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Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. This review highlights ten promising antihypertensive drug candidates with the potential to address pulmonary arterial hypertension (PAH), resistant hypertension and uncontrolled hypertension.
Aprocitentan, developed by Janssen NYSE:JNJ) and Idorsia (SIX:IDIA), is an experimental oral drug designed to treat resistant hypertension. As a dual endothelin receptor antagonist (ERA), it effectively blocks the binding of ET-1 to both ET A and ET B receptors. The drug has a low likelihood of interacting with other medications and its mechanism of action is well-suited for treating resistant hypertension. In clinical trials, aprocitentan demonstrated better blood pressure reduction than placebo, with the effects lasting up to week 40, and was generally well-tolerated by patients. (Text continues beneath the following table:)
| Drug Name | Phase of Development | Company | Target Indication | Notes |
|---|---|---|---|---|
| Aprocitentan | Phase 3 | Janssen/Idorsia | Resistant hypertension | Idorsia filed an NDA with the FDA for difficult-to-control hypertension in December 2022 |
| Sotatercept | Phase 3 | Merck | Pulmonary arterial hypertension (PAH) | Advanced to Phase 3 with positive results |
| Ralinepag | Phase 3 | United Therapeutics | Pulmonary arterial hypertension (PAH) | Encouraging Phase 2 results; currently in Phase 3 |
| XXB750 | Phase 2 | Novartis | Resistant hypertension and heart failure with preserved ejection fraction | Pursuing indications for Resistant Hypertension and Heart Failure with Preserved Ejection Fraction |
| Zilebesiran | Phase 2 | Alnylam | Uncontrolled hypertension | Novel mechanism of action |
| IONIS-AGT-LRx | Phase 2 | Ionis Pharmaceuticals | Uncontrolled hypertension | Novel antisense oligonucleotide inhibitor |
| Baxdrostat | Phase 2 | AstraZeneca/CinCor | Resistant hypertension | Potentially addresses a challenging form of hypertension with limited treatment options, but underwhelming performance in phase 2 HALO trial |
| L606 | Phase 3 | Pharmosa Biopharm Inc. | Pulmonary arterial hypertension (PAH) | Positive results from phase 2 |
| LTP001 | Phase 2 | Novartis | Pulmonary arterial hypertension (PAH) | Phase 2 study currently recruiting |
Merck & Co.’s (NYSE: MRK) sotatercept has received breakthrough therapy status from FDA and reported positive Phase 3 results for PAH pulmonary arterial hypertension (PAH), a life-threatening condition involving high blood pressure in the arteries of the lungs. Additionally, Arena Pharmaceuticals, recently acquired by Pfizer (NYSE:PFE), has demonstrated encouraging Phase 2 results for the antihypertensive ralinepag, which is now in Phase 3 for PAH. This drug candidate could potentially offer a new therapeutic strategy for PAH patients who do not respond well to existing treatments.
Drugs in Phase 2 trials include XXB750 from Novartis (NYSE:NVS), which holds potential for resistant hypertension, a condition that often requires complex and aggressive treatment strategies. This antihypertensive compound may offer a new treatment option for patients who fail to achieve blood pressure control with standard therapies. Also in Phase 2 is Alnylam’s (Nasdaq:ALNY) zilebesiran, which has a novel mechanism of action for hypertension, potentially leading to more effective and personalized treatment options.
In the same category is IONIS-AGT-LRx from Ionis (Nasdaq:IONS), which targets uncontrolled hypertension, a condition where blood pressure remains high despite treatment with medications. This investigational drug aims to improve blood pressure control for patients who have difficulty managing their hypertension. Baxdrostat, CinCor‘s lead asset, is also in Phase 2 for resistant hypertension. AstraZeneca (LON:AZN) acquired the company in February, further bolstering the drug’s prospects for successful development.
The following table is based on factors such as clinical trial phases, obtained results, and potential impact on patient populations. We selected the following investigational drugs based on their potential impact in hypertension and PAH management from recent clinical studies. Criteria include the stage of development, target indications, which included PAH and uncontrolled and resistant hypertension. We also considered the novelty of the drug candidates’ mechanism of action as well as company reputation and experience.