With a Prescription Drug User Fee Act action date of Dec. 22, 2023, eplontersen is an antisense medicine to treat patients living with hereditary transthyretin-mediated amyloid polyneuropathy, which results in nerve damage.
The FDA has accepted for review a new drug application (NDA) for eplontersen, an investigational antisense medicine to treat patients living with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). The application has been given a Prescription Drug User Fee Act (PDUFA) action date of Dec. 22, 2023.
Patients with ATTRv-PN experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor function. These patients accumulate TTR in other major organs, which progressively compromises their function and eventually leads to death within five to 15 years of disease onset.
Developed by Ionis Pharmaceuticals, eplontersen is an investigational medicine designed to reduce the production of transthyretin (TTR) protein to treat both hereditary and non-hereditary forms of ATTR amyloidosis (ATTR). The FDA has granted eplontersen orphan drug designation. In December 2021, Ionis and AstraZeneca entered into a strategic collaboration to develop and commercialize eplontersen.
“Significant reductions in TTR protein levels were observed during the NEURO-TTRansform 35-week interim analysis,” Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis, said in a press release. “Overall, the interim analysis demonstrated eplontersen has the potential to make a positive impact on disease progression and improve quality of life in a substantial number of patients."
The NDA is based on results from the global phase 3 NEURO-TTRansform study presented at the International Symposium on Amyloidosis (ISA). Eplontersen achieved an 81.2% reduction in the co-primary endpoint of serum transthyretin (TTR) concentration from baseline, demonstrating reduced TTR protein production. Eplontersen demonstrated a favorable safety and tolerability profile.
In the 35-week interim analysis, eplontersen demonstrated a statistically significant and clinically meaningful change from baseline for its co-primary and key secondary endpoints compared to the external placebo group. In the study, eplontersen achieved a significant mean reduction in the co-primary endpoint of serum transthyretin (TTR) concentration compared with baseline.
Eplontersen also demonstrated a significant treatment effect on the co-primary endpoint of modified Neuropathy Impairment Score +7, a measure of neuropathic disease progression, with a statistically significant difference in mean change from baseline versus the external placebo group. The study met its key secondary endpoint of change from baseline in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy, showing that treatment with eplontersen significantly improved patient-reported quality of life compared with the external placebo group.