The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to Kind Pharmaceuticals' investigational oral small molecule, AND017, for the treatment of sickle cell disease (SCD). This designation aims to incentivize the development of therapies for rare diseases affecting fewer than 200,000 people in the U.S., offering benefits such as tax credits for clinical trials, exemption from certain fees, and seven years of market exclusivity upon approval.
Dong Liu, PhD, Kind's founder, chairman, and CEO, stated that the FDA's decision underscores the urgent need for new, effective, and safe therapies, particularly oral drugs, for SCD patients.
Mechanism of Action and Preclinical Data
SCD is caused by mutations in the hemoglobin gene, leading to misshapen red blood cells that obstruct small blood vessels, causing organ damage, vaso-occlusive crises, and anemia. AND017 functions by inhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which simulates low oxygen levels in the body. This, in turn, stimulates the bone marrow to produce more red blood cells.
Preclinical studies have suggested that AND017 has a favorable safety profile and works as intended. Gang Huang, PhD, a professor at the University of Texas Health San Antonio, noted that AND017 could provide a novel oral treatment with a unique mechanism of action and potentially better safety and efficacy compared to existing treatments like hydroxyurea and L-glutamine (Endari).
Clinical Development and Ongoing Trials
AND017 has undergone evaluation in two Phase 1 studies involving healthy volunteers. An Australian study (NCT04751539) assessed multiple doses of AND017, both single and once-daily for 10 days, revealing safe and predictable behavior with elimination half-lives ranging from 10.1 to 19.7 hours. A Chinese study (NCT04712500) examined the effect of food on AND017 levels, demonstrating that food does not affect its absorption, allowing for administration with or without meals.
Furthermore, AND017 is being investigated in two Phase 2 studies (NCT05035641 and NCT05265325) in individuals with chronic kidney disease across sites in the U.S. and China. Preliminary results indicate that AND017 treatment increased or maintained hemoglobin levels and was well tolerated in these patients. The company is also exploring AND017's potential in treating anemia associated with other conditions, including cancer, myelodysplastic syndrome, and beta-thalassemia.
