FDA Grants Orphan Drug Designation to AND017 for Sickle Cell Disease
核心洞察
The FDA has granted Orphan Drug Designation to AND017, a novel hemoglobin-elevating agent developed by Kind Pharmaceutical (搜索), for the treatment of sickle cell disease (搜索) (SCD).
AND017 targets multiple stages of the red blood cell life cycle and is being developed for various anemia (搜索) indications, including those associated with chronic kidney disease and myelodysplastic syndromes (搜索).
Clinical trial data presented at ASN Kidney Week 2024 demonstrated the safety and efficacy of AND017 in treating anemia (搜索) in both non-dialysis-dependent and dialysis-dependent chronic kidney disease patients.
The FDA has granted Orphan Drug Designation to AND017, a first-in-class hemoglobin (Hb) elevating agent developed by Kind Pharmaceutical (搜索), for the treatment of sickle cell disease (搜索) (SCD). This designation underscores the urgent need for new therapies, particularly oral drugs, to safely and effectively treat patients with SCD.
AND017: A Novel Approach to Anemia Treatment
AND017 is designed to target multiple stages of the red blood cell life cycle. Beyond SCD, it is also in development for treating anemia (搜索) associated with dialysis-dependent chronic kidney disease (DD-CKD), non-dialysis dependent chronic kidney disease (NDD-CKD), cancer-related anemia, myelodysplastic syndromes (搜索) anemia, and β-thalassemia (搜索).
Clinical Trial Data in Chronic Kidney Disease
Data from phase 1 and phase 2 trials evaluating AND017 in anemia (搜索) treatment for NDD-CKD and DD-CKD were presented at the American Society of Nephrology (ASN) Kidney Week in San Diego, October 23-27, 2024.
In a pilot multicenter, randomized, parallel-group, double-blind, dose-ranging phase 2 study (NCT05035641), 113 patients with NDD-CKD and Hb of 7.5 or higher and less than 10.0 g/dL were randomly assigned to receive various doses of AND017 (8 mg, 12 mg, or 16 mg) or placebo three times per week for five weeks. Results showed that AND017 was safe and well-tolerated. The mean rate of rise in Hb (g/dL per week) from baseline to week 6 was 1.44 g/dL, 2.03 g/dL, and 2.51 g/dL in the 8-mg, 12-mg, and 16-mg AND017 groups, respectively, compared to -0.21 g/dL in the placebo group. Cumulative response rates (Hb ≥10.0 g/dL and increase from baseline ≥1.0 g/dL during the entire treatment period) were higher in all AND017 dose and dosing frequency groups, 100% and 90% for the pooled AND017 three times per week group and once-weekly group, respectively, compared with approximately 40% in the placebo group.
Another multicenter, open-label, randomized, active-controlled phase 2 study (NCT05265325) evaluated AND017 in 175 patients with DD-CKD receiving stable hemodialysis, home hemodialysis, or peritoneal dialysis and on stable erythropoiesis-stimulating agent (ESA) treatment for at least 6 weeks. Patients were randomized to receive either 10 mg of AND017 three times per week or 16 mg once-weekly, or ESA for a 20-week period. The primary efficacy outcome was the mean change in Hb levels from baseline averaged over weeks 17 through 21. Both AND017 dose groups demonstrated similar capabilities in maintaining Hb level with ESA treatment, within the non-inferiority margin.
Potential Impact on Sickle Cell Disease Treatment
According to Gang Huang, professor at UT Health San Antonio, AND017 might provide a novel oral treatment for SCD with a unique mechanism of action and a potentially better safety and efficacy profile compared to existing treatments like hydroxyurea and L-glutamine. He expressed eagerness to see how the preclinical safety and efficacy data translate to real-world SCD patients.