Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic that targets angiotensinogen (AGT), which regulates blood pressure and fluid balance, currently in Phase 2 development for the treatment of hypertension
Roche partners with US-based Alnylam Pharmaceuticals. (Credit: F. Hoffmann-La Roche Ltd)
Swiss drugmaker Roche has partnered with US-based biopharmaceutical company Alnylam Pharmaceuticals to develop and market the latter’s investigational drug zilebesiran.
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic that targets angiotensinogen (AGT), which regulates blood pressure and fluid balance.
The drug is currently being developed in the Phase 2 programme for the treatment of hypertension in patients with high cardiovascular risk.
Under the terms of the partnership agreement, Alnylam and Roche will jointly develop and commercialise zilebesiran in the US, by equally sharing the associated costs and profits.
Alnylam will lead a joint clinical development plan for the first indication, which includes a cardiovascular outcomes trial before the submission of zilebesiran for regulatory approval.
Roche will obtain exclusive rights to commercialise the drug outside the US, and Roche may lead development for additional indications in the future.
Alnylam will receive an upfront payment of $310m and is eligible to receive up to $2.8bn in development, regulatory and commercial milestone payments, and royalties on sales.
Roche Pharma CEO Teresa Graham said: “We are excited to work together with Alnylam and leverage our strong R&D capabilities, our leadership in cardiovascular diagnostics and our global commercial footprint to further develop and provide this promising therapy with best-in-disease potential to patients.
“Throughout our history, we have redefined the standard of care across various disease areas. Together with a strong partner like Alnylam, we are looking forward to making a significant impact for patients living with hypertension at high cardiovascular risk and potentially other cardiovascular indications.”
In the Phase 1 study, zilebesiran resulted in dose-dependent reductions in serum AGT, and tonic blood pressure control throughout 24 hours, compared to placebo.
The drug achieved a consistent and durable blood pressure reduction, which was sustained up to six months after single doses of ≥200mg.
Zilebesiran also showed an acceptable safety profile supporting continued clinical development.
Alnylam assessed the safety and efficacy of zilebesiran in the Phase 2 KARDIA programme, as a monotherapy and in combination with one of three standard antihypertensive medications.
The company leveraged its Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology for zilebesiran, which enables subcutaneous dosing with increased selectivity.
Alnylam CEO Yvonne Greenstreet said: “We are thrilled to announce this collaboration, as it combines Alnylam’s proven track record in RNAi therapeutics with Roche’s global commercial reach, commitment to innovation and desire to transform the landscape for patients with severe cardiovascular diseases.
“With this collaboration, we now can develop zilebesiran in a more robust way, allowing us to have cardiovascular outcomes data in hand at launch to ensure results relevant not only for health authorities but also for access and clinical practice in order to ultimately reach as many patients as possible.”