Wainua Receives FDA Approval as a Treatment for Hereditary ATTRv-PN

Wainua (eplontersen; AstraZeneca, Cambridge, UK; Ionis Pharmaceuticals, Carlsbad, CA) has been approved by the Food and Drug Administration (FDA) as a treatment for hereditary amyloid transthyretin amyloidosis polyneuropathy (ATTRv-PN) in adults. Wainua is a ligand-conjugated antisense (LICA) medication that inhibits the production of the transthyretin (TTR) protein and is administered by auto-injector.

The FDA approval is based on positive 35-week interim analysis data from the phase 3 NEURO-TTRansform clinical study (NCT04136184), with results published in The Journal of the American Medical Association (JAMA). NEURO-TTRansform was a global, open-label, randomized study evaluating the efficacy and safety of Wainua in 168 adult participants aged 18 to 82 years with a diagnosis of ATTRv-PN. Participants were randomly assigned 6:1 to receive either subcutaneous Wainua at 45 mg every 4 weeks, or subcutaneous Tegsedi (inotersen; Sobi, Waltham, MA) at 300 mg every week with a transition to Wainua at week 37. Results were compared to the historical placebo group from the earlier phase 3 NEURO-TTR clinical trial (NCT01737398). The study’s coprimary endpoints were serum TTR concentration and neuropathy impairment as measured by the modified Neuropathy Impairment Score +7 (mNIS+7), with a key secondary endpoint measuring quality of life according to the Norfolk Quality of Life Diabetic Neuropathy (Nofolk QoL-DN) total score. At week 65, the following results were reported:

• A difference of -70.4% in adjusted mean percentage reduction in serum TTR concentration (95% CI, -75.2% to -65.7%; P<.001)
• A difference of -24.8 in adjusted mean change improvement in mNIS+7 (95% CI, -31.0 to -18.6; P<.001)
• A difference of -19.7 in adjusted mean change in Norfolk QoL-DN total score (95% CI, -25.6 to -13.8; P<.001)

"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," said Michael J. Polydefkis, MD, Professor of Neurology at Johns Hopkins University School of Medicine and an investigator in the NEURO-TTRansform study. "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."

According to Ionis Pharmaceuticals, Wainua will be available in the US starting in January 2024. The medication was granted orphan drug designation (ODD) in the United States and European Union for investigation as a treatment for transthyretin-mediated amyloidosis (ATTR), and it is under evaluation as a treatment for transthyretin-mediated cardiomyopathy (ATTR-CM) in the phase 3 CARDIO-TTRansform (NCT04136171) clinical trial.