Alnylam Presents New Long-Term Results from Global Open-Label Extension Study of ONPATTRO® (patisiran) at the European Academy of Neurology Virtual Congress 2020

May 22, 2020 16:30 UTC


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


CAMBRIDGE, Mass.--(BUSINESS WIRE)-- 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

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

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 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.


Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors and Media)

Josh Brodsky


Source: Alnylam Pharmaceuticals, Inc.

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