HELIOS-A Phase III study of ALN TTRsc02 meets all secondary endpoints in hATTR amyloidosis with polyneuropathy.- Alnylam Pharma

In HELIOS-A, patients treated with vutrisiran also showed improvement in exploratory cardiac endpoints including NT-proBNP and echocardiographic parameters relative to placebo, as well as technetium uptake, relative to baseline, in a planned cohort of patients. Vutrisiran also continued to demonstrate an encouraging safety and tolerability profile consistent with the previously reported Month 9 results. Alnylam previously announced that HELIOS-A met its primary and secondary endpoints at 9 months.

At 18 months, vutrisiran met all secondary endpoints in HELIOS-A, demonstrating statistically significant improvement in clinical endpoints compared to placebo and non-inferiority in serum TTR reduction compared to the within-study patisiran arm, specifically: Vutrisiran treatment (N=122) resulted in a 0.46 point mean decrease (improvement) in the modified Neuropathy Impairment Score (mNIS+7) from baseline at 18 months as compared to a 28.09 point mean increase (worsening) reported for the external placebo group (N=77), resulting in a 28.55 point mean difference relative to placebo (p equal to 6.5x10-20). Vutrisiran treatment also resulted in an mNIS+7 improvement relative to baseline at 18 months in 48 percent of patients, compared with 4 percent of patients who received placebo. Vutrisiran treatment resulted in a 1.2 point mean decrease (improvement) in Norfolk QoL-DN score from baseline at 18 months as compared to a 19.8 point mean increase (worsening) reported for the external placebo group, resulting in a mean 21.0 point difference relative to placebo (p equal to 1.8x10-10). Fifty-seven percent of patients treated with vutrisiran experienced improvement in quality of life relative to baseline at 18 months, compared with 10 percent of patients who received placebo.

In addition, Vutrisiran achieved statistically significant improvement in gait speed (10-MWT), nutritional status (mBMI), and disability (R-ODS) at 18 months, compared with the external placebo group. Vutrisiran treatment resulted in a 0.024 meters/second mean decrease in 10-MWT from baseline at 18 months as compared to a 0.264 meters/second mean decrease in the external placebo group, resulting in a mean 0.239 meters/second increase relative to placebo (p equal to 1.2x10-7). Vutrisiran treatment resulted in a 25.0 point mean increase (improvement) in mBMI from baseline at 18 months as compared to a 115.7 point mean decrease in the external placebo group, resulting in a 140.7 point mean increase relative to placebo (p equal to 4.2x10-15). The results were presented in an oral session at the Société Francophone du Nerf Périphérique (SFNP) Annual Meeting.