Profile
General Information
Wainua (eplontersen) is a transthyretin-directed antisense oligonucleotide.
Wainua is specifically indicated for the treatment of the polyneuropathy of hereditary transthyretin mediated amyloidosis in adults.
Dosing/Administration
- Wainua is supplied as a solution for subcutaneous injection.
- The recommended dosage is 45 mg administered by subcutaneous injection once monthly.
- Missed Dose: Administer Wainua as soon as possible after a missed dose. Resume dosing at monthly intervals from the date of the most recently administered dose.
Mechanism of Action
Wainua (eplontersen) is an antisense oligonucleotide-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.
Side Effects
Adverse effects associated with the use of Wainua may include, but are not limited to, the following:
- vitamin A decreased
- vomiting
Clinical Trial Results
The FDA approval of Wainua was based on positive 35-week interim analysis from the NEURO-TTRansform Phase 3 trial.
The trial enrolled adult patients with ATTRv-PN Stage 1 or Stage 2 compared to the external placebo group from the Teggsedi (inotersen) NEURO-TTR registrational trial that Ionis completed in 2017. The comparison of efficacy and safety for Wainua
versus external placebo was based on data up to week 66, and all patients were followed on treatment until week 85, when they had the option to transition into an open-label extension study
In the NEURO-TTRansform Phase III trial, patients treated with eplontersen demonstrated consistent and sustained benefit on the three co-primary endpoints of serum transthyretin (TTR) concentration, neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7) and quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).
Eplontersen achieved a least squares (LS) mean reduction of 82% in TTR serum concentration from baseline at 65 weeks, compared to an 11% reduction from baseline in the external placebo group.
Eplontersen demonstrated statistically significant benefits on both mNIS+7 and Norfolk QoL-DN at 35 weeks versus the external placebo group, which were further improved at 66 weeks. Eplontersen halted disease progression by mNIS+7, resulting in a 0.3 point LS mean increase at week 66 compared to a 25.1 point increase for the external placebo group from baseline (24.8 point LS mean improvement; p<0.001). Overall, 47% of treated patients showed improvements in neuropathy at 66 weeks compared to baseline versus 17% in the external placebo group. Among study completers, 53% of treated patients showed improvements in neuropathy at 66 weeks compared to baseline versus 19% in the external placebo group.
Eplontersen improved QoL (on Norfolk QoL-DN) demonstrating a 5.5 point LS mean decrease at 66 weeks (improvement), compared to a 14.2 point increase (worsening) in the external placebo group (19.7 point LS mean improvement; p<0.001).1 Overall, 58% of treated patients showed improvements in QoL at 66 weeks compared to baseline versus 20% in the external placebo group. Among study completers, 65% of treated patients showed improvements in QoL at 66 weeks compared to baseline versus 23% in the external placebo group.