Pharma Focus Europe

Ionis announces FDA acceptance of New Drug Application for eplontersen for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN)

Wednesday, March 08, 2023

Ionis Pharmaceuticals (Nasdaq: IONS) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) for eplontersen, an investigational antisense medicine for the treatment of people 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.

In its acceptance letter, the FDA stated that it has not identified any review issues and did not make any additional data requests. The FDA also noted that it is not planning to hold an advisory committee meeting to discuss the application.

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 fifteen years of disease onset.

"We are excited by today's FDA acceptance of our NDA filing as it brings Ionis and our partner, AstraZeneca, one step closer to making eplontersen available to patients with ATTR polyneuropathy," said Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis. "Significant reductions in TTR protein levels were observed during the NEURO-TTRansform 35-week interim analysis. 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). 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 (p<0.0001) in the co-primary endpoint of serum transthyretin (TTR) concentration compared to baseline. Eplontersen also demonstrated a significant treatment effect on the co-primary endpoint of modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression, with a statistically significant difference in mean change from baseline versus the external placebo group (p<0.0001). The study met its key secondary endpoint of change from baseline in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), showing that treatment with eplontersen significantly improved patient-reported quality of life compared to the external placebo group (p<0.0001). Eplontersen also demonstrated a favorable safety and tolerability profile.

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). In December 2021, Ionis and AstraZeneca entered into a strategic collaboration to develop and commercialize eplontersen. Eplontersen is being jointly developed and commercialized by both companies in the U.S. and will be developed and commercialized in the rest of the world by AstraZeneca, with the exception of Latin America. In January 2022, eplontersen was granted Orphan Drug Designation in the U.S. by the FDA.

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



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