Everest Medicines announced positive preliminary results from its ongoing Phase 1b/2a clinical trial of EVER001, a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor for treating primary membranous nephropathy (pMN). The results were presented at the 62nd Congress of the European Renal Association (ERA 2025), marking the first international presentation of data for this potential breakthrough therapy.
The trial enrolled 31 patients with biopsy-proven pMN who tested positive for anti-PLA2R autoantibodies across two dose cohorts in China. As of December 17, 2024, extended follow-up data showed 10 patients in the low-dose cohort completed 52 weeks of follow-up, while 10 patients in the high-dose cohort completed 24 weeks of treatment.
Significant Biomarker and Clinical Improvements
EVER001 demonstrated substantial reductions in disease-specific biomarkers. Anti-PLA2R autoantibody levels decreased by 62.1% in the low-dose cohort and 87.3% in the high-dose cohort at week 12, with both cohorts achieving approximately 93% reduction by week 24. Immunological complete remission was achieved by 76.9% of patients in the low-dose cohort and 81.8% in the high-dose cohort at week 24.
Proteinuria, a key clinical endpoint, showed marked improvement across both treatment groups. The low-dose cohort demonstrated a 78.0% reduction in 24-hour proteinuria by week 36, with this improvement sustained through week 52 and maintained for 16 weeks after treatment discontinuation. The high-dose cohort achieved a 70.1% reduction in proteinuria by week 24. Clinical remission rates reached 69.2% in the low-dose group at week 36 and 80.0% in the high-dose group at week 24.
Favorable Safety Profile
The treatment exhibited a favorable safety and tolerability profile, with most treatment-related adverse events classified as Grade 1-2. Notably, EVER001 did not produce clinically significant adverse events commonly associated with covalent irreversible BTK inhibitors, including bleeding, arrhythmia, severe infections, or severe liver function impairment. Patients in both cohorts maintained stable renal function throughout the treatment period.
Addressing Critical Unmet Medical Need
Primary membranous nephropathy represents a significant unmet medical need, with no approved drugs available globally for this indication. The condition affects approximately 2 million patients in China and nearly 220,000 patients in the United States, Europe, and Japan. pMN ranks as the second most common cause of primary glomerulonephritis and represents a common pathological type of nephrotic syndrome in adults, with increasing prevalence in China.
More than one-third of pMN patients progress to end-stage renal disease under current standards of care. Traditional immunosuppressive therapies carry high relapse risks following discontinuation and are associated with significant adverse effects.
Next-Generation BTK Inhibitor Technology
EVER001 distinguishes itself from earlier BTK inhibitors through its covalent reversible mechanism, offering improved selectivity while maintaining high potency. This design potentially avoids many side effects associated with earlier-generation BTK inhibitors. BTK serves as an essential component of B-cell receptor signaling pathways that regulate survival, activation, proliferation, and differentiation of B lymphocytes.
Professor Minghui Zhao, leading principal investigator and nephrologist at Peking University First Hospital, emphasized the drug's potential: "As a next-generation BTK inhibitor, EVER001 offers key advantages, including covalent reversibility, high selectivity, strong target-binding affinity, and reduced off-target toxicity. These attributes highlight its substantial potential in the treatment of pMN."
Broader Therapeutic Potential
Beyond pMN, EVER001 shows promise for treating other autoimmune renal diseases, including IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, and lupus nephritis, potentially offering treatment options for over 10 million patients worldwide.
Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines, stated: "As a potential best-in-class therapy, EVER001 holds promise to offer more treatment options for over 10 million patients worldwide affected by pMN, IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, and lupus nephritis."
The Phase 1b/2a clinical trial was approved by the Center for Drug Evaluation of the National Medical Products Administration in September 2022. Everest Medicines holds global rights to develop, produce, and commercialize EVER001 for renal diseases under an exclusive licensing agreement with Sinovent Pharmaceuticals and SinoMab BioScience.
