Hypertension Impacts 1.2B People - Alnylam's Gene Silencing Drug Candidate Hits the Mark in Phase 2 Study, Offering Hope

Alnylam Pharmaceuticals Inc's ALNY KARDIA-1 Phase 2 study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) for hypertension, met the primary endpoint.

Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche Holdings AG RHHBY.

The study demonstrated a dose-dependent, clinically significant reduction in 24-hour mean systolic blood pressure (SBP) measured by ambulatory blood pressure monitoring (ABPM) at Month 3, achieving a placebo-subtracted reduction greater than 15 mmHg (p less than 0.0001) with both 300 mg and 600 mg doses. 

The study also met key secondary endpoints, including a significant change in 24-hour mean SBP at Month 6 and a significant change in office SBP at Month 3 and 6 for all zilebesiran arms, compared to placebo. 

The study results indicate zilebesiran was associated with dose-dependent, potent, and durable knockdown of serum AGT levels through Month 6. 

Zilebesiran also demonstrated an encouraging safety and tolerability profile.

There was one death due to cardiopulmonary arrest in a zilebesiran-treated patient that was considered unrelated to the study drug. 

The KARDIA-2 Phase 2 study of zilebesiran combined with one of three standard classes of anti-hypertensive medications completed enrollment in June 2023. Topline results are expected in early 2024.

William Blair writes that it reaffirms the program's potential and underscores Alnylam's broader siRNA approach, and the analyst anticipates that the data presented will set a significant benchmark for efficacy in the field, particularly impacting Ionis Pharmaceuticals Inc IONS, which is actively developing its anti-sense oligonucleotide therapeutic.

Price Action: ALNY shares are up 0.92% at $203.31 on the last check Thursday.