{"id":6362,"date":"2026-03-31T22:26:02","date_gmt":"2026-04-01T04:26:02","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=6362"},"modified":"2026-04-02T11:41:25","modified_gmt":"2026-04-02T17:41:25","slug":"igan-therapeutics-the-race-is-on","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2026\/03\/31\/6362\/igan-therapeutics-the-race-is-on\/","title":{"rendered":"IgAN Therapeutics – The Race is On"},"content":{"rendered":"
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Is there a new trend in the journal world: \u00a0publication of interim analysis (IA) results?<\/p>\n\n\n\n

The NEJM recently published two articles back to back, both highlighting 9 month ‘interim’ data from Phase 3 pivotal trials in IgAN. The primary efficacy endpoint used in either study was UPCR at 9 months, a de-facto surrogate for eGFR stabilization [1]<\/a>,[2]<\/a>. We are talking about sibeprenlimab and atacicept, of course, an APRIL and BAFF\/APRIL inhibitor, respectively.<\/p>\n\n\n\n

Such interim demonstration of efficacy was acceptable to Regulators in the past as they gave conditional approval to iptacopan \/ Fabhalta based on 9-mo UPCR data; a recent press release claims that iptacopan also had positive effects on eGFR after 2 yrs of treatment [3]<\/a>. This was the path also taken by sibeprenlimab \/ Voyxact which obtained conditional approval in Nov 2025; for this drug, long-term 2-yr GFR data are still pending. Going back further, the same pattern is seen with the approvals for budesonide \/ Tarpeyo and sparsentan \/ Filpari, in both cases UPCR was the trigger for submission and conditional approval.<\/p>\n\n\n\n

FDA always reserves the option to revoke an approval if the eGFR data do not show a benefit over placebo. This is reasonable: why would we expose patients to drugs that just lower proteinuria but otherwise have no impact on kidney function. For regulators, UPCR is just an ‘interim’ step, albeit an important one. For them, the primary endpoint remains eGFR even if sponsor protocols list UPCR as primary efficacy endpoints.<\/p>\n\n\n\n

Does this twisted nomenclature make sense? We usually associate an IA with decision-making before enrollment is complete. The question usually asked at the time of an IA: is there a need for sample size adjustment? Should a trial be stopped for futility? Here, however, we use the term IA like an interim endpoint for a co-primary result. The terms ‘interim’ and ‘primary’ take on a slightly different meaning from the traditional way we use those terms.<\/p>\n\n\n\n

What is the chance that a positive early UPCR signal may be followed by a negative late GFR read-out? We believe this risk is small but not negligible. Consider the following:<\/p>\n\n\n\n