Oral AND017 granted orphan drug status for SCD
Preclinical trials show treatment safe, works as intended
The U.S. Food and Drug Administration has granted orphan drug status to Kind Pharmaceuticals’ investigational oral small molecule AND017 to treat sickle cell disease (SCD).
This designation is granted to potential treatments for rare diseases, or those affecting fewer than 200,000 people in the U.S. It provides incentives like tax credits for clinical trials, exemption from certain fees, and seven years of market exclusivity if an approval is ultimately granted.
“The FDA’s granting of ODD [orphan drug designation] for AND017 underscores the urgent medical need for new therapies, particularly oral drugs to safely and effectively treat patients with SCD,” Dong Liu, PhD, Kind’s founder, chairman, and CEO, said in a company press release.
SCD results from mutations in the gene coding for hemoglobin, a protein that carries oxygen in red blood cells. The mutated protein causes red blood cells to take on a sickle-like shape. These misshapen red blood cells block small blood vessels, leading to organ damage and painful episodes known as vaso-occlusive crises. They are also prone to break down easily, causing anemia.
AND017 inhibits an oxygen-sensitive enzyme called hypoxia-inducible factor prolyl hydroxylase (HIF-PH). This tricks the body into thinking that oxygen levels are falling below normal levels, which signals the bone marrow to produce more red blood cells.
Better safety, efficacy
In preclinical studies, AND017 appeared to be safe and work as intended. For Gang Huang, PhD, a professor at the University of Texas Health San Antonio who was involved in those studies, AND017 “might not only provide a novel oral treatment with unique mechanism of action, but also an obvious better safety and efficacy profile.”
“Hydroxyurea and L-glutamine [marketed as Endari] are the limited FDA-approved oral treatments for SCD,” Huang said. “I am eager to see how a compound with such unbelievable preclinical safety and efficacy data will translate to real world SCD patients.”
Because AND017 triggers the production of red blood cells, it is also being developed to treat anemia due to other conditions, including chronic kidney disease, cancer, myelodysplastic syndrome, and beta-thalassemia, another disease marked by reduced levels of hemoglobin.
AND017 has been tested in two Phase 1 studies in healthy volunteers: one in Australia (NCT04751539) that evaluated multiple doses of the therapy a single time or once daily for 10 days, and another in China (NCT04712500), which examined whether the oral therapy can be taken with food.
In the Australian study, AND017 showed safe, predictable behavior in the body across single and multiple doses, with elimination half-lives (the time taken for its levels to halve) from 10.1 to 19.7 hours. In the study in China, food did not affect the levels of AND017, indicating the treatment can be taken with or without food.
Two Phase 2 studies (NCT05035641 and NCT05265325) have also investigated it in people with chronic kidney disease at sites in the U.S. and China. In both studies, treatment with AND017 increased or maintained the levels of hemoglobin in the blood and was well tolerated.
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