FDA Grants Orphan Drug and Rare Pediatric Disease Designations to HKBU's Aptamer for X-Linked Hypophosphatemia
Key Insights
An aptamer developed by Hong Kong Baptist University (HKBU) for treating X-linked hypophosphatemia (search) (XLH (search)) has received Orphan Drug Designation from the FDA.
The FDA also granted the aptamer a Rare Pediatric Disease Designation, potentially accelerating its clinical translation and benefiting XLH (search) patients.
Preclinical studies suggest the aptamer, Apc001, can promote bone formation and increase blood phosphorus levels without increasing cardiovascular risk.
Hong Kong Baptist University (HKBU) and the Shanghai Sixth People's Hospital (search) have announced that their jointly developed aptamer, Apc001, for the treatment of X-linked hypophosphatemia (search) (XLH (search)), has been granted both Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration (FDA). This aptamer, initially designed for osteogenesis imperfecta (search), targets the sclerostin-loop3 (search) domain and has shown promise in preclinical studies.
XLH (search) is a rare, inherited bone disease characterized by hypophosphatemia, resulting from mutations in the PHEX gene. This leads to impaired bone mineralization, causing skeletal deformities, growth retardation in children, and osteomalacia in adults. Current treatments have limitations, creating an unmet need for more targeted therapies.
Targeting Sclerostin Loop3 Domain
Researchers, including Professor Zhang Ge from HKBU and Professor Zhang Zhenlin from Shanghai Sixth People's Hospital (search), discovered that XLH (search) patients exhibit elevated serum sclerostin (search) levels, approximately 4.5 times higher than healthy individuals. While sclerostin antibodies exist, they carry cardiovascular risks. The team found that the "loop3 domain" of sclerostin is crucial for inhibiting bone formation but not for cardiovascular protection. Therefore, selectively targeting this domain could promote bone growth without increasing cardiovascular risk.
Apc001: A Novel Therapeutic Approach
Apc001, an oligonucleotide aptamer, was developed to specifically inhibit the sclerostin (search) loop3. Animal studies demonstrated that Apc001 effectively promotes bone formation and significantly increases blood phosphorus levels in XLH (search) model mice, suggesting its potential as a targeted therapy for XLH patients.
Regulatory Advantages and Clinical Development
The FDA's Orphan Drug Designation provides several benefits, including reduced clinical trial sample sizes, exemption from new drug marketing authorization fees, and seven years of market exclusivity. The Rare Pediatric Disease Designation allows for priority review. These designations are expected to expedite the clinical translation of Apc001.
Pilot scale production of Apc001 has been completed, and preclinical toxicological assessments are underway. Clinical trials are planned in both Mainland China and the U.S., marking a significant step toward a new treatment option for XLH (search) patients.