An experimental Roche drug reduced levels of urine proteins indicative of disease in a Phase 3 clinical trial, results that could position the therapy to join an increasingly competitive market of treatments for a rare autoimmune disorder affecting the kidneys.
The chronic disease is called immunoglobulin A nephropathy, or IgAN. Detailed data from the trial were not disclosed but Roche said Wednesday that a prespecified interim analysis shows the study drug, sefaxersen, achieved statistically significant and clinically meaningful improvement in lowering levels of urine proteins. The company added that the data will be presented at an upcoming medical conference and shared with regulatory authorities.
In IgAN, the body produces autoantibodies that accumulate in the kidneys, leading to inflammation and organ damage. This disease can progress to end-stage renal failure. Sefaxersen is an antisense oligonucleotide (ASO) designed to target messenger RNA for factor B, reducing blood levels of this complement system protein. Reducing those levels is intended to lead to improvement in kidney function. Sefaxersen was initially developed by ASO specialist Ionis Pharmaceuticals. In 2018, Roche began a partnership on the drug. Roche acquired full rights to the IgAN drug candidate in 2022, then proceeded to advance it to Phase 3 testing.
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IgAN patients already have access to a factor B inhibitor: Novartis’s iptacopan, which was approved in this indication in 2024. Marketed as Fabhalta, the drug is an oral small molecule taken twice daily. Right now, it’s the only complement system inhibitor available for IgAN. But the product’s label carries a black box warning for the increased risk of serious and life-threatening infections, which is consistent with other complement inhibitors.
Though detailed data are not yet available for comparison, Roche’s drug still has the potential for dosing and safety advantages. It’s true that many patients prefer pills to injections, but it can be difficult to maintain twice-daily oral dosing for a chronic disease therapy. Sefaxersen was developed for monthly injections, which Roche said patients could administer at home. The need for less frequent dosing may be more convenient for some patients. Detailed safety data were not reported, but Roche said safety and tolerability of the drug is consistent with previously reported data. In a research note, William Blair analysts said mitigation of the bacterial infection risk would be differentiating for the Roche drug, and perhaps necessary for a longer-acting drug in this class.
The longer-acting IgAN medicines currently available are biologic drugs. Last fall, the FDA approved Otsuka’s Voyxact, an antibody designed to block APRIL, a protein that stimulates production of autoantibodies. This past July, Vera Therapeutics received an FDA nod for Trutakna, a fusion protein designed to block APRIL and BAFF. Both drugs are administered as weekly injections. Vertex Pharmaceuticals is vying to bring patients an alternative that’s dosed monthly. This APRIL- and BAFF-blocking fusion protein, named povetacicept, is currently under FDA review with regulatory decision expected by the end of November.
Reducing levels of urine proteins was the benchmark that supported the accelerated FDA approvals of the currently available IgAN drugs. Likewise, sefaxersen’s interim results showing reduction in urine proteins could be sufficient to support an application seeking accelerated FDA approval. The Phase 3 test of this Roche drug remains blinded and is continuing to assess the therapy’s effect on kidney function over the course of two years. Those results could support a traditional approval. In July, Novartis’s Fabhalta converted its regulatory status to a full approval based on clinical data showing a slowing in the decline of kidney function. Roche’s drug could follow the same path.
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“These interim Phase 3 results show the clinical potential of sefaxersen to modify a key surrogate endpoint of kidney function in people with IgA nephropathy,’’ Levi Garraway, Roche’s chief medical officer and head of global product development said in a prepared statement. “Sefaxersen may therefore offer a new treatment option to help slow disease progression and potentially reduce the long-term need for dialysis or kidney transplantation.”
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