Pfizer has discontinued its phase 2 pulmonary arterial hypertension (PAH) program involving PF-07868489, an experimental treatment developed to inhibit bone morphogenetic protein 9 (BMP9). The company attributed the decision to business reasons rather than safety or efficacy concerns. The termination was disclosed in Pfizer’s third-quarter financial update, which also detailed the discontinuation of several other clinical development programs.
Development of the PAH Candidate
PF-07868489 emerged from research findings indicating that inhibiting BMP9 could protect rodents against PAH. Pfizer had initially investigated approaches designed to activate the protein but subsequently shifted towards studying antagonists as evidence of the potential benefits of BMP9 inhibition emerged.
The company began a phase 1/2 trial of PF-07868489 in 2023 and initiated a phase 2 open-label extension study in 2025. The extension was intended to continue the investigation of the candidate, but Pfizer terminated the study approximately one year after its launch.
The study had been scheduled to conclude in the second half of 2028. Pfizer’s decision to end it was based on business considerations, rather than concerns about the candidate’s safety or effectiveness.
Additional Discontinuation in Autoimmune Disease Research
PF-07868489 was one of two mid-stage drug development programs removed from Pfizer’s portfolio in its third-quarter update. The other was PF-06835375, an experimental treatment targeting CXCR5 that had been investigated for autoimmune diseases.
Pfizer had previously stopped a phase 2 trial of PF-06835375 in primary immune thrombocytopenia (ITP) before its planned completion. The company attributed that decision to business reasons. Its subsequent pipeline update also removed the ITP program and a phase 1 assessment of PF-06835375 in lupus.
Changes to Obesity Drug Development
Pfizer also discontinued four other phase 1 programs during the quarterly pipeline review, including two involving obesity and chronic weight management.
One was PF-07999415, an experimental obesity candidate directed at an undisclosed target. The drug entered clinical testing in 2025 before Pfizer ended its development.
The company also discontinued a phase 1 trial testing two assets acquired from Metsera: PF-08654696, a glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist, and PF-08653944, a glucagon-like peptide-1 (GLP-1) receptor agonist.
Pfizer continues to evaluate PF-08653944 in other settings. However, the discontinued combination study was the only active clinical trial involving PF-08654696.
The decision followed Pfizer’s discontinuation of PF-07976016, a GIPR antagonist, three months earlier. Research has indicated that both activating and blocking GIPR can reduce body weight. Eli Lilly’s tirzepatide activates the receptor, while Amgen’s MariTide blocks it.
KRAS Inhibitor Trials Discontinued
The pipeline changes also included two selective KRAS inhibitors, PF-07985045 and PF-07934040, which entered phase 1 trials for solid tumors in 2024.
Pfizer terminated the PF-07985045 study in May but continued listing the program as active in its second-quarter financial update. In July, the company stopped enrollment in the PF-07934040 trial before it reached its recruitment target.
The third-quarter update detailed these changes across Pfizer’s PAH, autoimmune disease, obesity, and solid tumor research programs.
Pfizer Ends Development of Its Phase 2 PAH Candidate
Pfizer has ended development of its Phase 2 pulmonary arterial hypertension program involving investigational candidate PF-07868489. The decision was linked to business considerations rather than safety or efficacy concerns, according to the clinical trial record. The terminated open-label extension study had enrolled 42 participants and was designed to examine the long-term safety and effects of the treatment. app.readthrough.bio
Impact on Pulmonary Arterial Hypertension Research
The decision to end the Phase 2 program highlights the difficult and highly selective nature of drug development. Clinical research requires significant investment, long-term planning, and careful evaluation of scientific and commercial priorities. Even promising programs can be discontinued when companies decide to redirect resources toward other therapeutic areas or development opportunities.
Pulmonary arterial hypertension remains a serious and complex disease with a need for continued innovation. Patients may experience progressive limitations in physical activity as the condition places increased pressure on the heart and lungs. Researchers continue to explore new treatment approaches that could improve disease management and long-term outcomes.
The conclusion of this program may also influence how pharmaceutical companies evaluate future opportunities in cardiovascular and rare disease research. Developers are increasingly using advanced clinical data, biomarkers, and precision medicine approaches to identify patient populations that may benefit most from new therapies.
Competition in the pulmonary hypertension treatment landscape continues to encourage innovation. Established therapies and emerging drug candidates are being studied across different biological pathways, creating opportunities for new combinations and targeted approaches.
