Company: VERA
Filing Date: 2025-02-28
Form Type: 10-K
Source: 0000950170-25-029969
Chunk: 182

Company: Vera Therapeutics, Inc.
Filing Date: 2025-02-28
Form: 10-K
Item: Item 1
Chunk 182
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, after 36 weeks of treatment. Importantly, atacicept is the first agent in development to demonstrate Gd-IgA1 reductions, hematuria improvements, and UPCR reductions with eGFR stabilization at a rate of decline similar to the general population without kidney disease through 96 weeks, suggesting atacicept may offer a potential long-term, disease-modifying treatment for IgAN with a favorable safety profile.

These agents can be grouped mechanistically into the following categories: glucocorticoid receptor agonists, endothelin receptor antagonists (ERAs), complement inhibitors, B cell modulators, and a variety of other approaches that are earlier in development.

Glucocorticoid receptor agonists. Glucocorticoid receptor agonists are a well-known class of molecules that have broad anti-inflammatory effects, and well-established acute and chronic side effects. Though reduction in the risk of eGFR decline was shown in clinical trials, there is no consensus on whether glucocorticoids may improve renal survival. The glucocorticoid budesonide has been reformulated to concentrate steroid effects locally on the gut mucosa, theoretically suppressing the abnormal B cell activity and reducing systemic steroid toxicity. Reformulated budesonide is currently approved by the FDA and European Commission for reducing the loss of kidney function in adults with IgAN who are at risk for disease progression, though systemic steroid side effects have been observed in clinical trials.

ERAs. Aberrant endothelin signaling is implicated in structural podocyte changes and increased mesangial proliferation in chronic kidney diseases, including IgAN. ERAs block endothelin-induced cell proliferation and hence may reduce renal perfusion pressure and proteinuria. Since this mechanism of action works downstream of disease-related immune activities, it is not expected to reduce Gd-IgA1 or the resulting immune complexes that cause the disease. ERAs have previously been approved for the treatment of pulmonary arterial hypertension and erectile dysfunction and make use of a vasodilatory effect. One ERA that is currently approved by the FDA has a boxed warning for hepatotoxicity and embryo-fetal toxicity and a Risk Evaluation and Mitigation Strategies (REMS) assigned for liver toxicity, and another ERA is completing Phase 3 development. ERAs have been associated with edema, significant liver toxicity and increased risk of heart failure.

Complement inhibitors. Increased complement activation is commonly observed in patients with IgAN. It is hypothesized that immune-complex deposition in glomeruli may contribute to complement activation, though the exact mechanism