Journey from Preclinical to FDA Approval: Patisiran and the Rise of Lipid Nanoparticle Drug Delivery
Faculty Mentor
Ahmed Abu Fayyad
Major/Area of Research
Pharmaceutical Sciences, Drug Delivery, Pharm.D.
Description
INTRODUCTION: Small interfering RNA (siRNA) can act as potent therapeutic agents in silencing genes. However, siRNA are inherently unstable and require a drug delivery platform to reach their intended target safely and effectively. Lipid nanoparticles (LNPs) have emerged as delivery systems in encapsulating RNA, improving their stability and cellular uptake. Patisiran became the first FDA-approved lipid nanoparticle formulation to be available for hereditary transthyretin-mediated (hATTR) amyloidosis. The objective of this review is to highlight milestones that led to Patisiran’s development from preclinical to FDA approval and the translatability of LNPs for cell-specific targets.
METHOD: A literature search was conducted, focusing on relevant studies published between 2015 and 2025, using key terms: Patisiran, transthyretin-mediated amyloidosis, drug delivery platform, siRNA, lipid nanoparticles, and lipid-polymer nanoparticles. This review looked across the preclinical and clinical stages of Patisiran’s development and how it opened a new avenue of siRNA therapeutics with the use of lipid nanoparticles as a delivery platform.
RESULTS: This literature review demonstrates Patisiran’s development and its utilization of LNPs as promising delivery platforms for siRNA. In-vitro studies confirmed successful knockdown of transthyretin (TTR) gene expression, meanwhile in-vivo studies further revealed the effectiveness of LNPs and their therapeutic potential. A study completed with mouse models exhibited greater than 95% TTR gene silencing and a study involving non-human primates study exhibited 85-96% TTR gene knockdown. Furthermore, data from the Phase II Open Label Extension (OLE) study and APOLLO Phase III studies provided evidence that long-term Patisiran treatment offered robust TTR knockdown, leading to significant clinical improvement and quality of life.
DISCUSSION/CONCLUSION: The FDA approval of Patisiran led to LNPs becoming clinically backed as viable drug delivery platforms for RNA therapeutics. This addressed challenges in intracellular delivery and RNA degradation are now used as a gold standard for the targeted delivery of siRNA towards specific cells beyond the liver.
Journey from Preclinical to FDA Approval: Patisiran and the Rise of Lipid Nanoparticle Drug Delivery
INTRODUCTION: Small interfering RNA (siRNA) can act as potent therapeutic agents in silencing genes. However, siRNA are inherently unstable and require a drug delivery platform to reach their intended target safely and effectively. Lipid nanoparticles (LNPs) have emerged as delivery systems in encapsulating RNA, improving their stability and cellular uptake. Patisiran became the first FDA-approved lipid nanoparticle formulation to be available for hereditary transthyretin-mediated (hATTR) amyloidosis. The objective of this review is to highlight milestones that led to Patisiran’s development from preclinical to FDA approval and the translatability of LNPs for cell-specific targets.
METHOD: A literature search was conducted, focusing on relevant studies published between 2015 and 2025, using key terms: Patisiran, transthyretin-mediated amyloidosis, drug delivery platform, siRNA, lipid nanoparticles, and lipid-polymer nanoparticles. This review looked across the preclinical and clinical stages of Patisiran’s development and how it opened a new avenue of siRNA therapeutics with the use of lipid nanoparticles as a delivery platform.
RESULTS: This literature review demonstrates Patisiran’s development and its utilization of LNPs as promising delivery platforms for siRNA. In-vitro studies confirmed successful knockdown of transthyretin (TTR) gene expression, meanwhile in-vivo studies further revealed the effectiveness of LNPs and their therapeutic potential. A study completed with mouse models exhibited greater than 95% TTR gene silencing and a study involving non-human primates study exhibited 85-96% TTR gene knockdown. Furthermore, data from the Phase II Open Label Extension (OLE) study and APOLLO Phase III studies provided evidence that long-term Patisiran treatment offered robust TTR knockdown, leading to significant clinical improvement and quality of life.
DISCUSSION/CONCLUSION: The FDA approval of Patisiran led to LNPs becoming clinically backed as viable drug delivery platforms for RNA therapeutics. This addressed challenges in intracellular delivery and RNA degradation are now used as a gold standard for the targeted delivery of siRNA towards specific cells beyond the liver.