Iptacopan

AstraZeneca’s (LSE/STO/NYSE: AZN) Alexion unit reported that ravulizumab (Ultomiris) met the proteinuria primary endpoint in a prespecified interim analysis of the Phase III I CAN trial in adults with immunoglobulin A nephropathy, adding a potential new indication to a drug already approved across four complement-mediated diseases. The I CAN trial (ALXN1210-IgAN-320) is a global, randomized, double-blind, placebo-controlled study enrolling approximately 510 adults with IgAN who are at risk of disease progression, randomized 1:1 to ravulizumab or placebo for 106 weeks across 28 countries. At the week-34 interim analysis, ravulizumab produced a statistically significant reduction in proteinuria measured by 24-hour urine protein-to-creatinine ratio (UPCR) compared with placebo. The company reported that the reduction was detectable as early as week 10. No specific effect sizes, p-values, or confidence intervals were disclosed in the announcement; full data are expected at a forthcoming medical meeting. The second primary endpoint — change from baseline in estimated glomerular filtration rate at week 106 — remains pending at the final analysis. Safety was described as consistent with the established Ultomiris profile, with no new concerns identified. The decision to pursue accelerated approval in key markets on the basis of proteinuria reduction reflects a regulatory strategy that has precedent in IgAN. The FDA granted accelerated approval to sparsentan (Filspari, Travere Therapeutics) in 2023 on the basis of proteinuria reduction, with confirmatory eGFR data required. Iptacopan (Fabhalta, Novartis), a factor B inhibitor targeting the alternative complement pathway, received FDA approval for IgAN in 2024, also using proteinuria as the primary basis. The I CAN trial results position ravulizumab as a terminal complement inhibitor entering a space where upstream and midstream complement blockade already have regulatory footholds. The mechanistic distinction matters for how the data will be interpreted. IgAN pathogenesis involves aberrant IgA1 glycosylation leading to immune complex deposition in the glomerular mesangium, which activates the complement cascade. Iptacopan acts at factor B in the alternative pathway, upstream of C5. Ravulizumab blocks C5 cleavage directly, preventing generation of both the anaphylatoxin C5a and the membrane attack complex C5b-9. Whether terminal inhibition at C5 offers a different or additive clinical profile compared with upstream blockade is a question the field has not yet resolved, and cross-trial comparisons are limited by differences in patient populations, background therapy, and endpoint definitions across studies. Ravulizumab is an engineered variant of eculizumab with modifications that extend its half-life, allowing every-eight-week intravenous dosing in adults rather than the fortnightly schedule required for eculizumab. That pharmacokinetic profile has been central to its commercial positioning across its approved indications — paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. In IgAN, the dosing interval could be relevant for patient adherence, though the intravenous route itself remains a practical consideration relative to oral agents such as iptacopan or sparsentan. The IgAN treatment landscape has shifted substantially since 2021, when the field had few options beyond renin-angiotensin-aldosterone system blockade and corticosteroids. Budesonide (Tarpeyo/Kinpeygo, Calliditas Therapeutics) received accelerated FDA approval in 2021 targeting mucosal IgA production. Sparsentan, a dual endothelin and angiotensin receptor antagonist, followed in 2023. Iptacopan, the first complement-targeted oral therapy for IgAN, added another mechanistic layer. The entry of a terminal C5 inhibitor with an established safety record across multiple approved indications introduces a drug with a known tolerability profile into this evolving treatment algorithm, though its precise positioning — monotherapy, add-on, or use in specific complement-driven subpopulations — will depend on the full week-106 dataset and regulatory review. The absence of numerical efficacy data in the current disclosure limits clinical interpretation. Proteinuria reduction is an accepted surrogate in IgAN, but the magnitude of that reduction, and whether it is sustained, carries weight for both regulatory and clinical decision-making. The FDA’s accelerated approval pathway for IgAN has explicitly tied post-marketing requirements to longer-term kidney function outcomes, meaning the eGFR readout at week 106 will be the more consequential dataset for understanding whether ravulizumab modifies disease trajectory rather than simply attenuating a biomarker. AstraZeneca said it plans to file for accelerated approval in key markets while the trial continues toward its final analysis, with full results to be presented at an unspecified medical meeting. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Novartis has been steadily dialing back its U.S. workforce in recent years. Novartis is making further workforce reductions at its U.S. headquarters in New Jersey, planning to eliminate 114 positions as the drugmaker rejigs its sales team for rare-disease medicines.The Swiss pharma telegraphed the layoffs in a recent Worker Adjustment and Retraining Notification (WARN) filing (PDF) to the state, with the cuts slated to take effect from late June to November. “[O]ur US Customer Engagement organization has been evaluating opportunities to evolve our field sales team structures to better support the unique needs of patients and customers in the rare and ultra-rare disease spaces—where Novartis has a strong footprint and focus with in-market products and upcoming pivotal launches,” a Novartis spokesperson told Fierce Pharma. “To that end, we are making some organizational changes that result in some roles being eliminated, modified, and created.”  The adjustment marks the latest in a series of layoffs at Novartis, which can be traced all the way back to a major reorganization launched in 2022. Novartis offers several drugs in the rare disease space. These include chronic myeloid leukemia therapy Tasigna and Promacta for treating low blood platelet counts in certain patients, including those with the rare blood disorders chronic immune thrombocytopenia (ITP) and aplastic anemia. The two meds, together with the megablockbuster heart failure treatment Entresto, form the largest single-year patent cliff in Novartis’ history, presenting a notable challenge for the company in 2026.Novartis is also managing a few new rare disease launches in the autoimmune field, including Rhapsido for chronic spontaneous urticaria (CSU). It’s additionally rolling out two rare kidney disease therapies, Vanrafia and Fabhalta, in IgA nephropathy. Further, the dual-mechanism, B-cell-depleting antibody ianalumab is nearing the market after a pair of phase 3 wins in Sjögren’s, while a first-line ITP pivotal readout is expected this year. “Novartis continually assesses opportunities to adapt in alignment with our evolving pipeline, patient, and customer needs. As such, we direct our efforts and talent toward areas where we can create the greatest potential impact for patients and customers,” the company spokesperson said.  Novartis has made multiple cuts tied to its New Jersey HQ in the past few years. In September, it laid out a plan to lay off 58 employees in its U.S. medical affairs organization, following another overhaul of its cardiovascular commercial structure that affected 427 employees.The Swiss pharma has been steadily dialing back its U.S. workforce in recent years. Coinciding with the separation of the biosimilars and generics unit Sandoz, Novartis’ U.S. headcount, measured by full-time equivalents, dropped by nearly 12% year over year to 12,846 in 2023. As of the end of last year, the company had 12,556 full-time employees stateside. Globally, Novartis is only one of two large pharma companies that have consistently slimmed down every year between 2021 and 2025, according to a recent Fierce Pharma analysis.  While its U.S. commercial team and general and administrative functions have become smaller, Novartis beefed up its manufacturing headcount by 25% last year to 1,479 people. Following an industry-wide trend to avoid potential pharmaceutical tariffs by the Trump administration, Novartis last year unveiled a $23 billion investment to grow its U.S. footprint in production and R&D.