Topline results show eplontersen slows disease progression in polyneuropathy patients

Positive topline results from a 35-week interim analysis of the Phase III NEURO-TTRansform study of Ionis Pharmaceutical and AstraZeneca’s eplontersen in patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), have been reported.

Eplontersen demonstrated a statistically significant and clinically meaningful change from baseline for the co-primary endpoints of percent change in serum transthyretin (TTR) concentration and the modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression, versus the historical placebo group.

The trial also met its key secondary endpoint of change from baseline in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), showing treatment with eplontersen significantly improved patient-reported quality of life versus the historical placebo group.

In the study, eplontersen demonstrated a favourable safety and tolerability profile with no specific concerns. The study data are consistent with the clinical profile seen across Ionis’ other LICA programmes, further validating advancements in the company’s LIgand-Conjugated Antisense technology, which could deliver potentially transformative treatments for a range of unmet medical needs. 

Based on these study results, the companies will seek regulatory approval for eplontersen for ATTRv-PN and plan to file a New Drug Application with the US Food and Drug Administration (FDA) this year.

“These encouraging data reinforce the safety profile of eplontersen and demonstrate clear evidence of its potential to provide much needed therapeutic benefit to patients living with hereditary transthyretin-mediated amyloid polyneuropathy,” commented Dr Teresa Coelho, a neurologist and neurophysiologist at Hospital Santo António, Centro Hospitalar Universitário do Porto, Portugal and an investigator for the NEURO-TTRansform study.

“We are pleased that the data in the NEURO-TTRansform study demonstrate eplontersen had a positive impact on disease progression, including improvement in neuropathy impairment and quality of life in a substantial number of patients. These highly statistically significant and clinically meaningful results put us on the cusp of providing a new therapeutic option for polyneuropathy patients living with this debilitating and fatal disease,” stated Dr Eugene Schneider, Ionis’ executive vice president and chief clinical development officer.

“We are grateful to the patients, families and clinicians who are participating in NEURO-TTRansform. Without their commitment the eplontersen programme would not have progressed as successfully as it has.”

The data from the 35-week interim analysis will be presented at an upcoming medical meeting later this year.