On July 2, Everest Medicines (1952.HK), a Hong Kong-listed innovative pharmaceutical company, announced that its new generation of covalent reversible Bruton's tyrosine kinase (BTK) inhibitor EVER001 (XNW1011), for which it has global rights, has obtained positive latest interim data in a Phase 1b/2a clinical trial for the treatment of primary membranous nephropathy (pMN). The data showed that EVER001 continued to demonstrate excellent efficacy and safety during the extended follow-up period.
Driven by these excellent clinical data, the development of EVER001 is expected to accelerate. Based on the current positive clinical data, experts recommend communicating directly with the U.S. Food and Drug Administration (FDA) to initiate Phase III clinical studies, and simultaneously communicate with the China Food and Drug Administration (CDE).
Clinical trial data highlights frequently, with both effectiveness and safety

According to reports, the Phase 1b/2a clinical trial of EVER001 for the treatment of primary membranous nephropathy conducted in China is an open-label study designed to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of EVER001 in Chinese patients with glomerular diseases characterized by proteinuria. A total of 31 patients with primary membranous nephropathy who were confirmed by renal biopsy to be positive for anti-PLA2R autoantibodies were enrolled in the low-dose group and the high-dose group, and received EVER001 treatment for a total of 36 weeks.
The clinical trial data published this time covers the longer-term follow-up results of more patients as of March 21, 2025. Among them, 11 patients in the low-dose group were followed up to 52 weeks, and 16 and 12 patients in the high-dose group completed 24 weeks and 36 weeks of treatment, respectively, and 7 patients were followed up to 52 weeks.
The data showed that in terms of immunological indicators, the levels of anti-PLA2R autoantibodies in both cohorts decreased significantly at an early stage compared with the baseline. At 12 weeks, the LS geometric means of the low-dose group and the high-dose group decreased by 62.2% and 87.3%, respectively; at 24 weeks, the decline in both groups increased to more than 93%, of which 76.9% of the low-dose group patients and 88.2% of the high-dose group patients achieved complete immunological remission.
Clinical remission indicators also performed well. At 24 weeks, the LS geometric mean of 24-hour proteinuria decreased by 57.0% and 67.6% in the low-dose group and the high-dose group, respectively; at 36 weeks, the reduction increased to 76.7% and 80.6%, respectively, and was maintained until week 52. At 24 weeks, 38.5% of patients in the low-dose group and 70.6% of patients in the high-dose group achieved clinical remission. At 36 weeks, this proportion rose to 69.2% and 91.7%. During the treatment, the average serum albumin level of patients in both dose groups reached the normal range, and renal function remained stable.
Overall, EVER001 is safe and well tolerated, consistent with previous observations. The vast majority of reported adverse events were grade 1 or 2, and no clinically significant adverse events commonly seen with other covalent non-reversible BTK inhibitors, such as bleeding, arrhythmias, serious infections, and severe liver damage, were observed. These data further show that EVER001 is effective and well tolerated in patients with primary membranous nephropathy, supporting the potential of EVER001 to treat autoimmune glomerular diseases characterized by proteinuria.
At the latest clinical data interpretation meeting of EVER001 held by Everest Medicine on June 30, Professor Richard Lafayette, Professor of Medicine at Stanford University, founder and director of the Stanford Glomerular Disease Center, and member of the Glomerular Disease Committee of the American Society of Nephrology, highly affirmed the clinical value of EVER001.
He pointed out that existing drugs for treating autoimmune kidney disease have deficiencies in safety and efficacy, and the BTK inhibition mechanism is expected to replace traditional therapies. As a new generation of BTK inhibitors, EVER001 has better targeting and tolerability in molecular design, and has the advantage of oral convenience. "So far, EVER001 has not shown a trend of more serious adverse events or infections. The high-dose group has better inhibition of specific antibodies and can quickly treat PLA2R antibody-mediated membranous nephropathy, almost achieving a complete response. This makes people feel that this drug is very exciting compared to current treatment options," he said.
Regarding this positive clinical trial result, Everest Medicines CEO Luo Yongqing said, "The latest data results of the Phase 1b/2a study of EVER001 still show encouraging immunological remission and clinical remission, as well as good safety and tolerability. As a new generation of BTK inhibitor, EVER001 has the advantages of covalent reversibility, good selectivity, strong target binding ability, and less off-target toxicity, and has great potential for the treatment of various autoimmune kidney diseases including primary membranous nephropathy. We will continue to accelerate the global clinical development of EVER001 in order to meet the urgent clinical needs of patients more quickly."
Focusing on global unmet needs, clinical development is expected to accelerate
Primary membranous nephropathy is a common pathological type of nephrotic syndrome in adults. Its prevalence in my country is increasing year by year, and it is the primary glomerulonephritis with the second highest incidence after IgA nephropathy. Currently, there are no drugs approved for this indication in the world, and existing therapeutic drugs (such as cyclophosphamide, calcineurin inhibitors, and CD20 monoclonal antibodies) are all used off-label. More than one-third of patients with primary membranous nephropathy will eventually progress to end-stage renal disease. The world is in urgent need of developing therapeutic drugs that can improve the remission rate of treatment, reduce the high recurrence rate, and reduce the risk of chronic nephrotoxicity.
Professor Richard Lafayette pointed out that currently, the off-label drugs commonly used in clinical practice have obvious limitations. For example, hormones and cyclophosphamide may increase the risk of long-term cancer and short-term serious infection; although the response rate of calcineurin inhibitors is high, they need to be maintained for a long time, and the risk of recurrence is high within less than one year after withdrawal, and it may cause metabolic complications such as diabetes, hypertension and kidney damage; although anti-CD20 therapy is effective in 60% of patients in the best trials, it will lead to irreversible B cell clearance within 6-9 months, and patients face long-term immune damage and infection risks, and need to be closely monitored.
"We need not only second-line drugs to treat patients who are currently unresponsive or who have relapsed, but we also need first-line oral drugs that are easy to use and can be discontinued if patients have any concerns," said Professor Richard Lafayette.
It is reported that as a new generation of BTK inhibitor, the core advantages of EVER001 lie in its reversible mechanism and oral convenience. Patients can stop taking the drug at any time to restore their immunity, avoiding the off-target side effects of other BTK inhibitors. It also has fast onset of action, deep relief, and strong durability, and can effectively fill the current treatment gaps.
In addition to primary membranous nephropathy, EVER001 also has potential in other autoimmune kidney diseases, including IgA nephropathy, minimal change nephropathy, focal segmental glomerulosclerosis and lupus nephritis. The potential patient population exceeds 10 million, indicating that EVER001 is expected to become another blockbuster renal drug.
Professor Richard Lafayette added, "There are a lot of unmet clinical needs in the field of autoimmune kidney disease. Existing therapies are insufficient in terms of safety and efficacy. For almost all autoimmune kidney diseases, we currently treat them with rituximab, cyclophosphamide and even mycophenolate mofetil, and BTK inhibitors may replace them in the future. This means that hundreds of thousands of patients in the United States and millions of patients worldwide may benefit."
As a potential best-in-class product, the subsequent global development progress of EVER001 has attracted widespread attention in the industry.
"Based on the current positive clinical data, experts recommend communicating directly with the U.S. Food and Drug Administration to initiate Phase III clinical studies, and simultaneously communicate with the China National Medical Products Administration." Professor Richard Lafayette also believes that the Phase III study design, which focuses on two-year complete remission rate and safety, is reasonable, and the potential of EVER001 is worth advancing and verifying. This suggestion undoubtedly provides a clear direction for the rapid advancement of EVER001, and also makes people look forward to the early launch of the drug.
In addition, the huge unmet clinical needs are expected to catalyze the overseas licensing of EVER001. Given the excellent clinical data of EVER001, brokerages generally expect that it has great potential for overseas licensing. "At present, we are communicating with many parties. If the concept of EVER001 can be verified and can be transferred to key studies, I believe that many companies, especially those in the fields of kidney disease and immune disease, will join in."

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