On July 9, Ionis Pharmaceuticals fell 14.75% in pre-market trading, trading at $74.68/share, with turnover of $86,200. The sharp decline was triggered by the announcement that the Phase 3 Cardio-TTRansform trial for eplontersen in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) failed to meet its primary efficacy endpoint.

The trial, conducted in partnership with AstraZeneca, evaluated a composite outcome of cardiovascular mortality and recurrent cardiovascular clinical events up to week 140 compared with placebo. The companies stated that in the contemporary patient population treated with standard of care, including a majority on a stabilizer, adding eplontersen did not provide a statistically significant benefit. Ionis and AstraZeneca plan to continue analyzing the full data and share results at the European Society of Cardiology Congress in August.

ATTR-CM is a fatal disease predominantly affecting the heart. Eplontersen had been positioned as a key pipeline asset for Ionis targeting all types of ATTR, making this clinical setback a significant blow to the company's commercial outlook in cardiovascular rare disease.

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