A Phase I, open label, dose escalation study to assess the safety and pharmacodynamics of IV administration of three escalating doses of PLX-PAD cells in subjects with symptomatic Pulmonary Arterial Hypertension (PAH) was initiated by United Therapeutics. There were 3 planned dose cohorts, and each cohort was to enroll three subjects. Each subject was to receive a single dose of either 0.5 million cells/kg of body weight, 1.0 million cells/kg, or 2.0 million cells/kg. Safety was the primary endpoint, and secondary objectives were to evaluate the impact of those 3 escalating doses at 6 weeks post-treatment on multiple measures, including 6-minute walking distance (6MWD) and cardiac hemodynamic parameters.
Data from the first cohort of three patients given PLX-PAD demonstrated a good safety profile and an encouraging, albeit limited, efficacy trend: initial findings from cohort 1 suggest an average improvement of 21 meters from baseline in the six-minute walk distance (6MWD) at 3-month follow up. The two patients with Grade 2 (moderate) PAH had an average improvement of 40 meters in 6MWD. There were no specific safety concerns, and no discontinuations due to adverse events during the study.
This indication was being developed under a licensing agreement with United Therapeutics Corporation. In December, 2015, United Therapeutics ended its licensing agreement with Pluristem for the development of PLX-PAD for the treatment of PAH. Pluristem regained full rights to PLX-PAD in this indication, as well as all clinical data and regulatory submissions, allowing Pluristem to move forward with the clinical development of the program and seek other licensing partners.