Table 1.
Overview of Novel Therapeutics in Pulmonary Arterial Hypertension Under Investigation
| Treatment | Mechanism | Clinical Trial | Status or Results |
|---|---|---|---|
| Imatinib | Tyrosine kinase inhibitor; multiple targets to attenuate pro-proliferative, promigratory, and apoptosis-resistant cell behavior (not currently approved for the treatment of PAH) | IMPRES: Imatinib (QTI571) in Pulmonary Arterial Hypertension (NCT00902174) PIPAH: Positioning Imatinib for Pulmonary Arterial Hypertension (NCT04416750) |
Phase 3: Published13 Phase 2: Active; recruiting |
| Seralutinib | Tyrosine kinase inhibitor; multiple targets to attenuate pro-proliferative, promigratory, and apoptosis-resistant cell behavior with increased specificity for CSF1R and c-KIT inhibition with BMPR2 modulation | GB002 in Adult Subjects With Pulmonary Arterial Hypertension (NCT04456998) | Phase 2: Active; recruiting |
| BMP9 | Direct BMPR2 agonist | Announced, not yet enrolling | Not yet enrolling |
| Sotatercept | Activin sequestration and rebalancing of SMAD signaling leading to decreased pro-proliferative behavior | PULSAR: A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (NCT03496207) SPECTRA: A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (NCT03738150) STELLAR: A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (NCT04576988) |
Phase 2: Published31 Phase 2: Active; not recruiting Phase 3: Active; not recruiting |
| Tacrolimus | Calcineurin inhibitor; increased BMPR2-dependent SMAD 1/5 activation and transcriptional activity | Single-Center Randomized Controlled Phase II Study of Safety and Efficacy of FK-506 (Tacrolimus) in Pulmonary Arterial Hypertension (NCT01647945) | Phase 2a: Published37 Phase 2: Planned; not recruiting |
| Anastrozole | Aromatase inhibitor | PHANTOM: Pulmonary Hypertension and Anastrozole (NCT03229499) | Phase 2: Active; not recruiting |
| Tamoxifen | Estrogen receptor blocker | T3PAH: Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension (NCT03528902) | Phase 2: Active; recruiting |
| Elafin | Serine elastase inhibitor, which maintains extracellular matrix integrity | Subcutaneous Elafin in Healthy Subjects (NCT03522935) | Phase 1: Completed |
| Endothelial progenitor cells | Direct administration of endothelial nitric oxide synthase (eNOS)-enhanced endothelial cells | PHACeT: Pulmonary Hypertension: Assessment of Cell Therapy (NCT00469027) SAPPHIRE: Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension: Intervention With Repeat Dosing of eNOS-Enhanced EPCs (NCT03001414) |
Phase 1: Published64 Phase 2: Active; recruiting |
| Apabetalone | Bromodomain-containing protein 4 (BRD4) inhibitor | APPRoAcH-p: Apabetalone for Pulmonary Arterial Hypertension: A Pilot Study (NCT03655704) | Phase 1: Active; not recruiting |
| Rodatristat ethyl | Tryptophan hydroxylase inhibitor, which decreases peripheral serotonin production | ELEVATE 2: A Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension (NCT04712669) | Phase 2: Active; recruiting |
BMP9 = bone morphogenetic protein type 9; BMPR2 = bone morphogenetic protein receptor type 2; CSF1R = colony-stimulating factor 1 receptor; EPC = endothelial progenitor cell; PAH = pulmonary arterial hypertension.