Roche, Alnylam ink potential $2.8B RNAi partnership for hypertension
Published: Jul 24, 2023
By Tristan Manalac
Roche has entered into a strategic development and commercialization agreement with Alnylam Pharmaceuticals to advance the latter’s investigational RNA interference therapeutic zilebesiran for hypertension, the companies announced Monday.
Under the deal, Roche will make an upfront payment of $310 million in cash. Alnylam is also entitled to development, regulatory and sales milestones, with a potential contract value of up to $2.8 billion. The Cambridge, Mass.-based, RNAi-focused biotech will also be eligible for an equal profit share in the U.S., where it will commercialize zilebesiran together with Roche.
In return, Roche will hold the exclusive right to commercialize zilebesiran outside the U.S., while Alnylam will receive up to low double-digit royalties on net overseas sales.
Alynlam will also take charge of zilebesiran’s clinical development for its first indication, hypertension, with Roche’s participation. Alnylam will shoulder 40% of the costs, while Roche will contribute 60%. Roche will take charge of the development for all additional indications in the future.
Monday’s agreement combines “Alnylam’s proven track record in RNAi therapeutics with Roche’s global commercial reach,” Alnylam CEO Yvonne Greenstreet said in a statement.
“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,” Greenstreet said.
Designed to be administered subcutaneously, zilebesiran is an investigational RNAi therapeutic that works by suppressing the production of the angiotensinogen peptide in the liver. Angiotensinogen is the most upstream precursor in the renin-angiotensin-aldosterone cascade, the inhibition of which has been shown to help regulate blood pressure and prevent hypertension.
A Phase I study confirmed that zilebesiran was significantly better than placebo at reducing antiogensinogen levels in a dose-dependent manner. At a dose level of at least 200 mg, zilebesiran treatment also led to durable blood pressure reduction over 24 hours, an effect that was durable for up to six months.
Based on this early-phase performance, Alnylam believes that zilebesiran could have best-in-disease treatment potential for hypertension patients deemed to be at high cardiovascular risk. Its administration schedule, which could potentially involve biannual injections, could also help improve treatment adherence among patients.
Alnylam is currently running the Phase II KARDIA program to evaluate the safety and efficacy of zilebesiran. With almost 400 patients enrolled, KARDIA-1 will assess zilebesiran as a monotherapy for mild-to-moderate hypertension, while KARDIA-2 will evaluate it in combination with one of three standard antihypertensive agents in 630 patients.