Analysts Express Confidence in Alnylam's Hypertension Drug Despite Mixed Trial Data

On Sunday, Alnylam Pharmaceuticals Inc. ALNY presented results from the KARDIA-2 Phase 2 study, which evaluated the efficacy and safety of a single subcutaneous dose of zilebesiran when added to one of three standard-of-care antihypertensives. 

The company announced the topline results from the KARDIA-2 study in March 2024.

When added to the standard of care, indapamide and, amlodipine, zilebesiran respectively achieved reductions of 12.1 mmHg (p<0.001) and 9.7 mmHg (p<0.001) in the primary endpoint of change from baseline in 24-hour mean systolic blood pressure at three months.

However, when added to olmesartan, the experimental drug delivered a 4 mmHg reduction, missing statistical significance (p=0.036). 

Similarly, when added to the standard of care, indapamide and, amlodipine, zilebesiran, respectively, achieved reductions of 11.0 mmHg (p<0.001) and 7.9 mmHg (p<0.001) in the change from baseline in 24-hour mean systolic blood pressure at six months.

However, statistical significance was missed in the olmesartan arm, with a reduction of 1.6 mmHg (p=0.26).

Alnylam Pharmaceuticals and its partner Roche Holdings AG RHHBY have initiated a Phase 2 KARDIA-3 study of zilebesiran on top of 2-4 anti-hypertensive medicines and are planning a Phase 3 CVOT, JMP Securities writes. 

The analyst recommends owning Alnylam shares ahead of HELIOS-B data on AMVUTTRA in ATTR-CM in late June or early July. If positive, Alnylam will file the FDA marketing application by the end of 2024 and use a priority review voucher for approval in 2H 2025. 

JMP reiterates the Overweight rating, with a price target of $217.

William Blair writes that although there could be noise in interpreting the Olmesartan cohort of KARDIA-2, the zilebesiran data is strong here and has invoked genuine interest.

With approximately 219 million patients in seven key markets, the primary hypertension market is substantial, making the zilebesiran market significant for Alnylam financially. 

While investor attention is on the HELIOS-B cardiovascular outcomes trial for vutrisiran in TTR-cardiomyopathy, expected in June or early July, 

Alnylam is actively progressing its RNA-targeted therapeutics pipeline. Therefore, William Blair maintains the Outperform rating on Alnylam.

Price Action: ALNY shares are up 2.46% at $157.34 on the last check Monday.