AstraZeneca, Ionis announce eplontersen trial met all endpoints

Detailed results from the NEURO-TTRansform Phase III trial in patients with hereditary transthyretin-mediated amyloid polyneuropathy showed AstraZeneca (AZN) and Ionis’ eplontersen met all co-primary endpoints and secondary endpoints at 66 weeks versus an external placebo group. The positive results being presented in an Emerging Science Session at the American Academy of Neurology, or AAN, 2023 Annual Meeting in Boston, Massachusetts demonstrate that eplontersen’s efficacy, safety and administration profile may provide an important new option in this fatal disease with significant unmet need. At 66 weeks, patients treated with eplontersen demonstrated consistent and sustained benefit on the three co-primary endpoints of serum transthyretin, or TTR, concentration, neuropathy impairment and quality of life, or QoL. Eplontersen achieved a least squares mean reduction of 82% in TTR serum concentration from baseline, compared to an 11% reduction from baseline in the external placebo group. Eplontersen halted disease progression as measured by modified Neuropathy Impairment Score +7, or mNIS+7, resulting in a 0.28 point LS mean increase compared to a 25.06 point increase for the external placebo group from baseline. 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 also improved QoL demonstrating a 5.5 point LS mean decrease on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy, compared to a 14.2 point increase in the external placebo group (19.7 point LS mean improvement; pless than0.0001). 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. 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 also achieved statistically significant improvements in all secondary endpoints versus the external placebo group and continued to demonstrate a favorable safety and tolerability profile. The rate of treatment emergent adverse events in the eplontersen group was comparable or similar to the external placebo group across all major categories. There were no adverse events of special interest that led to study drug discontinuation.