Roche’s recent investment of $310 million into metabolic therapy is yielding positive results, as its collaboration with Alnylam in the development of a hypertension medication, zilebesiran, has demonstrated promising outcomes in a phase 2 clinical trial.
In this trial, the two higher doses of zilebesiran, 300 mg, and 600 mg, led to a remarkable reduction of over 15 mmHg in mean 24-hour systolic blood pressure (SBP) after three months, compared to a placebo. This achievement met the primary endpoint of the KARDIA-1 trial, which involved 394 adult participants.
Notably, the medication also met key secondary endpoints by consistently sustaining SBP reduction over six months. Roche highlights that this supports the potential for a dosing regimen that could be administered quarterly or even biannually. The trial additionally revealed that zilebesiran effectively reduced serum angiotensinogen levels through month six while maintaining a favorable safety and tolerability profile.
However, it’s worth noting that there was a reported death of a zilebesiran-treated patient in the trial, attributed to cardiopulmonary arrest and considered unrelated to the drug. Furthermore, 3.6% of patients in the zilebesiran groups reported a serious adverse event, none of which were deemed drug-related, compared to 6.7% in the placebo group.
These encouraging results mark a significant milestone for Roche, which made a high-profile entry into the metabolic therapy field in July by investing $310 million upfront to secure full ex-US rights and co-US rights to zilebesiran from Alnylam. Additionally, Alnylam stands to receive up to $2.8 billion in milestone payments if zilebesiran reaches the market. Roche also retains the option to lead the drug’s development for potential indications beyond hypertension.
“These early results indicate the potential for zilebesiran to achieve sustained blood pressure reduction with quarterly or biannual dosing. Also, these data underscore the potential of this investigational medicine to provide transformative impact for many people living with uncontrolled hypertension.’’
– Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development
Zilebesiran is an RNAi therapeutic administered subcutaneously, targeting liver-expressed angiotensinogen. Besides the KARDIA-1 trial, the drug is part of a larger phase 2 study as an add-on therapy to medications like Pfizer’s Norvasc, Daiichi Sankyo’s Benicar, and indapamide. Enrollment for this study was completed in June, with top-line results expected in early 2024.
The positive outcomes from this trial support the continued development of zilebesiran and will help determine the optimal dosage and regimen for future studies. Roche’s Chief Medical Officer, Dr. Levi Garraway, expressed optimism about the potential of zilebesiran to provide a transformative impact for individuals living with uncontrolled hypertension, underscoring the significance of these early results.
