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Food and Drug Administration (FDA) approves patisiran (Onpattro™): America’s first RNA-based therapy

By: Michael Lim, PharmD Candidate c/o 2020

           In the investigation of gene function and its role in health care and disease management, RNA interference is an important scientific tool. Possessing the ability to individually turn off nearly 22,000 genes upon introduction into human cells, small interfering ribonucleic acids (siRNAs), while useful in research settings, have been difficult to translate into robust therapies.1,2 In August 2018, the Food and Drug Administration (FDA), approved patisiran (Onpattro™), an siRNA treatment. It is the first treatment type in the United States that combats disease by silencing the genetic components driving it and represents a new class of drugs.1,2

Patisiran is an infusion approved for the treatment of peripheral nerve disease due to hereditary transthyretin-mediated amyloidosis (hATTR), a rare condition in adults affecting fewer than 5,000 people in the United States and 50,000 people globally.1,2 In hATTR, abnormal deposits of amyloid protein fibers accumulate in organs and tissues. This interferes with their normal functioning. While deposits may appear in a variety of organs, including the heart, kidneys, and eyes, deposition occurs most frequently in the peripheral nervous system. This may manifest as loss of sensation, pain, or immobility in the hands, legs, arms, and feet.2

In contrast with prior treatments which prioritized symptomatic management, patisiran targets the source of the disease by silencing a disease-causing portion of RNA that produces an abnormal form of transthyretin (TTR) protein. When injected, patisiran delivers an enveloped siRNA in a lipid nanoparticle for infusion to the liver, where the silencing subsequently leads to the alteration or cessation of disease-causing protein production. By impeding the creation of abnormal TTR, patisiran can assist in the management of hATTR by reducing the accumulation of amyloid deposits in peripheral nerves and thereby improving symptoms.2 

Patisiran demonstrated its efficacy in a clinical trial involving 225 patients. One treatment arm of 148 patients received patisiran infusions once every three weeks for eighteen months while the other arm of 77 patients received placebo infusions at the same frequency. The patients receiving patisiran revealed better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms compared to the placebo group. Furthermore, better scores on assessments of walking, nutritional status, and ability to perform activities of daily living were found in the patisiran treatment arm.2

The recommended dosage of patisiran in patients weighing less than 100 kg is 0.3 mg/kg. Patients weighing more than 100 kg are recommended a dosage of 30 mg. Patisiran may cause infusion-related reactions (IRRs), so monitoring for signs and symptoms such as flushing and arthralgia is recommended. Furthermore, to reduce the risk of IRRs, it is required that patients receive premedication at least one hour prior to the start of patisiran infusion. These premedications include an intravenous corticosteroid such as dexamethasone 10 mg, oral acetaminophen 500 mg, an intravenous H1 blocker such as diphenhydramine 50 mg, and an intravenous H2 blocker such as ranitidine 50 mg. Pharmacists can promote safe medication use by ensuring that these agents or their oral equivalents are dispensed prior to patisiran infusions. In addition, patisiran may reduce serum vitamin A levels, therefore, patients are advised to supplement with the recommended daily allowance of vitamin A throughout the duration of therapy. If ocular symptoms such as night blindness are suggestive of vitamin A deficiency, referral to an ophthalmologist is merited.3

Patisiran’s manufacturer, Alnylam Pharmaceuticals, estimates that the cost of the drug for the average patient would be four hundred and fifty thousand dollars annually or three hundred and forty-five thousand dollars after rebates. However, Alnylam also stated that via agreements with health insurers, including Harvard Pilgrim Health Care, a portion of the cost would be refunded to patients who do not have sufficient health benefits.1

With its origin rooted in Dr. Andrew Fire and Dr. Craig Mello’s 2006 Nobel Prize winning RNA interference research in physiology and medicine, patisiran represents not only a significant achievement in the realm of pharmacotherapy but also genetic technology.4 Currently, RNA interference shows the most promise in rare disease states based in liver cells which absorb large-molecule drugs, such as those used to target RNA, more easily than the rest of the body.1 Furthermore, according to Dr. Mello, investigator at Howard Hughes Medical Institute and Professor at the University of Massachusetts Medical School, optimism is justified for the future development of RNA interference drugs in the treatment of other diseases.1  From the pharmacy perspective, patisiran represents a new option in the therapeutic management of hATTR and pharmacists can play a role in ensuring its proper dosing and safe usage. To conclude, FDA Commissioner Scott Gottlieb, M.D. commented, “This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms… New technologies like RNA inhibitors, that alter the genetic drivers of a disease, have the potential to transform medicine, so we can better confront and even cure debilitating illnesses.”2


  1. Loftus, P. New kind of drug, silencing genes, gets FDA approval; alnylam’s onpattro, approved to treat a rare nerve disorder, features the latest technology for fighting disease. Wall Street Journal (Online). Published 08/10/18. https://www.wsj.com/articles/fda-approves-first-drug-based-on-gene-silencing-research-1533923359. Accessed 08/31/18.
  2. Food and Drug Administration. FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease. U.S. Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616518.htm Published 08/10/18. Accessed 08/31/18.
  3. Onpattro™ (Patisiran) [package insert]. Cambridge, MA; Alnylam Pharmaceuticals Inc.; Revised 08/10/2018.
  4. The Nobel Prize in Physiology or Medicine 2006. The Nobel Prize. https://www.nobelprize.org/prizes/medicine/2006/summary/. Published 10/02/06. Accessed 08/31/18.
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