FDA Grants Orphan Drug Designation to AND017 for the Treatment of Sickle Cell Disease

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The FDA granted an orphan drug designation (ODD) to AND017 (Kind Pharmaceutical) for the treatment of sickle cell disease (SCD). The preclinical work that supports the ODD for AND017 in SCD will be presented in future scientific meetings and published in journals, according to experts. In addition, findings from phase 1 and phase 2 trials evaluating AND017 in the treatment of anemia in non-dialysis dependent chronic kidney disease (NDD-CKD) in dialysis-dependent chronic kidney disease (DD-CKD) were presented at the annual meeting of American Society of Nephrology (ASN) Kidney Week at San Diego, which was held October 23 to 27, 2024.¹

"The FDA's granting of ODD for AND017 underscores the urgent medical need for new therapies, particularly oral drugs to safely and effectively treat patients with SCD," Dong Liu, PhD, founder, chairman, and CEO of Kind Pharmaceutical, said in a news release.¹

AND017 is a first-in-class hemoglobin (Hb) elevating agent that targets multiple stages of the red blood cell life cycle, and in addition to treating anemia associated with DD-CKD and NDD-CKD, it is also in development to treat cancer-related anemia, myelodysplastic syndromes anemia, SCD, and β-thalassemia. Currently, the agent is in development to treat various anemia indications associated with diseases including NDD-CKD and DD-CKD.¹

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, including 8 mg (n = 28), 12 mg (n = 29), 16 mg (n = 28), or placebo (n = 28) 3 times per week during the first 5 weeks of treatment. At the end of week 6, patients who met pre-defined criteria were randomly assigned again to either continue the 3 times per week dosing schedule, or switch to a once-weekly dosing schedule and enter an 8-week titration period. During this period, doses of the study drug were adjusted to maintain Hb within the range of 10.0 to 11.0 g/dL.^2,3

Overall, AND017 was found to be safe and well-tolerated in patients with NDD-CKD and anemia. Compared with the placebo group, 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, 2.51 g/dL in the 8-mg, 12-mg, and 16-mg AND017 groups, respectively (placebo: -0.21 g/dL). In addition, 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 3 times per week group and once-weekly group, respectively, compared with approximately 40% in the placebo group.³

In addition, treatment-emergent adverse events (AEs) occurred in approximately 69.41% of patients in the pooled AND017 group compared with 64.29% in the placebo group, whereas treatment-related AEs occurred in 11.76% in the pooled AND017 group compared with 3.57% in the placebo group. A total of 6 patients from the AND017 dose groups experienced serious AEs, but these were not found to be related to the study drug.³

Further, a 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 randomly assigned to receive either 10 mg of AND017 3 times per week (n = 59) or 16 mg once-weekly (n = 57) and were treated, or ESA (n = 59) for a 20-week period. Dose adjustments were allowed for both AND017 and ESA in the study to maintain Hb levels within the target range (US: 10.0-11.0 g/dL; China: 10.0-12.0 g/dL).^4,5

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.⁵

Additionally, treatment-emergent AEs occurred in approximately 81.4% of patients in the 10-mg AND017 group, 75.4% in the 160mg AND017 group, and 66.1% in the ESA group. Treatment-related AEs were reported in approximately 6.8%, 10.5%, and 3.4% of patients, respectively. A total of 48 patients reported experiencing serious AEs, with approximately 32.2% in the AND017 10-mg 3 times per week group, 28.2% in the AND017 16-mg once-weekly group, and 22.0% in the ESA group; however, none were considered to be associated with the study drug or active control, according to the investigators.⁵

"Hydroxyurea and L-glutamine are the limited FDA-approved oral treatments for SCD, AND017…might not only provide a novel oral treatment with unique mechanism of action, but also an obvious better safety and efficacy profile," Gang Huang, professor at UT Health San Antonio and Kathryn Mays Johnson distinguished chair in oncology, said in the news release. "I am eager to see how a compound with such unbelievable preclinical safety and efficacy data will translate to real-world SCD patients."¹

REFERENCES

1. PR Newswire. KIND Announces FDA Granted Orphan Drug Designation (ODD) for AND017 in the Treatment of Sickle Cell Disease (SCD). News release. October 25, 2024. Accessed October 25, 2024. https://prnmedia.prnewswire.com/news-releases/kind-announces-fda-granted-orphan-drug-designation-odd-for-and017-in-the-treatment-of-sickle-cell-disease-scd-302287483.html

2. A Study of AND017 to Treat Anemia in Non-dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients. ClinicalTrials.gov identifier: NCT05035641. Updated October 4, 2023. Accessed October 25, 2024. https://clinicaltrials.gov/study/NCT05035641

3. Zhu Y, Zuo L, Ding X, et al. Abstract: TH-PO898—Safety and Efficacy of AND017, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), in Patients with Nondialysis-Dependent CKD (NDD-CKD). Presented at: American Society of Nephrology (ASN) Kidney Week 2024. San Diego, California. October 23-27, 2024. https://www.asn-online.org/education/kidneyweek/2024/program-abstract.aspx?controlId=4124344

4. A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis. ClinicalTrials.gov identifier: NCT05265325. Updated June 28, 2024. Accessed October 25, 2024. https://clinicaltrials.gov/study/NCT05265325

5. Zhu Y, Ding X, Wilson S, et al. Abstract: TH-PO1181—Efficacy and Safety of AND017 for Treatment of Anemia in Dialysis-Dependent CKD. Presented at: American Society of Nephrology (ASN) Kidney Week 2024. San Diego, California. October 23-27, 2024. https://www.asn-online.org/education/kidneyweek/2024/program-abstract.aspx?controlId=4124344