Everest Medicines, a biopharmaceutical company committed to pioneering the discovery, development, production, and commercialization of novel therapies, has shared promising outcomes from their ongoing phase 1b/2a trial evaluating EVER001 for primary membranous nephropathy (pMN). A cutting-edge covalent reversible Bruton’s tyrosine kinase (BTK) inhibitor, EVER001 (formerly known as XNW1011), illustrated positive results in the trial as of September 13, 2024. In patients who completed 36 weeks in the low-dose cohort, 81.8% (9 out of 11) achieved complete clinical remission, and 91% (10 out of 11) reached immunological complete remission (ICR). The high dose group showed 85.7% (6 out of 7) achieving clinical remission, with all participants reaching complete ICR by the 24th week.
EVER001 is designed to be a potentially superior BTK inhibitor for autoimmune renal conditions. Offering enhanced selectivity compared to its covalent irreversible predecessors, it maintains potent efficacy while potentially reducing side effects linked to older BTK inhibitors. Everest Medicines retains worldwide rights to develop EVER001 for renal disorder treatments.
Conducted in China, the phase 1b/2a study involves 31 biopsy-confirmed pMN patients positive for anti-PLA2R autoantibodies, divided into two dose groups for up to 36 weeks of treatment. As per the data until September 13, 2024, the low-dose cohort saw a substantial 78.3% reduction in geometric least squares mean 24-hour proteinuria at week 36 compared to baseline, whereas a 73.8% drop was noted in the high-dose group by week 24. Anti-PLA2R antibody levels dropped over 90% as early as week 24 for low doses and week 12 for higher doses. EVER001’s safety and tolerability profile was commendable, with no reports of major side effects such as bleeding, arrhythmias, infections, leukopenia, thrombocytopenia, or significant liver dysfunction often linked to earlier BTK inhibitors.
“The promising data from our phase 1b/2a proof-of-concept trial underscores EVER001’s potential as a promising next-gen BTK inhibitor for treating various autoimmune renal conditions, including pMN,” expressed Everest Medicines’ CEO, Rogers Yongqing Luo. He continued, “This marks the inaugural data sharing from Everest Medicines’ global research efforts. We are eager to finalize this trial and present comprehensive findings at future forums and publications as we advance EVER001’s global clinical development to address unmet clinical needs.”
Membranous nephropathy is among the prevalent nephrotic syndromes in adults, increasingly diagnosed in China, second only to IgA nephropathy. With approximately 2 million pMN patients in China, and estimated incidences of 80,000 to 100,000 in the U.S., 80,000 in Europe, and 40,000 in Japan, no approved medications exist globally for this indication. Treatment aims to enhance remission rates and lower relapse rates, while minimizing toxicity risks associated with current therapies. Over a third of pMN sufferers progress to end-stage renal disease despite current treatment standards.
The phase 1b/2a trial received approval in September 2022 from China’s National Medical Products Administration Center for Drug Evaluation, focusing on EVER001’s safety, efficacy, pharmacokinetic, and pharmacodynamic profiles in Chinese patients with proteinuria-driven glomerular diseases. Former findings from a phase 1 trial performed with healthy subjects in China and Australia by SinoMab BioScience affirm EVER001’s high selectivity, strong pharmacokinetic properties, sound safety profile, and robust target binding abilities.
EVER001, originally known as XNW1011, is a revolutionary covalent reversible BTK inhibitor worldwide under development for renal disease treatment. BTK plays a pivotal role in B-cell receptor signaling pathways that govern the survival, activation, proliferation, and differentiation of B cells. Inhibiting BTK through small molecules has been a validated approach for addressing B-cell lymphomas and autoimmune conditions. Results from a completed phase 1 trial with healthy individuals conducted by SinoMab in China corroborate EVER001’s high selectivity, superior pharmacokinetic properties, robust target binding, and a safety profile backing continued clinical advancement.
Under an exclusive licensing pact with Sinovent Pharmaceuticals and SinoMab BioScience, Everest Medicines possesses global rights to the development, manufacturing, and sale of EVER001 for renal disease treatment.