FDA Approves Eplontersen (Wainua) for ATTRv Polyneuropathy

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The FDA has approved eplontersen (Wainua) for treating polyneuropathy in adult patients with hereditary transthyretin-mediated amyloidosis, making it the only medication approved for self-administration via auto-injector pen for this condition.

The US Food and Drug Administration has approved eplontersen (Wainua) for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv polyneuropathy) in adult patients.

Announced on December 21, 2023, the approval, which was awarded to AstraZeneca and Ionis Pharmaceuticals, is based on positive 35-week data from the phase 3 NEURO-TTRansform and makes eplontersen the only approved medicine for the treatment of ATTRv polyneuropathy that can be self-administered via an auto-injector.1

“Many people living with hereditary transthyretin-mediated amyloid polyneuropathy are unable to fully enjoy their lives because of the relentless, progressive and debilitating effects of the disease. Approval of WAINUA represents a meaningful advancement in treatment, one that gives those who are living with transthyretin-mediated amyloid polyneuropathy help managing the disease,” said NEURO-TTRansform study investigator Michael J. Polydefkis, MD, Professor of Neurology at Johns Hopkins University School of Medicine.1

A 45 mg subcutaneous injection administered every 4 weeks, eplontersen a ligand-conjugated antisense oligonucleotide (LICA medicine designed to reduce the production of transthyretin and AstraZeneca expects it to be available in the US beginning in January 2024. The announcement of approval comes just less than 10 months after Ionis Pharmaceuticals announced the submission of a New Drug Application for the agent on March 7, 2023.1,2

The application for regulatory approval in the US was based on 35-week data from the aforementioned NEURO-TTRansform trial, which demonstrated treatment with eplontersen resulted in consistent and sustained benefit on the co-primary endpoints of serum transthyretin concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7) as well as a key secondary endpoint of quality of life on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN). An open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries, data from the trial demonstrating the effects out to 66 weeks were published in the Journal of the American Medical Association.1,2

With a population of 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented transthyretin variant. For the purpose of analysis, an inotersen trial with similar eligibility criteria and end points served as a historical placebo. The trial’s primary efficacy endpoints at were changes from baseline in serum transthyretin concentration, mNIS+7 composite score, and Norfolk QoL-DN total score.3

Full trial results suggested the adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4%; 95% Confidence Interval [CI], −75.2% to −65.7%; P < .001) at week 65. Further analysis suggested greater improvements in adjusted mean change from baseline to week 66 in the trial occurred among those receivingeplontersen relative to the historical placebo cohort for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8; 95% CI, −31.0 to −18.6; P < .001) and Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7; 95% CI, −25.6 to −13.8; P < .001).3

Safety analyses from the trial indicated 4% of the eplontersen group and 3% of the placebo group discontinued use before week 66 due to adverse events. Investigators noted there were no deaths in the placebo arm and there were 2 deaths among the eplontersen arm through week 66, which investigators purport is consistent with known disease-related sequelae.1

“The path to getting an accurate diagnosis can often be a long, arduous journey and it is critical that a timely and accurate diagnosis is made not only for the individual experiencing symptoms but for their families and loved ones,” said Isabelle Lousada, president and chief executive officer of the Amyloidosis Research Consortium.1 “It is exciting to see new innovations coming through and increased efforts to raise awareness in an area that has often been overlooked or neglected.”

Beyond the US, eplontersen is under regulatory review in Europe and other parts of the world. AstraZeneca also pointed out eplontersen is being examined for use as a treatment of transthyretin-mediated amyloid cardiomyopathy in the phase 3 CARDIO-TTRansform trial.1


  1. AstraZeneca. WAINUA (eplontersen) granted first-ever regulatory approval in the US for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis. AstraZeneca Press Releases. December 21, 2023. Accessed December 22, 2023.
  2. Ionis Pharmaceuticals, Inc. Ionis announces FDA acceptance of New Drug Application for Eplontersen for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). Ionis Pharmaceuticals, Inc. March 7, 2023. Accessed December 22, 2023.
  3. Coelho T, Marques W, Dasgupta NR, et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023;330(15):1448–1458. doi:10.1001/jama.2023.18688