Breakthrough Advances in Hypertension Drug Pipeline in 2025 Bring New Hope to Over 1 Billion Patients Worldwide

According to the "Global Report on Hypertension 2025" released by the World Health Organization (WHO) in September this year, as of 2024, there are approximately 1.4 billion people aged 30-79 worldwide with hypertension, but only about one-fifth of them have their condition effectively controlled.

Although there are currently various drugs available that can effectively lower blood pressure, existing treatment options still fail to meet all therapeutic needs. Among them,Poor medication adherence is one of the important reasons affecting the low control rate of hypertension.If blood pressure remains uncontrolled for a long time, it will significantly increase the risk of serious diseases such as myocardial infarction, stroke, chronic kidney disease, and dementia.Currently, the medical community urgently needs more effective and longer-lasting antihypertensive therapies to help patients better manage their blood pressure.

Public information shows that currently there are dozens of new drug pipelines globally conducting clinical research on hypertension, with molecular types mainly focusing on small molecules and nucleic acid drugs, including some others.Types such as antibodies, polypeptides, and DNA vaccinesSince 2025, there have been several new advancements in the R&D pipeline targeting hypertension, especially in targetedAngiotensinogen (AGT)Oligonucleotide drugs show potential advantages of "long-acting blood pressure reduction" in clinical research, drawing significant attention from the industry.

Oligonucleotide Therapy Shows Long-Lasting Potential in Treating Hypertension

AGT is the most upstream target in the renin-angiotensin-aldosterone system (RAAS). This cascade reaction has been proven to play a role in blood pressure regulation, and its inhibition has a well-established antihypertensive effect.Oligonucleotide drugs, represented by siRNA and antisense oligonucleotides (ASO), directly reduce the expression of AGT at the source. They usually have a long duration of action and more persistent effects, which are expected to improve the current poor medication adherence among hypertensive patients.

Since the beginning of this year,Multiple new drugs have shown the potential to achieve "single-dose administration, long-lasting blood pressure reduction" in clinical research results.。

In November, Innovent Bio and SANEGENEBIO jointly developedsiRNA Drug Targeting AGTThe main results of the first-in-human Phase 1 clinical trial of IBI3016 have been announced.The study focused on healthy subjects and patients with mild hypertension.The data shows that after a single dose of the drug,The level of AGT in patients' serum was significantly and persistently reduced, with a maximum reduction of over 95%, which remained stable for 6 months.A decrease in blood pressure was observed in all dose groups at 3 months post-dosing, with good safety and tolerability demonstrated throughout the 6-month study period.

In September, Xianyan Biologics announced itsNovel small nucleic acid drugs developed based on RNA interference (RNAi) technologyLDR2402 Injection Completes First Patient Dosing in Phase 2 Clinical Trial. The product significantly reduced AGT levels in preclinical studies.The effect can last for more than 6 months after a single injection.As of now, the Phase 1 clinical trial of this product has completed the enrollment and dosing of all subjects. The data from the post-single-dose stage indicates excellent safety performance and has demonstrated the potential for long-acting blood pressure reduction with an injection every six months.

In August, Roche and Alnylam announced the launch of a Phase 3 clinical trial to evaluate whether their AGT-targeting siRNA therapy, zilebesiran, can reduce the risk of major cardiovascular adverse events in patients with uncontrolled hypertension. In a previous clinical study, KARDIA-3, a single dose of zilebesiran (300 mg subcutaneous injection every six months) was administered.A clinically meaningful reduction in office systolic blood pressure was achieved in all subjects. The antihypertensive effect reached statistical significance by the third month (a 5.0 mmHg reduction compared to placebo-adjusted), and the efficacy persisted until the sixth month.

In July, Yooking Pharmaceutical announcedInvestigational siRNA Innovative Drug YKYY029 InjectionThe first patient has been enrolled. This product focuses on the treatment of hypertension, and its mechanism of action is to inhibit the expression of AGT protein at the source.

In June, Bowang Pharmaceutical announced that BW-00163, a novel siRNA drug for hypertension targeting AGT, has entered Phase 2 clinical trials. This drug is a key component of the company's exclusive licensing agreement with Novartis.

In May, Syncon Biotech announced that SNK-2726, an siRNA drug targeting AGT, has been approved for clinical trials in China and the United States, and the first subject has been enrolled and dosed in a Phase 1 clinical trial in China. Huadong Medicine has reached a strategic cooperation with Syncon Biotech to jointly advance the development of SNK-2726 to a certain stage.

In March, Kardigan announced the initiation of a Phase 2 clinical trial to evaluateMonthly Subcutaneous Injection ASO TherapyTonlamarsen, Efficacy and Safety in Patients with Uncontrolled Hypertension. The drug is a GalNAc-modified ASO therapy targeting mRNA encoding AGT, lowering blood pressure by reducing liver production of AGT.

In addition to the above pipeline progress, there are currently several other oligonucleotide new drug pipelines for hypertension under research, which will not be listed here one by one.

Integrated CRDMO Platform Facilitates the Development of Hypertension Oligonucleotide Therapies

Through public channel research, there are more than ten oligonucleotide therapies targeting hypertension undergoing clinical studies globally, including siRNA and ASO therapies, with their targets mainly focused on AGT.

The rapid development of oligonucleotide drugs targeting AGT, coupled with GalNAc (N-acetylgalactosamine) conjugation technology—thisLiver-targeted delivery systemis inseparable from the successful development.GalNAc conjugation technology is becoming the main strategy for the delivery of oligonucleotide therapies to hepatocytes.Due toThe main synthesis site of AGT, an important target for hypertension treatment, is the liver.The advantages of GalNAc conjugation technology are particularly prominent in the field of hypertension oligonucleotide therapy development.

Jointly Promoting the Innovation and R&D of Oligonucleotide Drugs, Contract Research and Manufacturing Organizations Play an Important Role.For a long time, WuXi AppTec has supported global partners in meeting their needs at every stage from drug research (R), development (D) to commercial production (M). Through its unique integrated end-to-end CRDMO model, it accelerates the development of breakthrough therapies, benefiting patients sooner.WuXi AppTec GroupFocus on the integration of oligonucleotide and peptide research and development, as well as related chemical conjugate drugs.The CRDMO platform WuXi TIDES has established an integrated service platform around oligonucleotide drugs, covering the entire lifecycle from drug discovery, CMC development, to commercial production, accelerating the transformation of partners' innovative ideas into reality for the benefit of patients worldwide.

Taking GalNAc conjugation technology as an example, since its inception, GalNAc conjugation technology has been continuously iterated and upgraded, achieving significant progress in both chemical modification methods and the design and synthesis of multivalent molecules. Due to the affinity of the asialoglycoprotein receptor (ASGPR) for GalNAc being closely related to the number of its ligands, researchers have extensively explored and developed various trivalent and tetravalent GalNAc clusters and their conjugation strategies on oligonucleotides to improve delivery efficiency.

As the technology continues to mature, the synthesis and process development of GalNAc-conjugated drugs are becoming increasingly complex.The WuXi TIDES team has extensive experience in synthesizing GalNAc molecules, having synthesized more than 100 types of GalNAc molecules and their derivatives, including mono-GalNAc, tri-GalNAc, tetra-GalNAc, GalNAc amide, GalNAc PFP ester, GalNAc N3, and GalNAc-PEG conjugates. With comprehensive platform capabilities, WuXi TIDES can provide integrated services for GalNAc custom synthesis, process development, and production, supporting from drug discovery to clinical development and then to commercial production.

Small Molecule Drugs for Hypertension Treatment Achieve Multiple Breakthroughs

In addition to oligonucleotide drugs, 2025 also saw significant new progress in the small-molecule pipeline for hypertension, offering patients new potential treatment options.

In December, AstraZeneca announced that the New Drug Application (NDA) for its investigational therapy baxdrostat has been accepted by the U.S. FDA and granted Priority Review designation as an add-on combination therapy to other antihypertensive drugs for the treatment of adult patients with uncontrolled or treatment-resistant hypertension. The submission of this NDA is primarily based on data from the Phase 3 BaxHTN clinical trial: the addition of baxdrostat to standard therapy achieved both the primary endpoint and all secondary endpoints. At week 12, the mean change in seated systolic blood pressure (SBP) from baseline was a reduction of 15.7 mmHg in the 2 mg dose group, and a placebo-adjusted reduction of 9.8 mmHg from baseline, indicating that baxdrostat demonstrates significant and statistically meaningful blood pressure-lowering effects in patients with resistant hypertension.Baxdrostat is an investigational, once-daily, highly selective aldosterone synthase inhibitor (ASI) that controls blood pressure levels by targeting aldosterone, the hormone driving hypertension and its associated cardio-renal risks.

In May, Salubris' Sacubitril Alisartan Calcium Tablets (S086) were approved for marketing by China's NMPA for the treatment of mild to moderate essential hypertension. The drug is aAngiotensin II Receptor-Enkephalinase Dual Inhibitor, The mechanism of action is to achieve deeper blood pressure control by inhibiting enkephalinase while blocking the angiotensin II type 1 receptor (AT1). In June, another drug of Salubris, Alisartan Indapamide Sustained-Release Tablets, was also approved by China's NMPA for the treatment of essential hypertension. This drug is aAngiotensin II Receptor Blocker (ARB)/Diuretic Compound Sustained-Release Formulation, with Both Diuretic and Calcium Channel Blocking Effects.Not only that, the combination of Alisartan and Indapamide can reduce the adverse reactions of diuretics such as hypokalemia and increased uric acid, playing a role in enhancing efficacy and reducing toxicity.

In March, Mineralys Therapeutics announced positive results from two pivotal clinical trials of its investigational aldosterone synthase inhibitor (ASI), lorundrostat, in patients with uncontrolled hypertension and resistant hypertension. The company subsequently published the findings in The New England Journal of Medicine (NEJM): Updated results published: At week 12 of treatment, lorundrostat reduced the average 24-hour ambulatory systolic blood pressure by 13.9–15.4 mmHg, significantly outperforming the placebo group (7.4 mmHg).

Many other new drug pipelines for hypertension have made progress this year, and will not be listed one by one here.

In the field of hypertension treatment, scientific innovation has never stopped in response to unmet clinical needs. We look forward to witnessing more precise and long-acting therapies successfully emerge in the near future. In this process, WuXi AppTec will continue to accelerate bringing more breakthrough treatments to patients worldwide through its integrated, end-to-end CRDMO platform, supporting global partners.

References:

[1] Global report on hypertension 2025: high stakes: turning evidence into action. Retrieved Sep 23, 2025, from https://www.who.int/publications/i/item/9789240115569

[2] Hypertension. Retrieved April 22, 2025, from https://www.who.int/en/news-room/fact-sheets/detail/hypertension

[3] Official Websites of Various Companies

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