Washington – Detailed results from the NEURO-TTRansform Phase III trial in patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) showed AstraZeneca and Ionis’ eplontersen met all co-primary endpoints and secondary endpoints at 66 weeks versus an external placebo group.1
The positive results being presented today in an Emerging Science Session at the American Academy of Neurology (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.1
At 66 weeks, patients treated with eplontersen demonstrated consistent and sustained benefit on the three co-primary endpoints of serum transthyretin (TTR) concentration, neuropathy impairment and quality of life (QoL). Eplontersen achieved a least squares (LS) mean reduction of 82% in TTR serum concentration from baseline, compared to an 11% reduction from baseline in the external placebo group (p<0.0001).1
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. Eplontersen also improved QoL demonstrating a 5.5 point LS mean decrease (improvement) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), compared to a 14.2 point increase (worsening) in the external placebo group (19.7 point LS mean improvement; p<0.0001). 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.1
Eplontersen also achieved statistically significant improvements in all secondary endpoints versus the external placebo group and continued to demonstrate a favourable 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.1
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 trial, said: “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. 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.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Without treatment, hereditary transthyretin-mediated amyloid polyneuropathy is a relentlessly progressive disease. These results show that eplontersen sustains reduced transthyretin levels and improves neuropathy progression and quality of life consistently across a substantial number of patients. We are confident in eplontersen’s potential to be a much needed and differentiated treatment option for patients living with all types of this devastating disease, which can also lead to heart failure.”
ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.2
As part of a global development and commercialisation agreement, AstraZeneca and Ionis are seeking regulatory approval for eplontersen for the treatment of ATTRv-PN in the US and plan to seek regulatory approval in Europe and other parts of the world.3 Last month, the US Food and Drug Administration accepted a New Drug Application for eplontersen for the treatment of ATTRv-PN.3 Eplontersen was granted Orphan Drug Designation in the US.3
Eplontersen is currently being evaluated in the CARDIO-TTRansform Phase III trial for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM),4 a systemic, progressive and fatal condition that typically leads to progressive heart failure and often death within three to five years from disease onset.