June 16, 2024

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Over $3 billion: Roche invests Alnylan Zilebesiran RNAi Therapy for Hypertension

Over $3 billion: Roche invests Alnylan Zilebesiran RNAi Therapy for Hypertension


Over $3 billion: Roche invests Alnylan Zilebesiran RNAi Therapy for Hypertension.

On July 24, 2023, Roche announced a new partnership with Alnylam to jointly develop and commercialize zilebesiran, an RNAi therapy for hypertension, which is currently in phase 2 development .

Under the terms of the agreement, Alnylam will receive an upfront payment of $310 million and is eligible to receive additional payments, including development milestones over the next few years, as well as regulatory and sales milestones, for a potential transaction value of up to $2.8 billion .


Over $3 billion: Roche invests Alnylan Zilebesiran RNAi Therapy for Hypertension




About Hypertension Treatment


Currently, more than 1 billion people worldwide suffer from high blood pressure . Hypertension is a leading cause of premature death, cardiovascular disease, and chronic kidney disease worldwide, and its prevalence is steadily increasing globally with an aging population and the prevalence of risk factors such as obesity, physical inactivity, and unhealthy diet.


Despite effective antihypertensive treatments, nearly half of hypertensive patients fail to achieve guideline-recommended blood pressure goals , leaving this population at residual risk for myocardial infarction, stroke, renal disease progression, and death. Poor adherence (daily oral intake) is one of the current challenges in optimizing hypertension treatment .


For the treatment bottleneck of hypertension, the main advantages of siRNA therapy include:



Alnylam has been deeply involved in RNA technology for many years. The current long-acting technology can support up to one injection per year, and the injection frequency of Zilebesiran is twice a year. From the perspective of compliance, it is significantly better than most current oral drugs. It is expected to solve the problem of false drug resistance by improving compliance.


Bypassing the drug resistance mechanism:

At present, the scientific community has proposed that one of the mechanisms of hypertension drug resistance is RAAS-escape, that is, inhibiting AT1R may increase the expression of AGT; Zilebesiran directly acts on reducing the expression of AGT, which can theoretically bypass this drug resistance mechanism.


Some domestic companies have also carried out research and development of small nucleic acid drugs for high blood pressure. Among them, the antihypertensive small nucleic acid drugs of Bowang Pharmaceutical have entered the first phase of clinical trials. In addition antihypertensive small nucleic acid drugs cooperated by Gambly, Xinlitai and Anlong Biotech are still in the preclinical stage.



About RNAi

RNAi (RNA interference), a natural cellular process of gene silencing, is one of the most promising and fastest-growing frontiers in biology and drug development today.

Its discovery was hailed as “a major scientific breakthrough that happens every decade or so” and won the 2006 Nobel Prize in Physiology or Medicine.

By harnessing the natural RNAi biological process that occurs in cells, a new class of drugs known as RNAi therapeutics is now a reality.

Small interfering RNA (siRNA) is the molecule that mediates RNAi and constitutes Alnylam’s RNAi therapeutics platform, which works upstream of today’s drugs by effectively inhibiting the production of gene precursor messenger RNA (mRNA) encoding disease-causing proteins or disease pathway proteins, thereby preventing them.

It’s a revolutionary approach that has the potential to transform the treatment of patients with genetic and other disorders.




About Zilebesiran

Zilebesiran is a subcutaneously administered RNAi therapy targeting angiotensinogen (AGT) currently in Phase 2 clinical development for the treatment of hypertension in high-need populations.

AGT is the most upstream precursor of the renin-angiotensin-aldosterone system (RAAS), a cascade whose role in blood pressure (BP) regulation has been demonstrated, and inhibition of AGT has well-established antihypertensive effects.

Zilebesiran inhibits the synthesis of AGT in the liver, which may result in a persistent reduction of AGT protein and ultimately a decrease in angiotensin (Ang) II.

Zilebesiran uses Alnylam’s Enhanced Stable Chemical Enhancement (ESC+) GalNAc-conjugate technology, which can be injected subcutaneously with higher selectivity and a broader therapeutic index.

The safety and effectiveness of Zilebesiran have not been confirmed or evaluated by the FDA, EMA, or any other health agency.


Over $3 billion: Roche invests Alnylan Zilebesiran RNAi Therapy for Hypertension





Over $3 billion: Roche invests Alnylan Zilebesiran RNAi Therapy for Hypertension

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