Gene-silencing Therapy (RNAi) is on the Move

Published on October 11th, 2018

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“The recent announcements by Alnylam Pharmaceuticals and Arrowhead Pharmaceuticals are excellent news for our patients. Both companies are developing therapies for the liver by ‘silencing’ the production of the alpha-1 antitrypsin protein in the liver. Alnylam just filed some CTA with the United Kingdom authorities to conduct a Phase 1/2 trial while Arrowhead announced that it has completed dosing healthy volunteers in its Alpha-1 trial,” said Jean-Marc Quach, president and CEO of The Alpha-1 Project (TAP).

Alnylam Pharmaceuticals announced that it has submitted a Clinical Trial Authorization (CTA) application to the Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase 1/2 study of ALN-AAT02 in the United Kingdom, an investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of Alpha-1 Antitrypsin Deficiency (Alpha-1) associated liver disease (Alpha-1 liver disease).

ALN-AAT02 is an investigational, subcutaneously administered RNAi therapeutic targeting alpha-1 antitrypsin (AAT) in development for the treatment of AAT deficiency-associated liver disease (Alpha-1 liver disease). ALN-AAT02 utilizes Alnylam’s enhanced stabilization chemistry plus (ESC+)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of ALN-AAT02 have not been evaluated by the FDA, EMA or any other health authority.

Also, Arrowhead recently announced that it has completed enrollment of its Phase 1 clinical trial of ARO-AAT, their second generation subcutaneously administered RNAi therapeutic that is being developed as a treatment for liver disease associated with Alpha-1, while last August, Alnylam’s Onpattro (patisiran) received the first U.S. approval for an RNAi drug, an infusion for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients, which uses the same delivery platform as the Alpha-1 products by both companies.

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 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.

These developments, approvals and advancements, affirm the gene-silencing class of drugs as a new frontier in the field of medicine. and the Alpha-1 Foundation

Sources: Alnylam Pharmaceuticals and the Alpha-1 Foundation

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