Episode transcript · Evidence date: October 2026.
On October 21, 2026, AstraZeneca announced FDA accelerated approval of Ultomiris, or ravulizumab, to reduce urine protein in adults with primary IgA nephropathy at risk of progression.
In the phase 3 I CAN trial, it reduced urine protein by 43.4% versus placebo at 34 weeks.
But it has not yet been shown to slow kidney function loss.
Why approve it before that benefit is confirmed?
This is Before the Conclusion.
We start with medicine and science, take a fresh look at the evidence, and explore the reasoning and trade-offs behind research and decisions. We also look for ways to think through complex questions.
We look beyond the conclusions to the questions that remain unanswered, and how they may affect our lives.
First, what happens in IgA nephropathy?
IgA is a type of antibody. In this disease, immune complexes containing IgA collect in the kidneys. They trigger inflammation and damage the glomeruli, the tiny structures that filter blood.
When their filtration barriers are damaged, proteins that should stay in the blood can leak into the urine. This is called proteinuria.
IgA nephropathy can affect young people. Some remain stable for years. Others gradually lose kidney function and need dialysis or a transplant.
Less protein in the urine is welcome. But patients may care more about another question:
10 years from now, will my kidneys still work?
Kidney disease often progresses slowly. Waiting for enough patients to develop kidney failure could mean years of research while some continue losing kidney function.
Researchers need earlier signals of possible long-term benefit. Urine protein is one of them.
Its value goes beyond ease of measurement.
Long-term studies link higher urine protein and longer periods of elevation to kidney function loss. Across controlled trials, treatment-related reductions are also associated with better long-term kidney outcomes.
This supports using urine protein reduction as a surrogate endpoint reasonably likely to predict clinical benefit.
A surrogate endpoint is a measurement used to predict a clinical benefit. Here, researchers measure a drop in urine protein to help predict whether kidneys will keep working longer.
The key word is “predict.” Evidence supports the prediction. Uncertainty remains.
A marker may track disease progression. But changing it does not guarantee a drug will improve patients' future outcomes.
Did the drug reduce urine protein? And did kidney function decline more slowly?
The questions are related but need different evidence.
That is where accelerated approval comes in.
For serious diseases with unmet medical needs, the FDA can grant accelerated approval on that basis. Companies must then verify the expected benefit in further studies.
If confirmed, accelerated approval can become traditional, or full, approval. If not, the FDA can withdraw approval for that use.
Patients gain earlier access while long-term questions remain.
Ultomiris blocks C5, a protein in the complement system. Abnormal complement activation contributes to kidney inflammation and damage in IgA nephropathy.
I CAN is continuing follow-up. It will assess changes in estimated glomerular filtration rate, or eGFR, at 106 weeks. These results are intended to support traditional approval.
eGFR estimates how well the kidneys filter blood. Tracking it helps researchers assess whether kidney function declines more slowly than with placebo.
C5 also helps fight infection. Ultomiris carries a boxed warning for serious meningococcal infections. Treatment requires appropriate vaccination and infection risk management.
Expected benefits must be weighed against these risks.
On October 22, California-based Vera Therapeutics reported phase 3 results for atacicept in IgA nephropathy.
According to the company, ORIGIN 3's final efficacy analysis found positive results for urine protein, eGFR change, its annual rate of decline, and a composite endpoint tracking kidney disease progression.
Atacicept already has accelerated approval to reduce urine protein. Vera plans to seek full approval through a supplemental application in Q4 2026.
Longer follow-up adds evidence about kidney function to the earlier urine protein result.
These trials did not compare the drugs directly. Patients, designs, and follow-up may differ. Their numbers cannot establish which drug is better.
Company announcements also do not mean FDA review is complete.
Approval is one point in a longer story.
Before accelerated approval, regulators weigh whether current evidence justifies earlier access. Afterward, they must check whether the predicted benefit occurs.
Wait too long and patients may lose a chance to benefit. Earlier access means accepting treatment risks and burdens before long-term effects are clear.
The pathway's value depends on completed follow-up studies, public results, and regulatory decisions that respond to new evidence.
When reading medical news, ask:
What did the study measure? A signal of future benefit, or an outcome closer to patients' long-term needs?
How large was the improvement? How long did it last? What risks did treatment carry?
That makes “the trial succeeded” more specific.
So, if urine protein falls, are the kidneys protected?
In IgA nephropathy, lower urine protein is a meaningful positive signal supported by research.
For each drug, we still need to ask whether kidney function declines more slowly. How long does the benefit last? Is it worth the risk?
Patients need treatment options today. They also need continued follow-up to see how much of today's promise is fulfilled.
This is Before the Conclusion.
See you next time.