Roche announced on 24-July-2023, a fresh collaboration with Alnylam Pharmaceuticals to develop and market zilebesiran, a RNAi therapy now in Phase II for the management of hypertension. Over 1.2 billion individuals worldwide suffer from hypertension, which is the primary independent avoidable risk factor for mortality and disability. Approximately 80% of these adults are unable to successfully manage their blood pressure.
Based on the promising Phase I data, zilebesiran may be the best-in-disease treatment for the condition and have a game-changing effect, particularly for individuals with hypertension who are at high cardiovascular risk. Due to the prospective biennial subcutaneous dosing schedule, it also has the potential to improve adherence and compliance to therapy. Additionally, zilebesiran may assist patients in other cardiovascular diseases with significant unmet medical needs.
Terms of the agreement between Alnylam Pharmaceuticals and Roche
Under the terms of the agreement, Alnylam will receive an upfront payment of $310m and is eligible to receive development, regulatory and commercial milestones including substantial near-term milestones, together with equal profit and loss share in the US and royalties ex-US.
This partnership will allow both partners to pursue a joint development plan and commercialization approach to unlock the full value of zilebesiran. As a part of this agreement, Alnylam and Roche will co-commercialize zilebesiran in the U.S. and share cost and profits equally. Outside the U.S. Roche obtains exclusive commercialisation rights. Alnylam will lead a joint clinical development plan for the first indication with Roche’s participation, which includes a cardiovascular outcomes trial prior to submission of zilebesiran for regulatory approval, with all development costs shared by Alnylam and by Roche. Roche may lead development for additional indications in the future.
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,” said Teresa Graham, CEO Roche Pharma. “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.”
“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,” said Yvonne Greenstreet MBChB, Chief Executive Officer of Alnylam. “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.”
In a Phase I study, zilebesiran was associated with dose-dependent decreases in serum angiotensinogen (AGT) when compared to placebo, leading to tonic blood pressure control with consistent and long-lasting blood pressure reduction over the course of a 24-hour period, sustained for up to six months after single doses of 200 mg. Additionally, zilebesiran showed a respectable safety profile that supports continuing clinical development. In Alnylam’s KARDIA Phase II clinical programme, zilebesiran’s safety and effectiveness are being studied as a monotherapy (KARDIA-1) or in combination with one of three standard-of-care antihypertensive drugs (KARDIA-2).
About zilebesiran
Zilebesiran is a research-stage, subcutaneously given RNAi therapy that targets angiotensinogen (AGT) and is being developed for the treatment of hypertension in populations with a high unmet medical need. The Renin-Angiotensin-Aldosterone System (RAAS), a cascade that has been shown to regulate blood pressure (BP), has the Renin-Angiotensin-Aldosterone System (AGT) as its most upstream predecessor. Its suppression has been shown to have established anti-hypertensive effects. Zilebesiran prevents the liver from producing AGT, which may result in long-lasting decreases in AGT protein and subsequently in the vasoconstrictor angiotensin (Ang) II. Zilebesiran makes use of the ESC+ GalNAc-conjugate technology from Alnylam, which provides subcutaneous dosage with enhanced selectivity and a broad therapeutic index. The FDA, EMA, or any other health authority have not established or assessed zilebesiran’s safety or effectiveness.
About hypertension
High blood pressure, often known as hypertension, is a significant risk factor for premature death and the world’s most common cause of cardiovascular disease. Cognitive dysfunction and subtle target organ damage, such as left ventricular hypertrophy, might be early symptoms of hypertension. Chronic kidney disease and end-stage renal disease, dementia, and Alzheimer’s disease can all develop over time as a result of uncontrolled hypertension, as can ischemic and hemorrhagic stroke, coronary artery disease, heart failure, peripheral artery disease, chronic kidney disease, and end-stage renal disease.
Fewer than 20% of persons with hypertension are able to successfully control their blood pressure despite the availability of multiple classes of effective antihypertensive medications and well-established management techniques like lifestyle changes.
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.
Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.
