Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension (PAH) is a progressive and incurable disease associated with widespread loss of pulmonary microvasculature, leading to increased pulmonary vascular resistance [1]. PAH is characterized by endothelial dysfunction, with the loss of endothelial vasodilating factors, such as endothelial nitric oxide synthase (eNOS), the enzyme responsible for the production nitric oxide (NO), a potent vasodilator factor that is also essential for vascular repair and angiogenesis [1]. More recently, it has been recognized that endothelial cell injury and apoptosis is central to the pathogenesis of PAH, leading directly and indirectly to the functional loss of the lung microvasculature [2]. While current treatments attempt to address endothelial dysfunction and excess vasoconstriction, most PAH patients continue to progress and eventually succumb to right heart failure [3]. Therefore, there is an unmet need for new therapies for PAH that can restore both pulmonary vascular structure and function. Northern Therapeutics has pioneered an angiogenic cell and gene therapy designed to promote repair and regeneration of the lung microcirculation that represents a first-in-class technology that is now entering phase 2 clinical trials.

PHACeT Clinical Trial

The “Pulmonary Hypertension and Angiogenic Cell Therapy trial” (PHACeT) conducted by the Company was a ‘first-in-human’ phase 1 dose-escalation study to assess the safety and efficacy of autologous endothelial progenitor cells (EPCs) transfected with human endothelial NO-synthase (eNOS) gene in patients with severe PAH refractory to available treatment. This trial showed that the study product was well tolerated with promising potential signals of improvements in functional class and exercise tolerance [1] (NCT00469027).

The SAPPHIRE Clinical Trial

The “Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension: Intervention with Repeat dosing of eNOS-enhanced EPCs” (SAPPHIRE) is a multicentre, Phase II clinical trial to establish the efficacy and safety of repeat dosing of autologous endothelial progenitor cells (EPCs) transfected with human endothelial NO-synthase (eNOS) gene in patients with PAH in addition to conventional treatments. A total of 45 participants will be enrolled in this multi-centre, Phase II, randomized, double-blind, placebo-controlled, 3-arm protocol. The trial is sponsored by Northern Therapeutics and has been registered at www.ClinicalTrials.gov (NCT03001414).