A new PAH Treatment

Researching a new inhalable treatment for PAH

We are in the pre-clinical phases of a new paradigm for the treatment of Pulmonary Arterial Hypertension (PAH), addressing the underlying causes of the disease.

PDGF receptor inhibition: a new paradigm

We are developing a novel PDGF receptor inhibitor as an inhalation treatment for PAH. The PDGF receptor pathway has been implicated in the neointimal cell proliferation that causes obstruction to blood flow in the small blood vessels of the lung. Thus, inhibiting this pathway addresses an underlying cause of PAH. Delivering this drug by inhalation promises to improve the therapeutic window: that is to say, it should provide efficacy while avoiding systemic side effects. This project is in the lead optimization stage and moving towards IND enabling studies.

Imatinib, another PDGF receptor inhibitor showed efficacy in the IMPRES trial, a phase III clinical study. However, use of imatinib was also associated with many systemic side effects.

Pulmokine’s approach is to deliver its PDGF receptor inhibitor by inhalation, directing therapy directly to the site of the disease. Direct pulmonary delivery will result in a lower dose, and hopefully fewer side effects.

Current “step” therapies: costs and limitations

Pulmokine anticipates use of its PDGF receptor inhibitor as part of step therapy in which several drugs may be used. Many patients plateau or lose response to single agents, and require addition of a second or third medication. These vasodilators relieve symptoms without addressing the root cause. Each medication is expensive with costs ranging from $70,000 to $100,000 per year. Adverse side effects are common.

Step therapy, the current standard of practice used to treat PAH patients, consists of initial use of a PDE-V inhibitor or an endothelin receptor antagonist. In patients who do not respond, or whose response plateaus, a second oral agent may be added. Then, if a patient continues to deteriorate, the next step would be to add a prostanoid such as subcutaneous or inhaled treprostinil. Some clinicians may choose to add a prostanoid directly after limited response to a single oral agent based on the patient’s clinical course, echocardiographic estimate of RV systolic pressure, and/or surveillance right heart cath data.

Pulmokine’s PDGF receptor is a new class of drug that addresses a different aspect of the disease. Pulmokine anticipates that clinical trials will be performed in patients already on background therapy, and that its PDGF receptor inhibitor will become a new option for treating PAH.