Table 4.
New drugs in phase 2 and 3 clinical development
| Drug | Mechanism of action | Clinical trials (acronym, NCT Identifier Number) | |
|---|---|---|---|
| Antiarrhythmics | Etripamil, nasal spray | Short-acting L-type Ca2+ channel blocker | Paroxysmal supraventricular tachycardia: NCT04952610; NODE-202, NCT05763953; CT05410860 |
| CRD-4730 | CaMKII inhibitor | Catecholaminergic polymorphic ventricular tachycardia: NCT06658899, NCT06005428 | |
| Antiobesity drugs | Cagrisema | Semaglutide plus the long-acting amylin analogue cagrilintide | T2D ± obesity: NCT064037 NCT0617636561; NCT06221969; REIMAGINE 1, NCT06323174; REIMAGINE 2, NCT06065540; REIMAGINE 3, NCT06323161, REIMAGINE 5, NCT06534411; REDEFINE 2, NCT05394519. Overweight or obesity: NCT06388187; REDEFINE 1, NCT05567796; NCT05813925; NCT06207877; NCT06267092; REDEFINE 6, NCT05996848. CKD + T2D + overweight/obesity: NCT06131372 |
| Orforglipron (LY3502970) | GLP-1 receptor agonist | T2D: ACHIEVE-J, NCT06010004; ACHIEVE-2, NCT06192108; ACHIEVE-5, CT06109311. Obese/overweight: ATTAIN-1, NCT05869903; ATTAIN-MAINTAIN, NCT06584916. Obstructive sleep apnoea: ATTAIN-OSA, NCT06649045 | |
| Retatrutide (LY3437943) | Agonist of GIP, GLP-1, and glucagon receptors | Obesity: TRIUMPH-1, NCT05929066; TRIUMPH-5, NCT06662383. Overweight/obesity + T2D: TRIUMPH-2, NCT05929079. Overweight/obesity + knee osteoarthritis: TRIUMPH-4, CT05931367. Obesity + CVD: TRIUMPH-3, NCT05882045; TRIUMPH-OUTCOMES, NCT06383390. Overweight/obesity + CKD ± T2D: NCT05936151. T2D: TRANSCEND-T2D-1, 2, 3 (NCT06354660, NCT06260722, NCT06297603) | |
| Survodutide | GLP-1 and glucagon receptor agonist | Overweight/obesity: NCT06492135; SYNCHRONIZE™JP: NCT06176365; SYNCHRONIZE™—CVOT, NCT06077864 | |
| Anticoagulants | Abelacimab (MAA868) | mAb that binds to the catalytic domain of FXI and prevents its activation | AF vs. rivaroxaban: AZALEA-TIMI 71, NCT04755283. High-risk patients with AF unsuitable for OAC: LILAC-TIMI 76, NCT05712200. Treatment of cancer-associated VTE: ASTER, NCT05171049; MAGNOLIA, NCT05171075 |
| ML-2060 | mAb that binds and inhibits FXIa activation | ESKD on haemodialysis: NCT05027074 | |
| REGN9933 | mAb that binds and inhibits FXIa activation | Peripherally inserted central catheter: ROXI-CATH, NCT06299111 | |
| Asundexian | Small molecule that targets the active site of FXIa and blocks its activity | AF ineligible for OAC: OCEANIC-AFINA. Secondary stroke prevention: OCEANIC-STROKE, NCT05686070 | |
| Milvexian | Small molecule that to the active site of FXIa and blocks its activity | Post-MI: LIBREXIA-ACS, NCT05754957. Secondary stroke prevention: LIBREXIA-STROKE, NCT05702034. AF vs. apixaban: LIBREXIA-AF, NCT05757869 | |
| Antiplatelets | Glenzocimab | Humanized GPVI-specific Fab fragment 9O12 against the extracellular domains of GPVI | STEMI: LIBERATE, ISRCTN15443962 |
| Diabetic cardiomyopathy | AT-001 | Highly selective aldose reductase inhibitor | Diabetic cardiomyopathy: NCT04083339 |
| Dyslipidaemia | Enlicitide decanoate | Oral PCSK9 inhibitor | Hypercholesterolaemia: CORALreef Lipids, NCT05952856; CORAreef-extension, NCT06492291. Versus ezetimibe ± bempedoic acid: CORALreef AddOn, NCT06450366. HeFH: CORALreef HeFH, NCT05952869. MACE: CORALreef Outcomes, NCT06008756 |
| Lepodisiran | siRNA targeting Lp(a) | Elevated Lp(a): NCT05565742; ACCLAIM-Lp(a), NCT06292013 | |
| Lerodalcibep | Recombinant fusion protein of a PCSK9-binding domain (adnectin) and human serum albumin | Patients with CVD on statins: LIBerate-CVD, NCT04797247. CVD or at high-risk for CVD: LIBerate-HR, NCT04806893; LIBerate-VI, NCT05004675. HoFH, HeFH, and high-risk CVD patients: LIBerate-OLE, NCT04798430 | |
| Muvalaplin | Oral small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction | Elevated lipoprotein(a) at high risk for CV events: KRAKEN, NCT05563246 | |
| Obicetrapib | Highly selective cholesteryl ester transfer protein inhibitor | Elevated Lp(a) levels: VINCENT, NCT06496243. Plus statins: ROSE, NCT04753606. On top of lipid-modifying therapies: BROADWAY, NCT05142722. Plus ezetimibe: TANDEM, NCT06005597. HeFH: BROOKLYN. ASCVD: PREVAIL, NCT05202509 | |
| Olezarsen | Ligand conjugated ASO targeting apoC-III | HT: NCT05681351; CORE, NCT05079919; CORE2, NCT05552326). FCS: NCT05130450. FCS treated with volanesorsen: NCT05185843. HT and ASCVD, or severe HT: ESSSENCE, NCT05610280 | |
| Olpasiran | siRNA that prevents assembly of Lp(a) | ASCVD: OCEAN(a) DOSE, NCT05581303 | |
| Pelacarsen | ASO targeting the mRNA transcribed from the LPA gene | Elevated Lp(a) + ASCVD: Lp(a)HORIZON, NCT04023552; OLE, NCT05900141; NCT06267560; NCT05305664. Calcific aortic valve stenosis: NCT05646381 | |
| Plozasiran (ARO-APOC3) | siRNA targeting the hepatic production of apo C-III | Mixed dyslipidaemia: NCT05413135. Severe HT: NCT06347133; SHASTA -3, NCT06347003; SHASTA-4, NCT06347016; MUIR-3, NCT06347133. FCS: PALISADE, NCT05089084; NCT05902598 | |
| Solbinsiran | DsiRNA targeting ANGPTL3 | ACS undergoing PCI: NCT06096909. Calcified aortic valve stenosis: NCT04968509 | |
| Tafolecimab | Fully human IgG2 mAb that specifically binds to PCSK9 | Before percutaneous coronary intervention in AMI: IMPROVE-AMI, NCT06683131; NCT06096909. Calcific aortic valve stenosis: NCT04968509 | |
| Zerlasiran | siRNA to inhibit Lp(a) production | High risk for atherosclerotic CV events and elevated of Lp(a): NCT05537571 | |
| Zodasiran | siRNA targeting ANGPTL3 gene expression in the liver | Mixed dyslipidaemia: ARCHES-2, NCT04832971. HoFH: GATEWAY, NCT05217667 | |
| Heart failure | Mitiperstat | Selective myeloperoxidase inhibitor | HFpEF: SATELLITE, NCT03756285; ENDEAVOR, NCT04986202 |
| CDR132L | Specific ASO, miR-132 inhibitor | HFrEF post-MI: HF-REVERT, EudraCT number: 2021-006040-27 | |
| Ponsegromab | Selective humanized anti-GDF15 mAb blocking GDF15/GFRAL signalling | HFrEF: GARDEN TIMI 74, NCT05492500 | |
| Balcinrenone | MR modulator with partial antagonist activity | Chronic HF with impaired kidney function: BalanceD-HF, NCT06307652. Balcinrenone ± dapagliflozin in patients with CKD: MIRO-CKD, NCT06350123 | |
| Ziltivekimab | Fully human mAb targeting the interleukin-6 ligand | ASCVD, CKD and inflammation: ZEUS trial, NCT05021835. CKD + Inflammation: NCT05379829. HF + inflammation: ATHENA, NCT06200207; HERMES, NCT05636176. AMI: ARTEMIS, NCT06118281 | |
| Hypertrophic cardiomyopathy | Aficamten | Cardiac myosin inhibitor | oHCM: NCT06116968; FOREST-HCM, NCT04848506; MAPLE-HCM, NCT05767346; CEDAR-HCM, NCT06412666. nHCM: ACACIA-HCM, NCT06081894 |
| BMS-986435/MYK-224 | Cardiac myosin modulator | oHCM: NCT05667493; MERCUTIO, NCT05556343. HFpEF: AURORA-HFpEF, NCT06122779 | |
| Pulmonary hypertension | AZD3427 | Relaxin agonist | HF patients and PAH Group 2: Re-PHIRE, NCT05737940 |
| Sotatercept | Fusion protein of the extracellular domain of the human activin receptor type IIA and the Fc domain of IgG1 | PAH: MOONBEAM, NCT05587712; SOTERIA, NCT04796337; ZENITH, NCT04896008; HYPERION, NCT04811092; NCT05818137. Cpc-PH due to HFpEF: CADENCE, NCT04945460. Central cardiopulmonary performance and peripheral oxygen transport during exercise in PAH: NCT06409026 | |
| Systemic hypertension | Baxdrostat | Highly selective aldosterone synthase inhibitor | Resistant hypertension: BaxHTN, NCT06034743; BaxAsia, NCT06344104; Bax24, NCT06168409. Uncontrolled hypertension + CKD: NCT05432167 |
| Zilebesiran | siRNA targeting hepatic ANG mRNA expression | Mild-to-moderate hypertension: NCT06423352. High CV risk and hypertension not adequately controlled: KARDIA-3, NCT06272487 | |
| Transthyretin-mediated amyloid cardiomyopathy | Eplontersen | Ligand-conjugated ASO to inhibit the production of hepatic TTR | EPIC-ATTR, NCT06194825; CARDIO-TTRansform, NCT04136171; NCT06465810; NCT05667493 |
| ALXN2220 | ASO that inhibits TTR | CARDIO-TTRansform, NCT06183931 | |
| NTLA-2001 | Knocking out the TTR gene | ATTR-CM, NCT06128629 |
ACS, acute coronary syndrome; AF, atrial fibrillation; AMI, acute myocardial infarction; ANG, angiotensinogen; ANGPTL3, angiopoietin-like protein-3 gene, Apo, apolipoprotein; ASCVD, atherosclerotic cardiovascular disease; ASO, antisense oligonucleotide; ATTR-CM, transthyretin-mediated amyloid cardiomyopathy; CaMKII, calcium/calmodulin-dependent protein kinase II inhibitor; CKD, chronic kidney disease; Cpc-PH, combined post-capillary and pre-capillary pulmonary hypertension; CV, cardiovascular; CVD, cardiovascular disease; DsiRNA, dicer-substrate siRNA; ESKD, end-stage kidney disease; FCS, familial chylomicronaemia syndrome; FXI, coagulation factor XI; GDF15, Growth differentiation factor 15; GFRAL, glial cell line-derived neurotrophic factor receptor alpha (GFRα)-like; GIP, glucose-dependent insulinotropic polypeptide; GLP1, glucagon-like peptide 1; GPVI, glycoprotein IV; HeFH, heterozygous familial hypercholesterolaemia; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HoFH, homozygous familial hypercholesterolaemia; HT, hypertriglyceridaemia; IgG1/2, immunoglobulin G1/G2; L(p), lipoprotein (a); LPA, lipoprotein(a) gene; mAb, monoclonal antibody; MACE, major cardiovascular events; MI, myocardial infarction; MR, mineralocorticoid receptor; mRNA, messenger RNA; NCT, National Clinical Trial; nHCM, non-obstructive hypertrophic cardiomyopathy; OAC, oral anticoagulant; oHCM, obstructive hypertrophic cardiomyopathy; PAH, pulmonary hypertension; PCI, percutaneous coronary intervention; PCSK9, proprotein convertase subtilisin/kexin type 9; siRNA, small-interfering RNA; STEMI, ST-elevation myocardial infarction; T2D, type 2 diabetes; TTR, transthyretin; VTE, venous thromboembolism.