Data Considerations of Novel Immunotherapies for IgAN

Chee Kay Cheung, MBChB, MRCP, PhD: We’ve seen from the phase 2 data from ENVISION––which studied sibeprenlimab, an anti-APRIL agent––and also from the interim results from the ORIGIN trial, which studies atacicept, that these agents are looking promising in reducing the galactose deficient IgA1 [immunoglobulin A1], the pathogenic form of IgA, and also reducing IgA levels more generally, but they have less of an effect on reducing IgG levels. So these do seem to have a specific effect on targeting IgA production. And we know that IgG levels are important in terms of infection risk because of the known risk, known association between low IgG levels and increased infection that we’ve seen in other conditions; for example, in patients treated with rituximab in ANCA [antineutrophil cytoplasmic antibody]-associated vasculitis. So [those] data [are] reassuring. The best thing seems to be a class-specific effect of these drugs. We’ve also seen some reassuring vaccination data from the sibeprenlimab trials and ENVISION. There was…a COVID[-19] vaccine substudy, which showed that patients treated with sibeprenlimab were able to mount an adequate COVID[-19] vaccine response, which was comparable to [that of] patients not treated with sibeprenlimab, and also that rates of antibody against COVID[-19] declined at a similar rate [to that of] non-sibeprenlimab treated patients. We can infer some data from studies looking at belimumab, which is an anti-BLyS agent that’s being used for treatment of lupus, again showing that vaccine responses are maintained after belimumab is used for treatment. And these maintained vaccine responses really differ markedly compared [with those of] patients who are treated with rituximab––well, we know that vaccine responses are very poor––so I think that provides some reassurance. But we have to be vigilant…for longer-term effects as well of using these agents. And I think that’s why data from longer-term studies, from open-label extension studies, will be crucial to monitor.

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