopathy. In Europe, treatment options that can
modify the course of the disease are limited and there remains a
pressing need for novel medicines to help treat patients with hATTR

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 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, 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

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 transform 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 and deep pipeline of
investigational medicines, including four 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
in the U.S. and Europe 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 data supporting the CHMP positive opinion, recommended SmPC, and
ongoing regulatory reviews of patisiran, the potential implications of
such data for patients, the commercial readiness of Alnylam to launch
patisiran in Europe, 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, 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.

None of Alnylam's investigational therapeutics have 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 such investigational

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