10/29/2018
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`Press Announcements > FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease
`
`FDA News Release
`
`FDA approves first-of-its kind targeted
`RNA-based therapy to treat a rare disease
`
`First treatment for the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adult
`patients
`
`For Immediate Release
`
`August 10, 2018
`
`Release
`
`The U.S. Food and Drug Administration today approved Onpattro (patisiran) infusion for the treatment of peripheral
`nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients.
`This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and
`often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart
`and other organs. It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid
`(siRNA) treatment.
`
`“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. In this case, the effects of the disease cause a degeneration of the nerves, which can manifest in pain,
`weakness and loss of mobility,” said FDA Commissioner Scott Gottlieb, M.D. “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. We’re committed to advancing scientific principles that enable the efficient
`development and review of safe, effective and groundbreaking treatments that have the potential to change
`patients’ lives.”
`
`RNA acts as a messenger within the body’s cells, carrying instructions from DNA for controlling the synthesis of
`proteins. RNA interference is a process that occurs naturally within our cells to block how certain genes are
`expressed. Since its discovery in 1998, scientists have used RNA interference as a tool to investigate gene function
`and its involvement in health and disease. Researchers at the National Institutes of Health
`(https://www.nih.gov/news-events/news-releases/gene-silencing-study-finds-new-targets-parkinsons-
`disease), for example, have used robotic technologies to introduce siRNAs into human cells to individually turn off
`nearly 22,000 genes.
`
`This new class of drugs, called siRNAs, work by silencing a portion of RNA involved in causing the disease. More
`specifically, Onpattro encases the siRNA into a lipid nanoparticle to deliver the drug directly into the liver, in an
`infusion treatment, to alter or halt the production of disease-causing proteins.
`
`https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm616518.htm
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`PROTIVA - EXHIBIT 2024
`Moderna Therapeutics, Inc. v. Protiva Biotherapeautics, Inc.
`IPR2018-00739
`
`

`

`10/29/2018
`
`Press Announcements > FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease
`
`Affecting about 50,000 people worldwide, hATTR is a rare condition. It is characterized by the buildup of abnormal
`deposits of protein fibers called amyloid in the body's organs and tissues, interfering with their normal functioning.
`These protein deposits most frequently occur in the peripheral nervous system, which can result in a loss of
`sensation, pain, or immobility in the arms, legs, hands and feet. Amyloid deposits can also affect the functioning of
`the heart, kidneys, eyes and gastrointestinal tract. Treatment options have generally focused on symptom
`management.
`
`Onpattro is designed to interfere with RNA production of an abnormal form of the protein transthyretin (TTR). By
`preventing the production of TTR, the drug can help reduce the accumulation of amyloid deposits in peripheral
`nerves, improving symptoms and helping patients better manage the condition.
`
`“There has been a long-standing need for a treatment for hereditary transthyretin-mediated amyloidosis
`polyneuropathy. This unique targeted therapy offers these patients an innovative treatment for their symptoms that
`directly affects the underlying basis of this disease,” said Billy Dunn, M.D., director of the Division of Neurology
`Products in the FDA’s Center for Drug Evaluation and Research.
`
`The efficacy of Onpattro was shown in a clinical trial involving 225 patients, 148 of whom were randomly assigned
`to receive an Onpattro infusion once every three weeks for 18 months, and 77 of whom were randomly assigned to
`receive a placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on
`measures of polyneuropathy including muscle strength, sensation (pain, temperature, numbness), reflexes and
`autonomic symptoms (blood pressure, heart rate, digestion) compared to those receiving the placebo infusions.
`Onpattro-treated patients also scored better on assessments of walking, nutritional status and the ability to perform
`activities of daily living.
`
`The most common adverse reactions reported by patients treated with Onpattro are infusion-related reactions
`including flushing, back pain, nausea, abdominal pain, dyspnea (difficulty breathing) and headache. All patients
`who participated in the clinical trials received premedication with a corticosteroid, acetaminophen, and
`antihistamines (H1 and H2 blockers) to reduce the occurrence of infusion-related reactions. Patients may also
`experience vision problems including dry eyes, blurred vision and eye floaters (vitreous floaters). Onpattro leads to
`a decrease in serum vitamin A levels, so patients should take a daily Vitamin A supplement at the recommended
`daily allowance.
`
`The FDA granted this application Fast Track (/ForPatients/Approvals/Fast/ucm405399.htm), Priority Review
`(/ForPatients/Approvals/Fast/ucm405405.htm) and Breakthrough Therapy
`(/ForPatients/Approvals/Fast/ucm405397.htm) designations. Onpattro also received Orphan Drug
`(/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/de
`fault.htm) designation, which provides incentives to assist and encourage the development of drugs for rare
`diseases.
`
`Approval of Onpattro was granted to Alnylam Pharmaceuticals, Inc.
`
`The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by
`assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological
`products for human use, and medical devices. The agency also is responsible for the safety and security of our
`nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating
`tobacco products.
`
`###
`
`Inquiries
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`10/29/2018
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`Press Announcements > FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease
`
`Media
`
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`
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`  301-796-5349
`
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`
`Related Information
`
`Approved Drugs: Questions and Answers (/Drugs/ResourcesForYou/Consumers/ucm054420.htm)
`New Class of Drugs Fulfills Promise of RNA-based Medicine (/Drugs/NewsEvents/ucm615953.htm)
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