Valerion Therapeutics said today that the company developed a fusion protein, VAL-1221, that combines its antibody delivery system with recombinant human acid alpha-glucosidase (rhGAA) to better deliver rhGAA into affected tissues of patients with Pompe disease.
Patients who suffer from Pompe disease have a deficient supply of the lysosomal enzyme, GAA, which causes glycogen to accumulate in cardiac and skeletal muscles. Although researchers have observed that glycogen accumulates in both lysosomes and cytoplasm of Pompe disease patients, the currently-approved enzyme-replacement therapy only clears glycogen in the lysosome.
Researchers at Duke University demonstrated that Valerion’s antibody-mediated enzyme-replacement therapy is effective in cultured Pompe patient fibroblasts and in Pompe GAA-deficient mice.
VAL-1221 cleared away lysosomal glycogen as effectively as current enzyme-replacement therapy, according to the study results, and also penetrated living cells independent of the cell entry mechanism associated with current treatment methods. The team of researchers suggested that VAL-1221’s delivery mechanism could be better than traditional therapies because it clears both lysosomal and cytoplasmic glycogen.
“We believe our findings are a game-changer in the treatment of Pompe disease,” CEO Deborah Ramsdell said in prepared remarks. “We are excited about the potential to help patients who are looking for alternatives to the current approved therapy.”
The Concord, Mass.-based company plans to initiate a clinical trial in the U.S. and the UK next month to evaluate its VAL-1221 therapy in patients with late-onset Pompe disease.
The randomized, dose-escalation trial will study the treatment’s safety, tolerability and preliminary efficacy in ambulatory and ventilator-free patients. Valerion said it expects top line results later this year.
“The approach is different from other ERT approaches as this has the ability to act on glycogen in the cytoplasm. This remains a challenge in the field of Pompe disease,” principal investigator Dr. Priya Kishnani added. “Glycogen that is leached out (either due to shearing effect or rupture of lysosomes) into cytoplasm needs to be cleared. The collaboration with Valerion is an important one as it allows us to look at whether VAL-1221 has this additional benefit.”
