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Ionis Pharma completes enrollment in phase 3 CARDIO-TTRansform study of eplontersen in patients with TTR-mediated amyloid cardiomyopathy

Ionis Pharmaceuticals, Inc. announced the completion of enrollment in the phase 3 CARDIO-TTRansform cardiovascular outcomes study of eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a large and growing patient population at risk of life-threatening cardiovascular (CV) events. The study enrolled more than 1,400 patients.

Eplontersen is an investigational antisense medicine designed to inhibit the production of transthyretin and slow the progression of cardiomyopathy for people living with hereditary or wild-type ATTR-CM.

"CARDIO-TTRansform is the largest and most comprehensive ATTR-CM study ever conducted. The evaluation of eplontersen in this broad, diverse patient population will enable robust and clinically meaningful analysis of the composite endpoint of CV mortality and recurrent CV events," said Eugene Schneider, M.D., executive vice president and chief clinical development officer for Ionis. "It will also allow us to gather data from important patient subsets, including patients with or without stabilizer therapy and those with or without hereditary disease within the evolving ATTR-CM landscape. We look forward to reporting results as early as the first half of 2025."

As part of a global development and commercialization agreement, Ionis and AstraZeneca are seeking regulatory approval for eplontersen for the treatment of transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) in the US and plan to seek regulatory approval in Europe and other parts of the world. The US Food and Drug Administration accepted the New Drug Application for eplontersen for the treatment of ATTRv-PN with a PDUFA action date of December 22, 2023. Eplontersen was granted Orphan Drug Designation in the US.

CARDIO-TTRansform is a global, double-blind, randomized, placebo-controlled phase 3 cardiovascular outcome study in more than 1,400 patients with ATTR cardiomyopathy (ATTR-CM). It is designed to compare eplontersen to placebo in patients with both wild-type ATTRwt-CM and hereditary ATTRv-CM who are either naïve to treatment or on a currently available standard of care. The primary composite endpoint is cardiovascular (CV) mortality and recurrent CV clinical events comparing the two study arms up to week 140. Secondary endpoints include the change from baseline in the 6-minute walk test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at week 121, as well as the rates of CV mortality, CV clinical events and all-cause mortality at week 140.

Eplontersen is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of TTR protein. Eplontersen is being developed as a monthly self-administered subcutaneous injection to treat all types of ATTR. ATTR amyloidosis is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to organ failure and eventually death.

Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed and potentially fatal disease. It is caused by the accumulation of misfolded TTR protein in the cardiac muscle. Patients experience ongoing debilitating heart damage resulting in progressive heart failure, which results in death within three to five years from disease onset. ATTR-CM includes both the genetic and wild-type form of the disease. Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM.

For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care. Ionis currently has four marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises.