US-based BioMarin Pharmaceutical has dosed the first patient in a Phase III INSPIRE trial of BMN 701, a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), for treatment of Pompe disease, an inherited condition caused by a deficiency in the lysosomal enzyme acid alpha glucosidase.
BMN 701 (GILT-tagged Recombinant Human GAA) is designed to target delivery to the lysosomes where the enzyme is most needed.
The single-arm, open-label, switchover Phase III INSPIRE trial is designed to evaluate if patients who have been taking rhGAA (recombinant human acid alglucosidase alfa) can realise further improvement in measures of respiratory muscle strength and endurance.
The trial is also aimed at better understanding the safety effects when switching therapies from rhGAA to BMN 701.
The Phase III trial is focused on late-onset Pompe disease, which can lead to progressive weakening of the muscles of the body, including the diaphragm, a crucial respiratory muscle.
The company said that respiratory impairment is the leading cause of morbidity and mortality in late onset Pompe disease.
BioMarin chief medical officer Hank Fuchs said most patients with Pompe disease suffer breathing problems related to respiratory weakness, and many will eventually require respiratory support, such as a ventilator.
"In the Phase III INSPIRE trial, we hope to see improvements in respiratory muscle weakness, which is one of the hallmarks of Pompe disease," Fuchs said.
"We hope that treatment with BMN 701 will be well-tolerated and that it could benefit patients by potentially helping them breathe easier and reducing the need for mechanical breathing assistance and increasing endurance."
According to the company, research has showed that over time, Pompe patients experience a progressive decrease in clinical measures of respiratory function, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP).
BioMarin chief executive officer Jean-Jacques Bienaimé said the development of BMN 701 is another opportunity for the company to leverage its clinical and regulatory experience and manufacturing know-how.
"There is a significant amount of interest in the medical and Pompe patient communities for more treatment options for late-onset Pompe disease," Bienaimé said.
"We believe, based on our studies to date, that BMN 701 has the potential to deliver more of the enzyme to muscle lysosomes compared to the currently available option."
Initially, the safety and efficacy of BMN 701 was evaluated in a 24-week, open-label Phase I/II trial of 22 treatment naïve, late-onset Pompe patients 13 years of age and older.