ALIGN SUBGROUP ANALYSES: CLINICALLY MEANINGFUL UPCR REDUCTIONS SEEN ACROSS SUBGROUPS

Introduction:

Approximately 30% of IgAN patients with proteinuria 1–2 g/day develop kidney failure within 10 years; even patients with low levels of persistent proteinuria (<1 g/day) are at risk. Endothelin (ET)-1 upregulation and ETA receptor activation drive proteinuria, kidney inflammation and fibrosis in IgAN. Atrasentan is a potent and selective ETA receptor antagonist. ALIGN is a Phase 3, randomized, double-blind, placebo-controlled study of the efficacy and safety of atrasentan vs placebo in adult IgAN patients on optimized supportive care.

Methods:

Patients with biopsy-proven IgAN and proteinuria of ≥1 g/day were randomized to receive atrasentan 0.75 mg or placebo orally once daily for 132 weeks while continuing supportive care. The primary endpoint, the change from baseline in proteinuria at Week 36, based on UPCR from 24-hour urine collection was evaluated in a prespecified interim analysis of the first 270/340 patients randomized to the main stratum. Subgroups evaluated included key demographic (gender, age, race, ethnicity and region), and baseline disease characteristics (baseline UPCR, BP, eGFR and diuretic use).

Results:

 The prespecified interim analysis of the primary endpoint showed a 36.1% (26.4%, 44.6%; p<0.0001) relative reduction in LS mean % UPCR change from baseline at Week 36.  Proteinuria reduction was of similar magnitude regardless of age, sex, race, ethnicity or region, and baseline levels of proteinuria, eGFR, BP or diuretic usage (Figure). Atrasentan was well-tolerated with a favorable safety profile. Results for an exploratory SGLT2i stratum were consistent with the main stratum.

Conclusions:

Clinically meaningful proteinuria reductions were observed with atrasentan in all subgroups regardless of baseline demographic or disease characteristics.

This abstract was also submitted for the ASN Kidney Week 2024: Heerspink HH, et al. ALIGN subgroup analyses: clinically meaningful UPCR reductions seen across subgroups [Abstract FR-OR62].

I have potential conflict of interest to disclose.
This analysis was funded by Novartis Pharma AG. HJLH: consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, Dimerix, Eli Lilly, Gilead, Janssen, Merck, Novartis, Novo Nordisk, Roche, and Travere Therapeutics; research support: AstraZeneca, Boehringer Ingelheim, Janssen, and Novo Nordisk; honoraria from AstraZeneca and Novo Nordisk; travel expenses from Eli Lilly. M.J.J. is responsible for research projects that have received funding from Amgen, Baxter, CSL, Dimerix, Eli Lilly, Gambro, Kensana and MSD; has received fees for Advisory, Steering Committee and/or Scientific Presentations from Akebia, Amgen, Astra Zeneca, Baxter, Bayer, Boehringer Ingelheim, Cesas Medical, Chinook, CSL, Janssen, Medcon International, Medscape, MSD, NovoNordisk, Occurx, Roche and Vifor; with any consultancy, honoraria or travel support directed to her institution.  DEK: consulting fees from AstraZeneca, Chinook Therapeutics, and Travere Therapeutics, and honoraria from Chinook Therapeutics and Travere Therapeutics. RAL: fees from Alexion, AlpineBio, Aurinia, Beigene, ChemoCentryx/Amgen, Calliditas, HiBio, Novartis, Omeros, Otsuka, Roche, Travere and Vera Therapeutics; research funding from Apellis, Calliditas, Chinook, Genentech, NIH, Omeros, Otsuka, Roche, Travere and Vera therapeutics. A. Levin reports being a member of a steering committee for Chinook/Novartis. A. Liew reports employment with The Kidney & Transplant Practice Pte Ltd; consultancy for Alexion Pharmaceuticals, Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, AstraZeneca, Baxter Healthcare, Bayer AG, BioCryst Pharmaceuticals, Boehringer-Ingelheim, Chinook Therapeutics, Dimerix Limited, Eledon Pharmaceuticals, Fresenius Medical Care, George Clinical, GlaxoSmithKline, Kira Pharmaceuticals, Prokidney, Otsuka Pharmaceuticals, Vera Therapeutics, Visterra Inc, Zai Lab Co. Ltd; has received speaker's honorarium from AstraZeneca, BaxterHealthcare, Boehringer-Ingelheim, Chinook Therapeutics, Fresenius Medical Care, Otsuka Pharmaceuticals, Vera Therapeutics; and has served as a member of Data Safety and Monitoring Committee for Dimerix Limited and Zai Lab Co. Ltd. HZ: employee of Peking University First Hospital; consultancy fees for being a Steering Committee member from Calliditas, Chinook, Novartis, Omeros, and Otsuka; participated in symposia or panel discussions and received honoraria for scientific presentations from Novartis and Omeros. TG, KS and HK are employees/ ex-employees of Chinook, a Novartis company. RR is an employee of Novartis. JB reports: consulting and speaker fees from Alnylam, Argenx, Astellas, BioCryst, Calliditas, Chinook, Dimerix, Galapagos, Novartis, Omeros, Travere Therapeutics, Vera Therapeutics, Visterra; grant support from Argenx, Calliditas, Chinook, Galapagos, GlaxoSmithKline, Novartis, Omeros, Travere Therapeutics, Visterra; research projects: Argenx, Calliditas, Chinook, Galapagos, GlaxoSmithKline, Novartis, Omeros, TravereTherapeutics, Visterra; and clinical trials: ADU-CL-19 & ALIGN (Chinook), APPLAUSE (Novartis), ARTEMIS-IGAN (Omeros), ENVISION (Visterra), NefIgARD (Calliditas), ORIGIN (Vera Therapeutics).

I did not use generative AI and AI-assisted technologies in the writing process.