Vasomera (PB1046)

Development of PB1046 (Vasomera), as an adjunctive therapy for the treatment and prevention of cardiomyopathy associated with dystrophinopathies; Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked dilated cardiomyopathy (XL-dCMP).

Lynne Georgopolous, PhaseBio Pharmaceuticals Inc.

6th December 2015

PhaseBio Pharmaceuticals Inc. proposes the development of PB1046 (Vasomera), as an adjunctive therapy for the treatment and prevention of cardiomyopathy associated with dystrophinopathies; Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked dilated cardiomyopathy (XL-dCMP). PB1046 (Vasomera) is a long-acting analog of the neuropeptide vasoactive intestinal peptide (VIP).  PB1046 has been evaluated in several heart failure animal models, which have suggested positive effects on cardiac function. Although the specific mechanisms of action are unknown, the preclinical studies have demonstrated positive lusitropy (early diastolic relaxation); improved inotropy secondary to changes in intracellular calcium mobilization; peripheral vasorelaxation, which is thought to be due to enhanced nitric oxide synthase activity; and attenuation of inflammation and fibrosis, likely due to modulation of inflammatory cell activity, based on the known mechanisms of VIP. More limited studies have been performed in the mdx mouse, and a small number of studies have been performed in the mdx:utrophin double knockout mouse.

TACT welcomes the research into cardiomyopathy in dystrophinopathy, because it is a significant cause of morbidity and mortality in patients. TACT would encourage PhaseBio to conduct further preclinical studies to support the rationale for a clinical trial of Vasomera as an adjunctive treatment for cardiomyopathy in the dystrophinopathy population. A study with similar time-points and outcome measures in mdx mice with ACEi alone, and ACEi+Vasomera treatment groups compared with untreated mdx mice was also suggested. TACT recommended that the potential for the production of antibodies should be a focus of the upcoming clinical studies; and that consideration should be given to limiting the study to a much more clinically homogenous population, such as DMD patients or BMD patients with a similar degree of skeletal and cardiac muscle impairment.

 
12 Apr 2017