Eplontersen Halted ATTRv-PN Disease Progression and Improved Neuropathy Impairment and Quality of Life in Study

Ionis Pharmaceuticals today announced that the Phase 3 NEURO-TTRansform study for AstraZeneca and Ionis’ eplontersen in patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) met all co-primary endpoints and secondary endpoints at 66 weeks versus an external placebo group. The positive results are being presented today in an Emerging Science Session at the American Academy of Neurology (AAN) 2023 Annual Meeting in Boston. ATTRv-PN is a debilitating disease driven by the progressive accumulation of TTR amyloid deposits, which causes progressive nerve damage and leads to organ failure and eventually death.

At 66 weeks, patients treated with eplontersen demonstrated consistent and sustained benefit on the three co-primary endpoints measuring serum transthyretin (TTR) concentration, neuropathy impairment and quality of life: Eplontersen achieved a least squares (LS) mean reduction of 82% in serum TTR concentration from baseline, compared to an 11% reduction from baseline in the external placebo group (p<0.0001). Eplontersen halted disease progression as measured by modified Neuropathy Impairment Score +7 (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 (24.8 point LS mean improvement; p<0.0001). 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.

“In the past, patients with hereditary transthyretin amyloid polyneuropathy usually deteriorated given the limited available treatments. This new study shows eplontersen can halt progression of neuropathy and improve quality of life at 66 weeks when compared to placebo,” said Sami Khella, M.D., chief, department of neurology at Penn Presbyterian Medical Center, professor of clinical neurology at the Perelman School of Medicine at the University of Pennsylvania School of Medicine and a principal investigator on the NEURO-TTRansform study. “Today’s important results demonstrate that eplontersen has a consistent and sustained treatment effect and reinforces its potential as an important medicine for the thousands of patients living with this debilitating and fatal disease.”

“In the NEURO-TTRansform study, we were encouraged to see a substantial number of patients treated with eplontersen improved in measures of neuropathy impairment and quality of life at both the interim and final analyses,” said Eugene Schneider, M.D., executive vice president and chief clinical development officer for Ionis. “We and our partners at AstraZeneca are especially grateful to the patients who participated in this study. With our potential approval in the U.S. in December and plans to file for regulatory approval in the EU and other countries, we are looking forward to potentially bringing eplontersen to ATTRv-PN patients in this largely underrecognized global patient population.”

As part of a global development and commercialization agreement, Ionis and AstraZeneca are seeking regulatory approval for eplontersen for the treatment of ATTRv-PN in the U.S. and plan to seek regulatory approval in Europe and other parts of the world. The U.S. Food and Drug Administration accepted the New Drug Application for eplontersen for the treatment of ATTRv-PN with a PDUFA action date of December 22, 2023. Eplontersen was granted Orphan Drug Designation in the U.S.

Eplontersen is currently being evaluated in the Phase 3 CARDIO-TTRansform study for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a systemic, progressive and fatal condition that typically leads to progressive heart failure and often death within three to five years from disease onset.