Everest Medicines Reports Positive Phase 1b/2a Trial Results for EVER001 in Treating Primary Membranous Nephropathy

Everest Medicines, a biopharmaceutical company centered on developing innovative treatments, has announced promising results from their ongoing Phase 1b/2a clinical trial investigating EVER001 for primary membranous nephropathy (pMN). EVER001, formerly known as XNW1011, is a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor thought to provide superior selectivity and potency compared to previous BTK inhibitors, while minimizing side effects.

The trial, underway in China, involves 31 patients with biopsy-confirmed pMN and positive anti-PLA2R autoantibodies. Participants were divided into two dosage cohorts, each undergoing a 36-week treatment period. The analysis of data collected up to September 13, 2024, revealed that in the low-dose cohort, 81.8% (9 out of 11) of patients attained overall clinical remission after 36 weeks, and 91% (10 out of 11) achieved immunological complete remission (ICR). The high-dose group showed 85.7% (6 out of 7) of patients attaining overall clinical remission by week 24, with all patients achieving ICR.

The treatment demonstrated substantial efficacy in reducing proteinuria and anti-PLA2R antibody levels. In the low-dose cohort, the geometric least squares mean 24-hour proteinuria dropped by 78.3% by week 36, while the high-dose cohort achieved a 73.8% reduction by week 24. Remarkably, EVER001 treatment led to greater than 90% reductions in anti-PLA2R antibody levels by weeks 24 and 12 in the low and high-dose cohorts respectively.

Importantly, the trial highlighted the favorable safety profile of EVER001. Patients did not report significant adverse events commonly linked to earlier-generation BTK inhibitors, such as bleeding, arrhythmia, severe infection, leukopenia, thrombocytopenia, or severe liver function impairment.

Rogers Yongqing Luo, CEO of Everest Medicines, expressed enthusiasm about the preliminary results, suggesting that they validate the potential of EVER001 as a next-generation BTK inhibitor for treating autoimmune renal diseases, including pMN. The company aims to further the global development of EVER001 to address urgent clinical needs.

Membranous nephropathy, a prevalent form of nephrotic syndrome among adults in China, affects approximately 2 million individuals in the nation, with significant populations also in the United States, Europe, and Japan. Currently, there are no approved medications specifically for pMN, and the primary treatment goals focus on enhancing remission rates, lowering relapse rates, and minimizing chronic toxicity from existing treatments. Despite current treatment protocols, over one-third of pMN patients progress to end-stage renal disease.

The Phase 1b/2a clinical trial received approval from the Center for Drug Evaluation of the National Medical Products Administration in September 2022. This trial aims to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of EVER001 in Chinese patients with proteinuria-related glomerular diseases. Prior Phase 1 studies in healthy subjects in China and Australia, conducted by SinoMab BioScience, showcased the high selectivity, optimal pharmacokinetics, robust target binding, and good safety profile of EVER001.

EVER001 is a covalent reversible BTK inhibitor in global development for renal diseases. BTK is crucial in B-cell receptor signaling, which influences the survival, activation, proliferation, and differentiation of B lymphocytes. Small molecule inhibitors targeting BTK have been effective in treating B-cell lymphomas and autoimmune diseases. Everest Medicines holds exclusive global rights to develop, manufacture, and commercialize EVER001 for renal diseases under a licensing agreement with Sinovent Pharmaceuticals and SinoMab BioScience.

Everest Medicines continues to drive forward the clinical development of EVER001, aiming to meet the critical unmet medical needs of patients with renal diseases.