FDA Grants Orphan Drug Designation to ABBV-CLS-628 for ADPKD

The US Food and Drug Administration (FDA) has granted Orphan Drug Designation to ABBV-CLS-628, an investigational therapy for the treatment of autosomal dominant polycystic kidney disease (ADPKD).1

Announced on November 5, 2025, by parent company Calico Life Sciences, the designation stems from the ongoing phase 2, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of intravenous ABBV-CLS-628 in adults with ADPKD.1

"We are pleased that ABBV-CLS-628 has received both Fast Track and Orphan Drug designations, underscoring the urgent unmet need facing the ADPKD community," Arthur D. Levinson, PhD, CEO of Calico, said in a statement. "People living with this disease face a high risk of rapid disease progression, and we will continue to advance this program with the goal of improving the treatment trajectory for patients."1

ADPKD is a progressive disease characterized by the development and growth of fluid-filled cysts in the kidneys and is the most common inherited kidney disease worldwide. By age 60, ADPKD leads to kidney failure in more than 50% of patients, with dialysis or transplant as the only remaining treatment options. The disease is associated with dysregulated insulin-like growth factor (IGF) signaling due to high expression of the pregnancy-associated plasma protein-A (PAPP-A).1,2,3

ABBV-CLS-628, an anti-PAPP-A monoclonal antibody, is designed to target cyst growth directly. Other therapies, such as tolvaptan, act by reducing fluid accumulation through vasopressin signaling and do not directly target cyst expansion. While successfully slowing the increase of total kidney volume and decline in kidney function, patients reported adverse effects and higher discontinuation rates. By inhibiting the PAPP-A enzyme to reduce IGF, the treatment may slow cyst formation and kidney enlargement.2,4

A prior randomized, double-blind, placebo-controlled, first-in-human phase 1 trial was conducted to assess the safety, tolerability, and pharmacokinetics of ABBV-CLS-628. The study enrolled 138 participants with a diagnosis of ADPKD aged >18 to <65 years of age. Trial results demonstrated general efficacy and safety, showing no significant adverse effects in patients.2,3,5

ABBV-CLS-628 was previously granted Fast Track Designation by the FDA on October 2, 2025, underscoring the importance of developing new therapies to slow disease progression in ADPKD patients and prevent eventual kidney failure.5

“We are pleased that ABBV-CLS-628 has been granted Fast Track Designation. This recognition reflects the significant unmet need facing the ADPKD community and the potential of ABBV-CLS-628 to slow kidney function decline in patients with a high risk of rapidly progressing disease,” said Levinson in a previous statement. “With limited treatment options available, we are hopeful that this therapy may ultimately provide patients with much-needed treatment options.”5

The ongoing phase 2 trial is enrolling approximately 240 adult participants with ADPKD, defined as estimated glomerular filtration rate (eGFR) between >30 mL/min/1.73m2 and <90 mL/min/1.73m2 at >95 global sites. The trial will compare intravenous ABBV-CLS-628 administered every 4 weeks with a placebo. The study duration is 92 weeks, with a 15-week safety follow-up period. Key endpoints include changes in total kidney volume, eGFR decline, and safety outcomes. Secondary measures will evaluate patient quality of life, biomarker responses, and treatment tolerability.6

References

1. Calico. Calico Life Sciences Announces U.S. FDA Orphan Drug Designation for Investigational Treatment of Autosomal Dominant Polycystic Kidney Disease. Prnewswire.com. Published November 5, 2025. Accessed November 5, 2025. https://www.prnewswire.com/news-releases/calico-life-sciences-announces-us-fda-orphan-drug-designation-for-investigational-treatment-of-autosomal-dominant-polycystic-kidney-disease-302604924.html

2. Horton M, Hajian H, Desai JM, et al. #3568 Safety and tolerability of ABBV-CLS-628: Results from a phase 1 first-in-human study. Nephrology Dialysis Transplantation. 2025;40(Supplement_3). https://doi.org/10.1093/ndt/gfaf116.0473

3. Kashyap S, Kyaw Zaw Hein, Claudia C.S. Chini, et al. Metalloproteinase PAPP-A regulation of IGF-1 contributes to polycystic kidney disease pathogenesis. JCI insight. 2020;5(4). https://doi.org/10.1172/jci.insight.135700.

4. Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease. New England Journal of Medicine. 2012;367(25):2407-2418. https://doi.org/10.1056/nejmoa1205511.

5. Calico Life Sciences Announces U.S. FDA Fast Track Designation for Investigational Treatment of Autosomal Dominant Polycystic Kidney Disease - Calico. Calico. Published October 2, 2025. Accessed November 5, 2025. https://www.calicolabs.com/press/calico-life-sciences-announces-u-s-fda-fast-track-designation-for-investigational-treatment-of-autosomal-dominant-polycystic-kidney-disease/

6. A Study to Assess Adverse Events and Effectiveness of IntraVenous Infusions of ABBV-CLS-628 in Adult Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) | PKD Clinical Studies. PKD Clinical Studies. Published September 16, 2025. Accessed November 5, 2025. https://clinicalstudies.pkdcure.org/study/abbvie-clinical-trial/