The American Society for Bone and Mineral Research (ASBMR) and Rare Bone Disease Alliance (RBDA) held the annual Symposium on Rare Bone Diseases this year on October 12. During the Symposium, patients, clinicians, and scientists came together to discuss patient needs and the latest scientific and clinical advancements. According to a news release, AM-Pharma presented at the conference and discussed positive clinical results from a Phase 1b clinical trial which explored ilofotase alfa as a potential enzyme replacement therapy (ERT) for adults living with hypophosphatasia.
What is Hypophosphatasia (HPP)?
Hypophosphatasia is a rare genetic disorder characterized by impaired bone and teeth calcification. Caused by a variety of ALPL gene mutations, and inheritance patterns, hypophosphatasia prevents bones and teeth from retaining calcium and phosphorus. This means that bones and teeth are often soft and prone to fractures, breakage, or loss. Hypophosphatasia seems more common in Mennonite communities. Symptoms may include early loss of baby teeth, bowed long bones, skeletal abnormalities, anemia, emphysema, a large fontanelle in infants, high blood calcium levels, failure to thrive, recurrent vomiting and kidney problems in infants, hypotonia, frequent fractures, and seizures.
Although there are treatments available, researchers believe that we need to expand the treatment landscape.
What the Study Findings Show
Ilofotase alfa is a recombinant alkaline phosphatase enzyme that reduces inflammation, protects against kidney damage, and addresses biomarkers relating to pain and bone mineralization. It has been granted Orphan Drug designation in both the United States and European Union for hypophosphatasia. Preclinical studies found that ilofotase alfa improved overall survival rates.
Within the Phase 1b study, researchers explored varying doses of ilofotase alfa in 12 people living with HPP. Trial participants either received 0.8mg/kg or 3.2mg/kg of intravenously administered ilofotase alfa.
After 10 days, participants had lower pyridoxal-5′-phosphate (PLP) and inorganic pyrophosphate (PPi) levels, which correlate to pain and bone mineralization. PLP dropped by 35% and 66% respectively, and PPi by 36% and 77% respectively. This highlighted how ilofotase alfa could improve overall health and bone strength in HPP. The treatment was also safe and well-tolerated by participants.
