Dicerna Announces FDA Clearance of Investigational New Drug (IND) Application for DCR-AUD for the Treatment of Alcohol Use Disorder
Jul 29, 2021
– Novel ALDH2-Targeting GalXC™ RNAi Candidate Designed to Address a Highly Prevalent and Undertreated Disorder1 –
– Dicerna Expects to Initiate Phase 1 Clinical Trial of DCR-AUD in the Third Quarter of 2021 –
AUD is a medical condition characterized by the inability to stop or control alcohol use despite social, occupational or health consequences.2 Aldehyde dehydrogenase 2, or ALDH2, is an enzyme that plays a key role in metabolizing alcohol. DCR-AUD has been shown to induce long-lasting liver-specific ALDH2 messenger RNA (mRNA) knockdown in nonclinical studies. By silencing ALDH2 in the liver and interrupting the alcohol metabolic pathway, DCR-AUD has the potential to induce real-time physiological feedback to help individuals seeking treatment for AUD regain control over harmful levels of alcohol use.
“The key to developing a successful treatment for the more than 14 million people affected by AUD is finding a way to help individuals regain control over their alcohol use,” said
Dicerna plans to initiate a 24-week, randomized, double-blind, placebo-controlled Phase 1 trial in the third quarter of 2021 to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of single-ascending doses of DCR-AUD in healthy volunteers. The trial will also assess the interaction between DCR-AUD treatment and alcohol consumption using standardized Ethanol Interaction Assessments.
About Alcohol Use Disorder (AUD)
Alcohol use disorder, or AUD, is a chronic disorder characterized by the inability to stop or control alcohol use despite social, occupational or health consequences. AUD presents as a problematic pattern of alcohol use leading to clinically significant impairment or distress. Symptoms can include compulsive drinking, loss of control over alcohol use and negative emotions when not drinking.2 AUD is one of the most common psychiatric disorders, affecting more than 14 million adults in the
DCR-AUD is Dicerna’s GalXC™ RNAi investigational candidate designed to silence ALDH2 (aldehyde dehydrogenase 2) messenger RNA (mRNA) expression in the liver. DCR-AUD has been shown to induce long-lasting liver-specific ALDH2 mRNA knockdown in nonclinical studies. Some individuals are born with naturally occurring mutations in one or both gene copies that encode the ALDH2 enzyme. In these people with ALDH2 mutations, alcohol consumption can result in uncomfortable physiological effects that occur soon after drinking. These effects are thought to be the reason people with ALDH2 mutations are much less likely to be affected by AUD. Dicerna designed DCR-AUD based on human genetic data that suggest knocking down ALDH2 mRNA in individuals with AUD may provide similar physiological feedback that is protective against harmful levels of alcohol consumption. Preclinical research for DCR-AUD was supported by a grant from the
About RNAi and Dicerna’s GalXC™ RNAi Platform Technologies
Ribonucleic acid interference, or RNAi, provides a unique advantage to other disease inhibitor technologies, like small-molecule pharmaceuticals or monoclonal antibodies. Instead of targeting proteins after they have been produced and released, RNAi silences the genes themselves via the specific destruction of the messenger RNA (mRNA) made from the gene. Rather than seeking to inhibit a protein, the RNAi approach can prevent a disease-causing protein’s creation, directly impacting disease manifestation.
Dicerna’s proprietary GalXC™ RNAi platform aims to advance the development of next-generation RNAi-based therapies. Investigational therapeutics developed using our flagship GalXC technology utilize a proprietary N-acetyl-D-galactosamine (GalNAc)-mediated structure of double-stranded RNA molecules that are designed to bind specifically to receptors on liver cells, leading to selective hepatocyte internalization and access to the RNAi machinery within the cells. Dicerna is continuously innovating and exploring new applications of RNAi technology beyond GalNAc-mediated delivery to the liver, including alternative RNA structures and fully synthetic ligands that target other tissues and enable new therapeutic applications, referred to as GalXC-Plus™.
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Examples of forward-looking statements include, among others, statements we make regarding the potential of DCR-AUD for the treatment of alcohol use disorder; market size for people affected by AUD; and timing of initiating a Phase 1 clinical trial of DCR-AUD in healthy volunteers. The process by which investigational therapies could potentially lead to an approved product is long and subject to highly significant risks. Applicable risks and uncertainties include those relating to Dicerna’s clinical research and other risks identified under the heading "Risk Factors" included in the Company’s most recent filings on Forms 10-K and 10-Q and in other future filings with the
4.Grant et al., JAMA Psychiatry 2015.
GalXC™ and GalXC-Plus™ are trademarks of