FDA Approves Patisiran Infusion for Polyneuropathy in hATTR


The approval is a first of its kind for the rare disease, and the first in a new class of drugs—small interfering ribonucleic acid (siRNA) treatments.

Dr Scott Gottlieb

FDA Commissioner Scott Gottlieb, MD

Scott Gottlieb, MD

The FDA announced an approval of patisiran (Onpattro) infusion for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients.

The approval is a first of its kind for the rare disease. It is also the first FDA approval of a new class of drugs—small interfering ribonucleic acid (siRNA) treatments, according to the agency.

“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, MD, in a statement.1 “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.”

The therapy, designed to interfere with RNA production of abnormal TTR, was developed by Alnylam. Its approval was granted based on the APOLLO phase III clinical trial, which included 225 patients with hATTR amyloidosis, randomizing them 2:1 to either patisiran (n = 148) or placebo (n = 77). Data from the APOLLO trial was presented at the 2018 Peripheral Nerve Society (PNS) Annual Meeting, in Baltimore, Maryland.

The study’s primary endpoint, change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7), showed a greater reduction in mNIS+7 and was consistently associated with a higher probability that a patient will have improved or stabilized ambulatory status in patisiran-treated patients (P <.0001). Additionally, patients with a mNIS+7 change of <0 after 18 months were revealed to have greater chances of improving or stabilizing ambulatory status compared to those with mNIS+7 scores ≥0 (P <.0001).

Following 18 months of treatment, a greater proportion of those given patisiran showed stable or improved familial amyloid polyneuropathy (FAP) Stage (79% compared to 44%) and polyneuropathy disability (PND) score (73% compared to 30%) compared to placebo. Only patients receiving patisiran experienced FAP Stage and PND improvements. Observed changes in FAP Stage (P = 9.5 x 108) and PND (P = 1.3 x 1010) score were statistically significant. At 9 and 18 months, neuropathy progression relative to baseline was seen with a least squares (LS) mean increase in mNIS+7 of 14.0 and 28.0 points, respectively, for patients randomized to placebo.

Overall health status, assessed using the EuroQOL-5-dimension 5-level (EQ-5D-5L), was shown to be preserved or improved from baseline in all domains for the patisiran group. In mobility, 70% of the patisiran group compared to 22% of the placebo group; in self-care, 66% compared to 21%; in usual activities, 72% compared to 25%; in pain/discomfort, 73% compared to 31%; and in anxiety/depression, 81% compared to 45%. The EuroQOL visual analog scale showed an improvement of 2.4 points for those administered patisiran compared to a -7.1 decline in placebo patients, a 9.5-point difference (P <.001).

“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, MD, the director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.

Additionally, on July 27, 2018, Alnylam received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), recommending the marketing authorization of the therapy in Europe.2

“We are delighted with this positive opinion, and today’s recommendation by the CHMP takes us one step closer to bringing RNAi therapeutics, an entirely new class of innovative medicines, to patients around the world,” John Maraganore, PhD, the chief executive officer of Alnylam Pharmaceuticals, said at the time.


1. FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease [press release]. Bethesda, MD: FDA; August 10, 2018. fda.gov/NewsEvents/Newsroom/PressAnnouncements/UCM616518.htm. Accessed August 10, 2018.

2. Alnylam Presents New Analyses of Clinical Results from APOLLO Phase 3 Study of Patisiran at 2018 Peripheral Nerve Society Annual Meeting [press release]. Cambridge, MA: Alnylam Pharmaceuticals; July 23, 2018. alnylam.com/news-releases/news-release-details/alnylam-presents-new-analyses-clinical-results-apollo-phase-3. Accessed August 10, 2018.

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