EPR Podcast 20 – RNAi Therapeutics – Paul Nioi, Alnylam Pharmaceuticals

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RNA interference (RNAi) medicines that can ‘silence’ or turn off the production of specific genes that cause or contribute to disease, are one of the exciting emerging modalities in drug development today.

In this episode, EPR Editor Caroline Peachey catches up with Dr Paul Nioi, Vice President of Discovery and Translational Research at Alnylam Pharmaceuticals to explore clinical development and manufacturing of RNAi medicines for large patient populations.

History and evolution of RNAi

Paul Nioi, Vice President of Discovery and Translational Research at Alnylam Pharmaceuticals

Founded in 2002, Alnylam Pharmaceuticals is developing around a dozen investigational RNAi therapeutics, in the areas of genetic medicines, cardio-metabolic diseases, infectious diseases, and central nervous system/ocular diseases.

Paul reflects on the evolution of RNAi therapeutics in the pharmaceutical landscape. Initially, few companies were working on RNAi, but interest and activity have grown significantly, with both startups and established pharmaceutical companies now exploring its potential, Paul explains.

The technology has primarily focused on rare diseases, but there is growing momentum to apply RNAi to more common conditions.

“When we began on this journey, there was a very, very solid focus on rare disease,” Paul says.

In contrast, today you can see “a crop of medicines for more common conditions [like hypertension and Type 2 diabetes] starting to come through the pipeline.”` Since this podcast was recorded Alnylam and Roche have agreed to jointly develop and commercialise an RNAi therapeutic as a treatment for hypertension. 

Benefits and challenges of developing RNAi medicines

The main benefit of RNAi medicines is their ability to target potentially any gene in the genome, including targets that are “undruggable” by small molecules and antibodies, explains Paul. The duration of action can extend from six to 12 months with a single subcutaneous injection.

“We hope this translates into better outcomes because you have consistency in silencing the gene as opposed to taking the pill one day, forgetting the next,” Paul says.

One major challenge discussed is the delivery of RNAi therapeutics to specific cells and tissues. The liver has been a successful target due to its involvement in various diseases, but expanding delivery to other tissues remains a challenge. Different approaches have been explored, including encapsulating RNA in lipid nanoparticles for intravenous delivery and modifying nucleotides to enhance stability and enable targeting to specific cells, notes Paul.

Looking ahead, Paul envisions advances in delivery methods to target a wider range of tissues, making RNAi medicines more routine in clinical practice and the emergence of related technologies like gene editing and mRNA delivery.

Listen now to this exclusive podcast to learn more!