Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Alnylam Reports Positive Phase II Data for ALN-TTR02, an RNAi Therapeutic

Published: Monday, July 01, 2013
Last Updated: Monday, July 01, 2013
Bookmark and Share
Interim results in ATTR patients show up to 93% knockdown of TTR with activity toward both wild-type and mutant TTR.

Alnylam Pharmaceuticals, Inc. announced the achievement of positive clinical results from its Phase II trial of ALN-TTR02, an RNAi therapeutic targeting the transthyretin (TTR) gene for the treatment of TTR-mediated amyloidosis (ATTR). The data were presented today at the 2013 Biennial Meeting of the Peripheral Nerve Society, held June 29 – July 3 in St. Malo, France. Interim results show that multiple doses of ALN-TTR02 led to robust and statistically significant (p<0.001) knockdown of serum TTR protein levels of up to 93%. Knockdown of TTR, the disease-causing protein in ATTR, was found to be rapid, dose dependent, and durable, and similar activity was observed toward both wild-type and mutant protein. In addition, ALN-TTR02 was found to be generally safe and well tolerated in this study.

“These new ALN-TTR02 results are a major milestone in our TTR program, where – for the first time in ATTR patients – we have demonstrated robust knockdown of up to 93% of circulating wild-type and mutant TTR in a multi-dose study. The clinical relevance of lowering circulating TTR has been demonstrated in ATTR patients who have benefited from the elimination of mutant TTR through liver transplantation. In addition, we are very encouraged with the continued safety profile of ALN-TTR02 which has now been extended with this experience in ATTR patients and with multi-dose regimens,” said Jared Gollob, M.D., Vice President, Clinical Research at Alnylam. “This Phase II trial continues in patients receiving a once-every-three-week dosing regimen and we plan to share the complete data set at the International Symposium on Familial Amyloidotic Polyneuropathy in Rio de Janeiro this November.”

“I am very encouraged by these new clinical activity and safety data with ALN-TTR02, an RNAi therapeutic for the treatment of ATTR. Specifically, I am impressed with the potent, rapid, and durable knockdown of both mutant and wild-type TTR, which is important since TTR protein reduction in patients with ATTR has the potential to delay or even reverse disease progression with associated clinical benefits,” said Professor David Adams, M.D., Ph.D., Neurology Department Head at CHU de Bicetre (APHP), Le Kremlin-Bicetre Cedex, France. “I very much look forward to the continued advancement of RNAi therapeutics in clinical trials for the treatment of ATTR, as there are currently few options for patients suffering from this debilitating, progressive disease.”

The Phase II trial with ALN-TTR02 is an open-label, multi-center, multi-dose, dose-escalation trial to evaluate the safety and tolerability of two doses of ALN-TTR02 and to demonstrate clinical activity based on serial measurement of circulating serum levels of wild-type and mutant TTR. The study was designed to treat up to 30 ATTR polyneuropathy patients with ALN-TTR02 administered at doses of 0.01 to 0.30 mg/kg, using either a once-every-four-week or once-every-three-week dosing regimen. To date, 25 patients in eight cohorts have been dosed in the study, and all patients for the final cohort have been scheduled for dosing. The international study is being conducted at 10 sites in Portugal, France, Sweden, Germany, Spain, Brazil, and the U.S.

Data from the first 19 patients enrolled and analyzed in this study showed that multiple doses of ALN-TTR02 resulted in rapid, dose-dependent, and durable knockdown of serum TTR levels. As compared with the lowest dose group of 0.01 mg/kg, there was a statistically significant knockdown of serum TTR at doses of 0.15 mg/kg (p<0.01) and 0.30 mg/kg (p<0.001). At 0.30 mg/kg administered once every four weeks, mean TTR knockdown at nadir of 82.6% and 84.8% was observed following the first and second doses, respectively, and maximum TTR knockdown was up to 90.8%. At 0.30 mg/kg administered once every three weeks, mean TTR knockdown at nadir of 83.1% and 87.4% was observed following the first and second doses, respectively, and maximum TTR knockdown was up to 92.8%.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Alnylam Advances New Innovations in RNAi Therapeutics
Alnylam Pharmaceuticals, Inc. has announced advancement of innovations in RNAi therapeutics with presentation of scientific data on two new platform technologies.
Tuesday, October 20, 2015
Alnylam Receives Notice of Allowance from USPTO
Allowed claims of Manoharan '478 application cover GalNAc-conjugates independent of length, sequence, and disease target.
Saturday, July 26, 2014
Alnylam Reports Positive Phase II Data for Patisiran (ALN-TTR02)
New results in ATTR patients show up to 96% knockdown of TTR with activity toward both wild-type and mutant TTR.
Tuesday, November 12, 2013
Alnylam and Collaborators Publish Results from Phase I Clinical Trial with RNAi Therapeutic
Results published in Cancer Discovery document most comprehensive human experience to date for RNAi therapeutics delivered with lipid nanoparticles (LNPs).
Thursday, January 31, 2013
Alnylam and PBL Sign License Agreement for Baulcombe & Hamilton RNAi Patent
PBL has granted Alnylam a world-wide, non-exclusive license to the Baulcombe patent for use in the field of human therapeutics.
Thursday, May 24, 2012
Alnylam and Arrowhead Form Collaboration and Licensing Agreement
Alnylam has granted Arrowhead a license under its intellectual property that enables the discovery, development, and commercialization of an RNAi therapeutic targeting the hepatitis B virus (HBV).
Thursday, January 05, 2012
Alnylam Reports Positive Preliminary Clinical Results for RNAi Therapeutic
The company achieved positive preliminary results from its ongoing clinical trial of ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of severe hypercholesterolemia. ALN-PCS demonstrated statistically significant RNAi silencing of PCSK9 of up to 66% and reductions of up to over 50% in levels of low-density lipoprotein cholesterol (LDL-C), a clinically validated endpoint.
Wednesday, January 04, 2012
Alnylam and MIT Collaborators Discover Novel “Core-Shell” Nanoparticles for Systemic Delivery of RNAi Therapeutics
Development of novel nanoparticles that have optimal chemical and physical properties for effective intracellular delivery of RNAi therapeutics.
Tuesday, July 26, 2011
Alnylam, MIT Team Up for 'Binary' Approach to Delivering siRNA
New data describes new approach for systemic delivery of RNAi therapeutics using combinations of lipid-like materials called "lipidoids.”
Monday, July 25, 2011
Alnylam Biotherapeutics Presents Data on new Applications of RNAi Technology for Biologics Manufacturing
siRNAs targeting vesivirus potently block CHO cell infection, highlighting uses of RNAi technologies to prevent or treat viral infections in bioprocessing.
Friday, November 19, 2010
Alnylam Grants new InterfeRx™ Intellectual Property License to Tekmira
Agreement aims to develop and commercialize of TKM-Ebola, an RNAi therapeutic for the treatment of Ebola Virus Infection.
Monday, November 08, 2010
Alnylam and Collaborators Publish new Pre-clinical Research on Therapeutic Silencing of Parkinson's Disease Gene
New Research shows silencing of alpha-synuclein in the Substantia Nigra of non-human primates with an RNAi therapeutic.
Tuesday, August 31, 2010
Alnylam and Collaborators Discover Key Mechanism for Delivery of RNAi Therapeutics
Data Reveals an endogenous targeting mechanism for systemic delivery of RNAi therapeutics to liver using lipid nanoparticles.
Monday, January 11, 2010
Alnylam and Collaborators at MIT Report New Pre-clinical Research on Systemic Delivery of RNAi Therapeutics
Findings published in PNAS highlight discovery of novel “Lipidoids,” lipid-like materials, for low dose in vivo gene silencing.
Wednesday, December 30, 2009
Alnylam Presents Pre-Clinical Data on ALN-TTR for the Treatment of Transthyretin-Mediated Amyloidosis
New data demonstrate durable in vivo efficacy for ALN-TTR at the 60th Annual Meeting of the American Association for the Study of Liver Diseases.
Tuesday, November 03, 2009
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos