Roche’s $310 million splash into the metabolic therapy pool two months ago already appears to be paying off, with its Alnylam-partnered hypertension med reducing blood pressure in a phase 2 trial.
The two higher doses of zilebesiran being trialed, 300 mg and 600 mg, both produced a more than 15-mmHg mean reduction in 24-hour systolic blood pressure (SBP) after three months compared to placebo, hitting the primary endpoint of the 394-adult KARDIA-1 trial.
In addition, the drug hit the key secondary endpoints of consistent and sustained reductions of SBP at six months, which Roche said supported a quarterly or even biannual dosing regimen. “In addition, the study showed that zilebesiran was associated with a potent and durable reduction of serum [angiotensinogen] levels through month six while demonstrating an encouraging safety and tolerability profile,” the Big Pharma added in the Sept. 7 release.
According to Alnylam, there was a death of a zilebesiran-treated patient in the trial, which was due to cardiopulmonary arrest and considered unrelated to the drug. A total of 3.6% of patients in the zilebesiran cohorts reported a serious adverse event—none of which were considered related to the drug—compared to 6.7% who received placebo.
The readout will be welcome news at Roche. The company made arguably its most high-profile entry into the metabolic space in July when it paid Alnylam $310 million upfront for the full ex-U.S. rights and co-U.S. rights to the therapy. Should zilebesiran reach the market, Alnylam will also be in line for up to $2.8 billion in milestone payments. Roche still has the option to spearhead the development of the drug for any future indications beyond hypertension.
“These early results indicate the potential for zilebesiran to achieve sustained blood pressure reduction with quarterly or biannual dosing,” said Roche’s chief medical officer Levi Garraway, M.D., Ph.D., in this morning’s release. “Also, these data underscore the potential of this investigational medicine to provide transformative impact for many people living with uncontrolled hypertension.’’
Zilebesiran is a subcutaneously administered RNAi therapeutic that targets liver-expressed angiotensinogen. Alongside KARDIA-1, the drug remains in another, larger phase 2 study as an add-on therapy to Pfizer’s Norvasc, Daiichi Sankyo’s Benicar and indapamide. Enrollment completed in June with a top-line readout expected in early 2024.
Alnylam said today’s results support continued development of zilebesiran, and the data will be used to help determine the optimal dose and regimen for future studies.