Everest Medicines announced positive results from its Phase 1b/2a clinical trial of EVER001, a next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of primary membranous nephropathy (pMN). The trial, conducted in China, demonstrated promising efficacy and safety data, positioning EVER001 as a potential breakthrough therapy for this challenging renal disease.
Clinical Remission Rates
The Phase 1b/2a trial enrolled 31 patients with biopsy-proven pMN who tested positive for anti-PLA2R autoantibodies. Patients were divided into low-dose and high-dose cohorts. According to data collected as of September 13, 2024:
- In the low-dose cohort, 9 out of 11 patients (81.8%) achieved overall clinical remission after 36 weeks of treatment.
- In the high-dose cohort, 6 out of 7 patients (85.7%) achieved overall clinical remission by week 24.
Immunological Complete Remission
In addition to clinical remission, the trial assessed immunological complete remission (ICR). The results showed:
- 10 out of 11 patients (91%) in the low-dose cohort achieved ICR.
- All patients in the high-dose cohort achieved ICR by week 24.
Reduction in Proteinuria and Anti-PLA2R Antibody Levels
The trial also evaluated the impact of EVER001 on proteinuria and anti-PLA2R antibody levels. The geometric least squares mean 24-hour proteinuria decreased significantly:
- 78.3% reduction at week 36 compared to baseline in the low-dose cohort.
- 73.8% reduction at week 24 compared to baseline in the high-dose cohort.
Furthermore, 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.
Safety and Tolerability
EVER001 was generally safe and well-tolerated. Notably, 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.
Mechanism of Action and Potential Advantages
EVER001 is a covalent reversible BTK inhibitor designed with potentially best-in-class characteristics for treating autoimmune renal diseases. Compared to covalent irreversible BTK inhibitors, EVER001 offers improved selectivity while maintaining high potency, potentially avoiding many side effects associated with earlier-generation BTK inhibitors.
Market Opportunity and Unmet Need
Primary membranous nephropathy is a common pathological type of nephrotic syndrome in adults, with increasing prevalence, especially in China, which has an estimated 2 million patients. There are approximately 80,000 to 100,000 patients in the United States and 80,000 in Europe. Currently, there are no approved drugs for pMN worldwide, highlighting a significant unmet medical need. Current treatments aim to improve remission rates, reduce relapse rates, and minimize chronic toxicity, but over one-third of pMN patients still progress to end-stage renal disease under current standards of care.
Everest Medicines' Strategy
"We are excited to see the encouraging results in this preliminary analysis of our Phase 1b/2a clinical proof-of-concept trial of EVER001," said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines. "This demonstrates the potential of EVER001 as a next-generation BTK inhibitor for the treatment of various autoimmune renal diseases, including pMN... Moving forward, we will continue to drive the global clinical development of EVER001, to meet patients' urgent clinical needs."
