Vera Kidney Drug Wins Approval, Enhertu UK Deal Reached

IgA nephropathy, a chronic autoimmune kidney disease, affects millions globally, often leading to progressive renal decline and eventual kidney failure. Current management strategies, primarily focused on blood pressure control and proteinuria reduction with renin-angiotensin system inhibitors, frequently fall short in halting disease progression. This unmet need has driven the development of targeted immunomodulatory therapies.

Vera Therapeutics' atacicept, a fusion protein that inhibits B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), has now received FDA approval for adult patients with IgAN at risk of rapid progression. The approval follows data from the Phase 2b ORIGIN trial, which evaluated atacicept's efficacy and safety in reducing proteinuria, a key surrogate marker for kidney disease progression. The trial enrolled 116 adult patients with biopsy-proven IgAN and persistent proteinuria despite optimised standard of care, randomising them to either atacicept 150 mg once weekly or placebo for 36 weeks.

What the trial actually measured

The ORIGIN trial's primary endpoint was the change in proteinuria, measured by urine protein-to-creatinine ratio (UPCR), from baseline to week 36. Patients receiving atacicept demonstrated a significant reduction in proteinuria, with a mean change of -33% compared to placebo (p=0.0001). This reduction was consistent across various subgroups, including those with higher baseline proteinuria and different eGFR categories. The magnitude of proteinuria reduction is clinically meaningful, given its strong correlation with long-term renal outcomes in IgAN.

Secondary endpoints reinforced the primary findings. Atacicept treatment led to a sustained reduction in serum galactose-deficient IgA1 (Gd-IgA1) levels, a biomarker strongly implicated in IgAN pathogenesis, by 45% (p<0.0001). This mechanistic effect on Gd-IgA1, which drives immune complex formation and subsequent renal damage, supports the drug's targeted approach. The drug also showed a favourable safety profile, with the most common adverse events being mild to moderate infections, consistent with its immunomodulatory mechanism. No new safety signals emerged during the trial, and discontinuations due to adverse events were low.

But the ORIGIN trial was a Phase 2b study, meaning its primary objective was to establish proof-of-concept and determine an optimal dose, not to definitively demonstrate long-term kidney preservation. The relatively small sample size (N=116) and the 36-week duration mean that direct evidence on hard renal outcomes, such as eGFR decline or progression to end-stage kidney disease, is still pending. These critical long-term data will be evaluated in the ongoing Phase 3 ORIGIN-3 trial, which is designed to assess the impact of atacicept on eGFR slope over a longer period. The current approval relies on proteinuria reduction as a surrogate endpoint, a common practice in nephrology trials but one that always warrants caution regarding direct clinical benefit.

Still, the approval provides a much-needed option for patients with IgAN, a disease for which treatment options have historically been limited. The drug's mechanism, targeting both BAFF and APRIL, offers a distinct approach compared to other investigational agents that focus solely on one pathway. This dual inhibition aims to more comprehensively reduce the production of pathogenic autoantibodies and immune complexes. The clinical community has long awaited therapies that move beyond symptomatic management to address the underlying immunological drivers of IgAN. Atacicept represents a step in that direction, offering a targeted intervention for a complex autoimmune condition.

Meanwhile, in the United Kingdom, a new pricing and access agreement has been reached for trastuzumab deruxtecan (Enhertu) for patients with HER2-low metastatic breast cancer. This agreement, facilitated by NHS England and Daiichi Sankyo, will expand access to the antibody-drug conjugate for a patient population previously underserved by HER2-targeted therapies. Enhertu is already established for HER2-positive metastatic breast cancer, but its efficacy in HER2-low disease, defined by immunohistochemistry (IHC) scores of 1+ or 2+ with a negative in situ hybridisation (ISH) test, represents a significant expansion of its utility. The drug demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS) in the DESTINY-Breast04 trial, which enrolled patients with HER2-low metastatic breast cancer who had received prior chemotherapy. The median PFS was 9.9 months for Enhertu versus 5.1 months for chemotherapy (HR 0.50; 95% CI, 0.40-0.63; P<.001), and median OS was 23.4 months versus 16.8 months (HR 0.64; 95% CI, 0.49-0.84; P=.001). This agreement means that a substantial number of patients in the UK will now have access to a therapy that has shown clear survival benefits in a difficult-to-treat subset of breast cancer. The economic considerations for such high-cost therapies are always a hurdle, but this deal underscores the commitment to making effective treatments available when the clinical evidence is compelling.