Everest Medicines, a biopharmaceutical company focused on the discovery, clinical development, manufacturing and commercialization of innovative therapeutics, has announced positive results in the ongoing Phase 1b/2a clinical trial for the treatment of primary membranous nephropathy (pMN) with EVER001 (previously known as XNW1011), a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor.
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In an analysis of the data available as of September 13th, 2024, results from the Phase 1b/2a clinical trial showed that for patients in the low-dose cohort who have completed 36 weeks of treatment, 9 out of 11 (81.8%) achieved overall clinical remission1 and 10 out of 11 (91%) achieved immunological complete remission (ICR)2. In the high dose cohort, 6 out of 7 (85.7%) patients achieved overall clinical remission and all patients achieved ICR by week 24.
EVER001 is a covalent reversible BTK inhibitor with potentially best-in-class characteristics for the treatment of autoimmune renal diseases. Compared to covalent irreversible BTK inhibitors, EVER001 offers improved selectivity while maintaining high potency, thereby potentially avoiding many of the side effects associated with earlier-generation BTK inhibitors. Everest Medicines holds global rights to EVER001 for the treatment of renal diseases.
The Phase 1b/2a clinical trial of EVER001 for the treatment of pMN is an ongoing trial conducted in China. A total of 31 patients with biopsy-proven pMN who tested positive for anti-PLA2R autoantibodies were enrolled into two cohorts. The total treatment duration was 36 weeks. Based on the patient data collected by September 13th, 2024, in the low-dose cohort, the geometric least squares mean 24-hour proteinuria decreased by 78.3% at week 36 compared to baseline, while the high-dose cohort achieved a 73.8% reduction by week 24. EVER001 treatment induced greater than 90% reductions in anti-PLA2R antibody as early as week 24 in the low-dose cohort and week 12 in the high-dose cohort. EVER001 was generally safe and well tolerated. No clinically significant adverse events typically associated with earlier-generation BTK inhibitors, such as bleeding, arrhythmia, severe infection, leukopenia, thrombocytopenia, or severe liver function impairment, were reported.
"We are excited to see the encouraging results in this preliminary analysis of our Phase 1b/2a clinical proof-of-concept trial of EVER001. This demonstrates the potential of EVER001 as a next-generation BTK inhibitor for the treatment of various autoimmune renal diseases, including pMN. "Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines, said："This data release marks the first time Everest Medicines has disclosed results from its global pipeline. We look forward to completing this trial and sharing detailed data in future conferences and publications. Moving forward, we will continue to drive the global clinical development of EVER001, to meet patients' urgent clinical needs.”
Membranous nephropathy is a common pathological type of nephrotic syndrome in adults, and its prevalence in China has been increasing, ranking second only to IgA nephropathy3. There are about 2 million patients with pMN in China, with an estimated 80,000 to 100,000 patients in the United States, 80,000 in Europe, and 40,000 in Japan. There are no approved drugs for this indication worldwide. The current treatment goal is to improve remission rates, reduce high relapse rates, and minimize the risk of chronic toxicity caused by currently available treatments. More than one-third of pMN patients still progress to end-stage renal disease under current standards of care.
This Phase 1b/2a clinical trial was approved by the Center for Drug Evaluation of the National Medical Products Administration in September 2022 to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of EVER001 in Chinese patients with glomerular diseases characterized by proteinuria. The previously published results of a Phase 1 study conducted in healthy Chinese and Australian subjects conducted by SinoMab BioScience indicate that EVER001 has high selectivity, excellent pharmacokinetic properties, a good safety profile, and strong target binding.