Eplontersen demonstrated sustained benefit in Phase III trial for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) through 66 weeks.- AstraZeneca + Ionis

At 66 weeks , patients treated with eplontersen continued to demonstrate a statistically significant and clinically meaningful change from baseline versus an external placebo group on the co-primary endpoints of modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression, and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN). The trial also met its third co-primary endpoint demonstrating a statistically significant reduction in serum TTR concentration versus an external placebo group. TTR reductions were consistent with those reported at week 35. Eplontersen continued to demonstrate a safety and tolerability profile consistent with that observed at 35 weeks.

Sami Khella, M.D., Chief, Department of Neurology, Penn Presbyterian Medical Center and Professor of Clinical Neurology, University of Pennsylvania School of Medicine, said: “The positive results from the 66-week analysis of the Phase III NEURO-TTRansform trial show that eplontersen provided consistent and sustained transthyretin protein reduction and that a substantial number of patients improved in measures of both neuropathy progression and quality of life. This builds on the favourable 35-week results, which first demonstrated eplontersen’s potential to significantly improve outcomes in this underserved population.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “These results further underscore eplontersen’s potential to be a best-in-class treatment across all forms of transthyretin-mediated amyloidosis, including polyneuropathy and cardiomyopathy which can lead to heart failure. With limited treatment options currently available, there is an urgent unmet medical need for new therapies and earlier, accurate diagnosis across the different types of this systemic, progressive and fatal condition.”

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. 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. Earlier this month, the FDA accepted a New Drug Application for eplontersen for the treatment of ATTRv-PN. Eplontersen was granted Orphan Drug Designation in the US.

Eplontersen is currently being evaluated in the Phase III CARDIO-TTRansform trial for transthyretin 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.

The results from both the 35 and 66-week analyses of the trial will be presented as an Emerging Science presentation at the American Academy of Neurology Annual Meeting in April.

NEURO-TTRansform :NEURO-TTRansform is a global, open-label, randomised trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN. The trial has enrolled adult patients with ATTRv-PN Stage 1 or Stage 2 and will be compared to the external placebo group from the Tegsedi (inotersen) NEURO-TTR registrational trial that Ionis completed in 2017. The final analysis comparing eplontersen to external placebo was completed at week 66 and all patients will be followed on treatment until week 85, when they will have the option to transition into an open-label extension study.The 66-week analysis evaluated percent change from baseline in serum TTR concentration, changes in the mNIS+7 and Norfolk-QOL-DN in the eplontersen group versus an external placebo group.The mNIS+7 uses highly standardised, quantitative and referenced assessments to quantify muscle weakness, muscle stretch reflexes, sensory loss and autonomic impairment. The Norfolk QoL-DN is a patient-reported questionnaire capturing neuropathy-related QoL.