Zigakibart

Novartis hopes to repeat the risky regulatory path of its competitor Travere Therapeutics after its phase 3 trial of its IgAN drug missed statistical significance on a kidney function endpoint. It’s déjà vu all over again. Just as the kidney disease space becomes increasingly competitive, Novartis has found itself intending to turn a statistical miss into a regulatory win.Despite the phase 3 Align trial narrowly failing to hit its kidney function endpoint, Novartis announced Friday that it will pursue traditional FDA approval for Vanrafia (atrasentan) in IgA nephropathy (IgAN).The Swiss pharma wouldn’t be the first to try to convince the FDA of a full IgAN nod following a phase 3 kidney function miss. Travere’s Protect phase 3 trial had previously failed to show a statistically significant advantage for Filspari on kidney function as measured by the estimated glomerular filtration rate (eGFR) after two years. But the FDA still converted Filspari’s accelerated approval in IgAN into a full nod in 2024. For its part, Novartis is leaning on a “positive difference” with Vanrafia versus placebo in eGFR change from baseline at Week 136, as well as a “clinically meaningful” improvement for the drug at Week 132, when study treatment ended. The difference at Week 136, a key secondary endpoint of the Align trial, arrived at 2.39ml/min/1.73m2, with a p-value of 0.057 that missed statistical significance. At Week 132, the difference in eGFR change was 2.59ml/min/1.73m2, with a nominal p-value of 0.039, Novartis said Friday. “Progressive and complex diseases such as IgAN present an urgent need for medicines that can target the different drivers of the disease. Vanrafia can be seamlessly integrated into patients’ existing treatment plans, with a consistent safety profile,” Ruchira Glaser, M.D., Novartis’ global head of cardiovascular, renal and metabolic development, said in a Feb. 13 statement. “We are pleased with today’s phase 3 Align results, which add to the growing evidence of Vanrafia as a potential foundational therapy to slow kidney function decline.”Vanrafia gained its FDA accelerated approval in April 2025. As part of Novartis’ 2023 acquisition of Chinook Therapeutics, Vanrafia was Novartis’ second IgAN drug to cross the FDA finish line. The selective endothelin A receptor antagonist (ERA) does not come with the burden of an FDA-mandated REMS safety program, which sets it apart from Filspari.Besides Vanrafia, Novartis has Fabhalta, a complement inhibitor that showed statistically significant superiority compared with placebo in slowing IgAN progression measured by eGFR changes over two years. Novartis announced the positive final analysis from the phase 3 Applause-IgAN study in October and plans regulatory submissions this year. Originally approved by the FDA in December 2023 for the treatment of paroxysmal nocturnal hemoglobinuria, Fabhalta added an accelerated approval in IgAN in 2024 and then became the first FDA-approved therapy for C3 glomerulopathy in March 2025. The drug nearly tripled sales last year to $505 million, and Novartis has put its peak sales potential across multiple indications at above $3 billion.IgAN is a progressive autoimmune kidney disease that sees about 25 million new diagnoses each year worldwide, according to Novartis.To tackle the disease from a third angle, Novartis is testing its anti-APRIL antibody zigakibart in the phase 3 Beyond trial. The company recently amended the study’s protocol to focus on eGFR to potentially directly support a full approval. An interim eGFR readout is expected in the first half of 2027.

In ALIGN study, Vanrafia (atrasentan) showed positive difference in eGFR change from baseline vs. placebo at Week 136, 4 weeks after study treatment ended1 Results favored Vanrafia across multiple timepoints, measures of kidney function and in patients additionally receiving SGLT2 inhibitors1 Vanrafia received accelerated approval in U.S. and China for reduction of proteinuria in adults with IgAN in 2025; Novartis plans to submit for traditional approval in 20262 Basel, February 13, 2026 – Novartis today announced final results from the Phase III ALIGN study supporting a slowing decline in kidney function in adults with IgA nephropathy (IgAN) who were treated with Vanrafia® (atrasentan). Vanrafia showed a difference of 2.39 ml/min/1.73m2 in estimated glomerular filtration rate (eGFR) change from baseline vs. placebo (2-sided p = 0.057) at Week 136, 4 weeks after the end of study treatment1. Clinically meaningful results were observed with Vanrafia compared to placebo in eGFR change from baseline at the end of study treatment at Week 132, and in the prespecified exploratory group of patients additionally receiving sodium-glucose co-transporter-2 (SGLT2) inhibitors1. At the end of treatment at Week 132, the eGFR change from baseline compared to placebo was 2.59 ml/min/1.73 m2 (nominal 2- sided p = 0.039)1.“Progressive and complex diseases such as IgAN present an urgent need for medicines that can target the different drivers of the disease. Vanrafia can be seamlessly integrated into patients’ existing treatment plans, with a consistent safety profile,” said Ruchira Glaser, M.D., Global Head, Cardiovascular, Renal & Metabolic Development Unit, Novartis. “We are pleased with today’s Phase III ALIGN results, which add to the growing evidence of Vanrafia as a potential foundational therapy to slow kidney function decline.”ALIGN provides the longest follow-up period in pivotal Phase III studies for IgAN3. Safety was consistent with previous findings1. Alongside Vanrafia, Novartis continues to advance its multi-asset IgAN portfolio, which also includes Fabhalta® (iptacopan) and investigational compound zigakibart.About IgANIgAN is a progressive autoimmune kidney disease with approximately 25 per million people newly diagnosed worldwide each year4. IgAN is highly debilitating as it leads to glomerular inflammation (when the small filters in the kidneys are inflamed), proteinuria (excess protein in urine), and a gradual decline in eGFR5. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management5-7.Furthermore, people living with IgAN often face mental, social, and economic challenges5-8. Supportive care has not addressed the underlying causes of the disease and often fails to slow disease progression, reinforcing the need for more targeted therapies for IgAN4-9.About Vanrafia® (atrasentan) Vanrafia (atrasentan) is a potent and highly selective endothelin A (ETA) receptor antagonist, which is part of the endothelin system, a key system involved in the progression of IgAN10-13.Vanrafia is the first and only selective ETA receptor antagonist approved for primary IgAN, a once-daily, oral treatment and can be seamlessly added to, or used alongside, existing supportive care (e.g. renin-angiotensin system (RAS) inhibitor with or without SGLT2 inhibitor) without the need for titration2. Vanrafia does not require a Risk Evaluation and Mitigation Strategy (REMS) program. Because some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure, clinicians should obtain liver enzyme testing before initiating Vanrafia and during treatment when clinically indicated. Vanrafia may cause serious birth defects2.About ALIGNThe ALIGN study (NCT04573478) is a global, randomized, multicenter, double-blind, placebo-controlled Phase III clinical trial comparing the efficacy and safety of Vanrafia versus placebo in patients with IgAN at risk of progressive loss of kidney function1-3. In total, 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day despite optimized RAS inhibitor treatment were randomized to receive once-daily, oral Vanrafia (0.75 mg) or placebo for approximately 132 weeks1,11. Patients continue receiving a maximally tolerated and stable dose of a RAS inhibitor as supportive care1,11. An additional cohort of 64 patients receiving an SGLT2 inhibitor in addition to RAS inhibitor for at least 12 weeks was also enrolled1,11. The primary efficacy endpoint for the interim analysis (in 270 patients) was change in proteinuria, as measured by 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to 36 weeks1,3,11. The key secondary endpoint for the final analysis is the change from baseline to 136 weeks in kidney function as measured by eGFR. Other secondary efficacy endpoints as well as safety and tolerability are also assessed1-3.Novartis commitment to kidney diseases Building on a legacy of more than 40 years that began in transplant, Novartis is on a mission to empower breakthroughs and transform care in kidney health, starting with kidney conditions that have significant unmet need. Historically, these conditions have had considerably less funding and research, leading to a treatment landscape largely focused on reactive or end-stage disease management, often with significant physical, emotional, and financial burdens. Our portfolio targets the underlying causes of disease, with an aim to protect kidney health and delay or prevent dialysis and/or transplantation. Our goal is to help patients get back to living life on their terms - whether at work, in school, or with loved ones, and by partnering with patients, advocates, clinicians and policymakers, we aim to raise awareness, accelerate diagnosis, and get patients the right care, sooner.DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide.Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.References Novartis. Data on file. Novartis Pharmaceuticals Corporation. Novartis receives FDA accelerated approval for Vanrafia® (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN). Available at: https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-vanrafia-atrasentan-first-and-only-selective-endothelin-receptor-antagonist-proteinuria-reduction-primary-iga-nephropathy-igan. Accessed February 2026. ClinicalTrials.gov. NCT04573478. A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Atrasentan in Patients with IgA Nephropathy at Risk of Progressive Loss of Renal Function. Available at https://clinicaltrials.gov/study/NCT04573478. Accessed February 2026. Cheung C, Barratt J. The rapidly changing treatment landscape of IgA nephropathy. Semin Nephrol. 2025;44:151573. Kwon CS, Daniele P, Forsythe A et al. A systematic literature review of the epidemiology, health-related quality of life impact, and economic burden of immunoglobulin a nephropathy. J Health Econ Outcomes Res. 2021;8:36–45. Pitcher D, Braddon F, Hendry B et al. Long-term outcomes in IgAN. Clin J Am Soc Nephrol. 2023;18:727–8. Mohd R, Mohammad Kazmin NE, Abdul Cader R, et al. Long-term outcome of immunoglobulin A (IgA) nephropathy: a single center experience. PLoS One. 2021;16:e0249592. National Kidney Foundation. The voice of the patient (2020). Available at: https://igan.org/wp-content/uploads/2021/01/VOP_IgAN_12-7-20__FNL.pdf. Accessed February 2026. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100:S1–276. Barratt J, Kim SG, Inker LA et al. AFFINITY study: 1-year results of atrasentan in IgAN. J Am Soc Nephrol. 2024;35(Suppl):720. Abstract FR-P0855. Heerspink HJL, Jardine M, Kohan DE et al. Atrasentan in patients with IgAN. N Engl J Med. 2025;392:544–54. Heerspink HJL, Jardine M, Kohan DE et al. Study design and baseline characteristics of ALIGN, a randomized controlled study of atrasentan in patients with IgAN. Kidney Int Rep. 2024;10:217–26. Kohan DE, Barratt J, Heerspink HJL et al. Targeting the endothelin A receptor in IgAN. Kidney Int Rep. 2023;8:2198–210. # # # Novartis Media RelationsE-mail: media.relations@novartis.com Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com