OnpattroEdit
Onpattro is the brand name for patisiran, a pioneering RNA interference therapy used to treat hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis). Developed by Alnylam Pharmaceuticals and approved for adults with polyneuropathy caused by hATTR amyloidosis, it represents a landmark in precision medicine by directly lowering the liver’s production of transthyretin, the protein responsible for the disease’s toxic amyloid deposits. As the first approved small interfering RNA (RNA interference) therapy, Onpattro helped move rare-disease treatment into a new era of targeted, mechanism-based intervention. In clinical practice, the medicine is delivered as an intravenous infusion every three weeks and aims to halt or slow the progression of debilitating neuropathy and autonomic symptoms associated with the disease, improving quality of life for affected patients. The therapy has also prompted ongoing discussions about access, pricing, and the role of innovation incentives in rare-disease care Orphan drug systems.
hATTR amyloidosis is a progressive, often fatal disorder in which misfolded transthyretin accumulates as amyloid deposits in nerves and organs. Until the advent of patisiran, treatment largely focused on managing symptoms, with limited ability to address the underlying proteinopathy. By suppressing hepatic production of transthyretin, Onpattro targets the root cause of amyloid buildup in many patients, offering a disease-modifying option that can change the trajectory of polyneuropathy and related autonomic complications. The drug’s development and approval are frequently cited in discussions about how modern biotechnology can transform outcomes for patients with rare, genetically defined conditions. For background on the protein involved, see transthyretin and amyloidosis; for the disease subtype focused on heritable forms, see hereditary transthyretin-mediated amyloidosis.
Medical use
Indication: Onpattro is indicated for adults with hereditary transthyretin-mediated amyloidosis presenting with polyneuropathy, with or without autonomic neuropathy. The aim is to slow or halt neurologic progression and to improve patient function and daily living. See the official labeling for specifics and exclusions. See also APOLLO trial for pivotal clinical evidence supporting these outcomes.
Administration: The drug is given as an intravenous infusion approximately every three weeks, under supervision that allows monitoring for infusion-related reactions. Premedication and monitoring may be used in practice to minimize adverse infusion events. See intravenous infusion and infusion-related reaction for general notes on administration and safety.
Population and cautions: Onpattro is studied in adults; use in pediatric patients is not indicated by the standard labeling. Clinicians evaluate hepatic and renal function, potential drug interactions, and baseline neurologic status when determining suitability. For mechanistic context, see RNA interference.
Mechanism of action
Patisiran is a small interfering RNA designed to silence the mRNA that encodes transthyretin in hepatic cells. Delivered in a lipid nanoparticle formulation that enables uptake by liver tissue, patisiran reduces the synthesis of transthyretin, thereby decreasing circulating and tissue-associated amyloid deposition. By addressing the source of the problem rather than only its symptoms, Onpattro aims to change the disease course in patients with hATTR amyloidosis. See transthyretin and lipid nanoparticle for related topics; see RNA interference for the broader technology context.
Development and regulatory history
Discovery and development: Patisiran was developed to exploit the gene-silencing capability of RNA interference in a way that targets transthyretin production in the liver. The development program emphasized delivering the therapeutic payload specifically to hepatic tissue, leveraging a lipid nanoparticle carrier.
Regulatory milestones: Onpattro received regulatory approval in the United States in 2018 and subsequently in other major jurisdictions, reflecting a landmark moment for RNAi therapeutics and for regulatory pathways recognizing mechanism-based therapies for rare diseases. Approvals were supported by data from the APOLLO trial, a pivotal study demonstrating meaningful neurological benefit and a favorable risk profile in adults with hATTR amyloidosis-related polyneuropathy. See also FDA and European Medicines Agency for regulatory context.
Intellectual property and market context: As with other novel biologics and targeted therapies, Onpattro’s development benefited from Orphan drug incentives and intellectual property protections that help sustain the expensive, high-risk process of bringing a rare-disease therapy to market. See discussions of drug pricing and intellectual property for broader policy context, and note how these elements interact with access programs and payer decisions.
Clinical evidence and safety
Efficacy: In the APOLLO trial, patisiran demonstrated statistically significant and clinically meaningful improvements in measures of neuropathy and quality of life compared with control. These results supported the continued approval and use of Onpattro in eligible adults with hATTR amyloidosis and polyneuropathy. See APOLLO trial for details.
Safety: Common adverse events include infusion-related reactions, peripheral edema, gastrointestinal symptoms, and mild laboratory abnormalities. As with many therapies that modulate protein expression, clinicians monitor liver function and other organ systems during treatment. See infusion-related reaction and liver function test for related safety topics.
Comparative landscape: Onpattro was the first approved RNAi therapy, paving the way for subsequent gene-silencing medicines such as Amvuttra (vutrisiran) and other RNAi-based approaches. See Amvuttra for a later development in the same therapeutic approach.
Economic and policy considerations
From a market-informed perspective, the Onpattro program underscores the tradeoffs involved in funding breakthrough therapies for rare diseases. High development costs, small patient populations, and the value of extending meaningful life can justify substantial upfront prices within a framework that relies on patient access through private plans and public payers. Proponents argue that robust intellectual property protections and orphan-drug incentives are necessary to sustain long-run innovation in areas with high uncertainty and uncertain markets. Critics contend that drug pricing for ultra-rare diseases can place heavy burdens on patients and payers, provoking calls for price negotiation or value-based pricing arrangements. In the right balance, many argue that encouraging innovation—while expanding access through assistance programs and responsible payer strategies—best serves patients with the most unmet medical needs. Debates about these policies often reflect broader disagreements about how to reconcile pharmaceutical innovation with affordability; anti-innovation critiques are viewed by supporters as overstated in their assessment of risk and impact on patient access. See drug pricing, Orphan drug policy, and Medicare/private health insurance dynamics for related discussion.