Patisiran Continues to Demonstrate Reversal of
Neuropathy Progression, Improvement in Quality of Life, and
Consistent Safety Profile with Additional 24 Months of Treatment in
Global Open-Label Extension (OLE) Study
Interim Data Presented on Patisiran Treatment
in Patients with Disease Progression After an Orthotopic Liver
Transplant
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi
therapeutics company, today presented new results from the Global
Open-Label Extension (OLE) study of ONPATTRO® (patisiran), an RNAi
therapeutic for the treatment of the polyneuropathy of hereditary
ATTR (hATTR) amyloidosis in adults, at the European Academy of
Neurology (EAN) Virtual Congress. In addition, interim results were
presented from a Phase 3b trial evaluating treatment with patisiran
in patients with hATTR amyloidosis with disease progression after
receiving an orthotopic liver transplant (post-OLT).
“In collaboration with our clinical investigators, we are
pleased to have the opportunity to share data from our patisiran
clinical program in two abstracts at this year’s EAN virtual
conference. In particular, results from our Global OLE study
demonstrate sustained benefit for patients with hATTR amyloidosis
with polyneuropathy treated with ONPATTRO, with maintained
improvement in polyneuropathy symptoms and quality of life after an
additional 24 months of treatment. As of March 2020, thirteen
patients who rolled onto the Global OLE study have received
ONPATTRO for more than six years, the longest-running clinical
experience with an RNAi therapeutic,” said Eric Green, SVP and
General Manager of the TTR Program. “In addition, the interim
post-OLT data demonstrated robust TTR knockdown in this very high
unmet need population and point to the breadth of patients that may
benefit from treatment with ONPATTRO.”
Updated Results from Global OLE Study
24-month interim results were presented from the ongoing Global
OLE study of patisiran evaluating the drug’s long-term efficacy and
safety in eligible patients (N=211) who completed the Phase 2 OLE
(N=25) and APOLLO Phase 3 (N=186) studies. The data shared include
178 patients who had 24 months or greater of exposure as of an
October 7, 2019 cutoff date. Reductions in serum TTR levels were
maintained in patisiran-treated patients with continued dosing in
the Global OLE study. Patients on treatment for 42 months
demonstrated sustained improvement in neuropathy impairment and
quality of life relative to APOLLO study baseline, as shown by mean
negative changes in modified Neuropathy Impairment Score + 7
(mNIS+7) and Norfolk Quality of Life – Diabetic Neuropathy (QOL-DN)
scores. Patients on treatment from the Phase 2 OLE population also
demonstrated an improvement in mNIS+7 score over 48 months.
For APOLLO placebo patients subsequently treated with patisiran
for 24 months in the OLE study, neuropathy progression was also
notably halted and QOL improved. However, these patients had
experienced rapid progression while on placebo in the APOLLO study
and did not return to their baseline scores, highlighting the
importance of patients starting treatment with patisiran early.
The long-term safety profile of patisiran was consistent with
that observed and previously reported in the APOLLO Phase 3 study
and the Phase 2 OLE study.
ONPATTRO in Patients with Disease Progression Post-Orthotopic
Liver Transplant
In addition, data were presented from an interim analysis of the
Phase 3b open-label study conducted across several European
countries to evaluate the safety, efficacy and pharmacokinetics
(PK) of patisiran in patients with hATTR amyloidosis with disease
progression after receiving an orthotopic liver transplant (OLT).
Historically, OLT has been used to slow disease progression in
patients with early stages of hATTR amyloidosis; however, some
patients experience disease progression after the transplant due to
continued amyloid deposition of wild-type TTR on top of existing
amyloid deposits in tissues.
Twenty-three patients who showed disease progression post-OLT
(based on an increase in polyneuropathy disability [PND] score)
received patisiran infusion (0.3 mg/kg) every three weeks. After 3
weeks of patisiran treatment, the mean reduction from baseline in
serum TTR levels was 81.9 percent. At the time of interim safety
analysis (data cutoff as of December 9, 2019), the safety profile
of patisiran in this Phase 3b study was consistent with that
observed and previously reported in the APOLLO Phase 3 study. The
safety, efficacy, and PK of patisiran treatment post-OLT will be
further investigated in this ongoing study.
To view the data presented at EAN, please visit
www.alnylam.com/capella.
ONPATTRO (patisiran) lipid complex injection Important
Safety Information
Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in patients
treated with ONPATTRO. In a controlled clinical study, 19 percent
of ONPATTRO-treated patients experienced IRRs, compared to 9
percent of placebo-treated patients. The most common symptoms of
IRRs with ONPATTRO were flushing, back pain, nausea, abdominal
pain, dyspnea, and headache.
To reduce the risk of IRRs, patients should receive
premedication with a corticosteroid, acetaminophen, and
antihistamines (H1 and H2 blockers) at least 60 minutes prior to
ONPATTRO infusion. Monitor patients during the infusion for signs
and symptoms of IRRs. If an IRR occurs, consider slowing or
interrupting the infusion and instituting medical management as
clinically indicated. If the infusion is interrupted, consider
resuming at a slower infusion rate only if symptoms have resolved.
In the case of a serious or life-threatening IRR, the infusion
should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and
Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A
levels. Supplementation at the recommended daily allowance (RDA) of
vitamin A is advised for patients taking ONPATTRO. Higher doses
than the RDA should not be given to try to achieve normal serum
vitamin A levels during treatment with ONPATTRO, as serum levels do
not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they
develop ocular symptoms suggestive of vitamin A deficiency (e.g.
night blindness).
Adverse Reactions
The most common adverse reactions that occurred in patients
treated with ONPATTRO were upper respiratory-tract infections (29
percent) and infusion-related reactions (19 percent).
For additional information about ONPATTRO, please see the full
Prescribing Information.
About the Apollo Phase 3 Study
The APOLLO Phase 3 trial was a randomized, double-blind,
placebo-controlled, global study designed to evaluate the efficacy
and safety of patisiran in hATTR amyloidosis patients with
polyneuropathy. The primary endpoint of the study was the change
from baseline in modified Neuropathy Impairment Score +7 (mNIS+7)
relative to placebo at 18 months. Secondary endpoints included: the
Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score;
NIS-weakness (NIS-W); Rasch-built Overall Disability Scale (R-ODS);
timed 10-meter walk (10-MWT); modified BMI (mBMI); and the
composite autonomic symptom score-31 (COMPASS-31). In addition,
exploratory cardiac assessments included measurement of N-terminal
pro-brain natriuretic peptide (NT-ProBNP) levels and
echocardiography. The trial enrolled 225 hATTR amyloidosis patients
from 19 countries with 39 genotypes who were randomized 2:1,
patisiran:placebo, with patisiran administered at 0.3 mg/kg once
every three weeks for 18 months. All patients who completed the
APOLLO Phase 3 study were eligible to screen for the Global OLE
study, in which they have the opportunity to receive patisiran on
an ongoing basis.
About ONPATTRO® (patisiran)
ONPATTRO is an RNAi therapeutic that was approved in the United
States and Canada for the treatment of the polyneuropathy of hATTR
amyloidosis in adults. ONPATTRO is also approved in the European
Union, Switzerland and Brazil for the treatment of hATTR
amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and
in Japan for the treatment of hATTR amyloidosis with
polyneuropathy. ONPATTRO is an intravenously administered RNAi
therapeutic targeting transthyretin (TTR). It is designed to target
and silence TTR messenger RNA, thereby blocking the production of
TTR protein before it is made. ONPATTRO blocks the production of
TTR in the liver, reducing its accumulation in the body’s tissues
in order to halt or slow down the progression of the polyneuropathy
associated with the disease. For more information about ONPATTRO,
visit ONPATTRO.com.
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-motor 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.
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 RNAi therapeutics platform. Alnylam’s commercial RNAi
therapeutic products are ONPATTRO® (patisiran), approved in the
U.S., EU, Canada, Japan, Switzerland and Brazil, and GIVLAARI®
(givosiran), approved in the U.S. and 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. 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, including, without
limitation, Alnylam's views and plans with respect to the potential
for RNAi therapeutics, including patisiran’s ability to reverse
neuropathy progression and improve quality of life, its
expectations regarding the important role patisiran can play for
patients living with hATTR amyloidosis with polyneuropathy, the
potential for patisiran as a treatment in patients with disease
progression after an orthotopic liver transplant, and expectations
regarding the achievement of 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: the direct or indirect impact of the
COVID-19 global pandemic or a future pandemic, such as the scope
and duration of the outbreak, government actions and restrictive
measures implemented in response, material delays in diagnoses of
rare diseases, initiation or continuation of treatment for diseases
addressed by Alnylam products, or in patient enrollment in clinical
trials, potential supply chain disruptions, and other potential
impacts to Alnylam’s business, the effectiveness or timeliness of
steps taken by Alnylam to mitigate the impact of the pandemic, and
Alnylam’s ability to execute business continuity plans to address
disruptions caused by the COVID-19 or a future pandemic; Alnylam's
ability to discover and develop novel drug candidates and delivery
approaches and successfully demonstrate the efficacy and safety of
its product candidates, including patisiran; 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 or its marketed products, including
ONPATTRO, GIVLAARI, inclisiran, lumasiran and vutrisiran;
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 inclisiran, 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 achieving net product revenues for ONPATTRO within its
revised 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 reduced ranges
of guidance provided by Alnylam through the implementation of
further discipline in operations to moderate spend and its ability
to achieve a self-sustainable financial profile in the future
without the need for future equity financing; Alnylam’s ability to
establish and maintain strategic business alliances and new
business initiatives, including completing an agreement for funding
by Blackstone of certain R&D activities for vutrisiran and
ALN-AGT; Alnylam's dependence on third parties, including
Regeneron, for development, manufacture and distribution of certain
products, including eye and CNS products, Ironwood, for assistance
with the education about and promotion of GIVLAARI, and Vir for the
development of ALN-COV and other potential RNAi therapeutics
targeting SARS-CoV-2 and host factors for SARS-CoV-2; 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20200522005276/en/
Alnylam Pharmaceuticals, Inc. Christine Regan Lindenboom
(Investors and Media)
617-682-4340 Josh Brodsky
(Investors) 617-551-8276
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