VIDEO: 'Tectonic shifts' occurring in IgA nephropathy treatment landscape

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Well, I think I wouldn't be exaggerating when I say that we are experiencing some tectonic shifts in the landscape and the development of IgA nephropathy. Based on the basic and early stage clinical science, we now better understand the pathophysiology of IgA nephropathy. Let me provide you with few examples. Decades of basic science have led to our understanding of the vital role the local endothelin system plays in glomerular filtration and the pathophysiology of kidney disease. We have uncovered the role of gastrointestinal MALT, mucosal-associated lymphoid tissue as a site of origin for the pathogenesis of IgA nephropathy.

We have recognized the critical transition phase in B cell maturation that ultimately leads to the production of galactose deficient IgA. And we have recognized the central role the complement system plays within the glomerulus and the development and progression of IgA nephropathy. More recently, we gained more in depth insight into the longer-term outcomes of patients with IgA nephropathy based on epidemiological study using data from the UK National Registry of Rare Kidney, led by Jonathan Barratt and colleagues. And another retrospective study done by John Sims and colleagues, which examined the characteristics and outcomes of patients with IgA nephropathy at the Kaiser Permanente.

They have learned from these outcome studies, has been very sobering. Over a median follow-up period of around six years, 50% of patients diagnosed with IgA nephropathy either reached kidney failure or died. The gravity and mortality of these diagnosis are comparable and in some instances worse than that of a cancer diagnosis such as breast cancer, prostate cancer, or colon cancer. Therefore, our quest for safe and effective therapies is a matter of urgency. So it is inspiring that many of these recent understandings have translated directly into clinical care. We went from zero drugs approved in 2020 to now two drugs approved and available to patients, with many more in pipeline. These new therapies all act through some of the different mechanisms the scientists working in this field have uncovered. In early stage phase studies, they have been shown to decrease proteinuria.

And in phase three trials, two have been shown to protect kidney function and slow the progression of kidney disease. First came Tarpeyo (budesonide, Calliditas Therapeutics), which is targeted release budesonide, which received accelerated approval in December '21, and full approval by the FDA in December '23. It targets the gastrointestinal MALT, and leads to a reduction in proteinuria and the relative preservation of kidney function compared to placebo. Then came Filspari (sparsentan, Travere Therapeutics), a dual endothelial angiotensin receptor blocker, which received accelerated approval from the FDA in February, 2023. Filspari showed a reduction in proteinuria and the slowing of kidney function decline. So we have come a long way and are at a point where we can see sunlight at the end of the dark IgA nephropathy tunnel. But we also have miles to go to reach the other side and hopefully translate the tremendous opportunities ahead of us into day-to-day patient care for all patients with IgA nephropathy.