Povetacicept

Nearing a pivotal readout for its APOL1-mediated kidney disease (AMKD) candidate, Vertex shared mid-stage data suggesting inaxaplin could benefit a range of patients. However, while the drugmaker's own stock didn't move much on the readout, shares in its kidney disease competitor Maze Therapeutics jumped on Tuesday as investors seemed to favour its rival APOL1 inhibitor.The readout for inaxaplin comes as Vertex is projecting for its renal business to eventually surpass its flagship cystic fibrosis franchise. The drugmaker's lead renal programme, the dual APRIL/BAFF inhibitor povetacicept, is under FDA review for IgA nephropathy with a Nov. 30 PDUFA date (see – Spotlight On: Vertex's renal pipeline approaches an inflection point).While inaxaplin is still in development, Vertex thinks it could be headed towards an accelerated approval. The company has finished enrolment in the Phase II/III AMPLITUDE study in patients with AMKD, severe proteinuria and no other kidney disease-causing comorbidities; results from an interim analysis are expected early next year.The data shared Tuesday, however, were generated in the Phase IIb AMPLIFIED study, which studied the small-molecule APOL1 inhibitor in two distinct AMKD patient populations not included in AMPLITUDE: individuals with modest proteinuria, and those with type 2 diabetes.Altogether, the AMKD populations addressed in the two studies comprise about 250,000 patients in North America and Europe, Vertex has said. 'Two shots on goal'AMPLIFIED was designed to evaluate mean percent change, from baseline to week 13, in urine albumin to creatinine ratio (UACR) as the primary endpoint, with the key secondary measure looking at mean percent change in urine protein to creatinine ratio (UPCR) at the same timepoint. The trial enrolled 23 people with modest proteinuria — defined as UACR levels between 0.1 g/g and 0.42 g/g — and 18 people with type 2 diabetes.In the first cohort, adding inaxaplin to standard-of-care treatment led to 42.7% and 44.7%  reductions in UACR and UPCR, respectively, in patients with modest proteinuria. The result surpassed a bar set by Oppenheimer analysts, who predicted earlier this year that UACR reductions would likely need to exceed 30% to justify further development, adding that they "view the two cohorts as two shots on goal."Inaxaplin's impact in patients with diabetes, however, was more modest. At week 13, participants in the cohort achieved UACR and UPCR reductions of 17.3% and 25.4%, respectively. "The modest proteinuria cohort…delivered remarkable reductions in proteinuria," said Carmen Bozic, Vertex's chief medical officer and EVP, global medicines development and medical affairs. "We are also excited with the treatment effect, though smaller in magnitude, in the type 2 diabetes cohort. We look forward to discussing the AMPLIFIED results with regulators in the context of the AMPLITUDE pivotal study." If the AMPLITUDE data are positive, they could support FDA accelerated approval, Vertex said. Competition loomsWhile the AMPLIFIED data are difficult to compare with findings from a mid-stage AMKD study of Maze's dual-mechanism APOL1 inhibitor given differences in patient populations, that didn't stop investors from sending the biotech's shares up nearly 27% Tuesday. MZE829, which blocks both pore formation and channel function in kidney podocytes, is being studied in the Phase II HORIZON trial involving diabetic and non-diabetic patients, as well as non-diabetics with severe focal segmental glomerulosclerosis (FSGS). "Most" participants in AMPLIFIED's modest proteinuria cohort were not diagnosed with FSGS, Vertex said. Maze reported in March that across all patients in HORIZON, MZE829 was associated with an average 35.6% UACR decrease at 12 weeks from baseline. In patients with diabetes, five were evaluable for efficacy, with two achieving at least a 30% reduction in UACR.

Eric Dube, Ph.D., the CEO who rebranded Travere Therapeutics and oversaw the launch of its rare kidney disease drug Filspari, will step down . Bradley Campbell, who led Amicus Therapeutics until its recent $4.8 billion acquisition by BioMarin , will become Travere’s new CEO on Dec. 1, 2026. Dube will continue to serve as executive advisor through Feb. 15, 2027, to support an orderly transition, Travere said Monday. Dube is leaving after a nearly eight-year tenue to “focus on his health and family,” according to Travere. “My own experiences with rare disease have also given me a profound appreciation for health, family and time,” Dube said in a statement. “After considerable reflection, I’ve decided this is the right moment for me to step away from full-time operating roles and devote greater attention to those priorities.” In a LinkedIn post , Dube reflected on his experience as a two-time survivor of rare cancer, first diagnosed more than 20 years ago. “Patients and families remind us every day how precious health, family and time are. And yet those of us who devote ourselves to serving and advocating for others can become so committed to the mission that we sometimes sacrifice those very things in our own lives,” he wrote. “I’ve decided it’s time for me to listen more closely to that lesson.” About a year after becoming CEO, Dube installed the Travere name to disassociate the company then known as Retrophin from its founder, “pharma bro” Martin Shkreli. In 2023, the company won an FDA accelerated approval for its immunoglobulin A nephropathy (IgAN) medicine Filspari. The drug received its full approval in 2024 and went on to snag the first FDA approval for another rare kidney disease, focal segmental glomerulosclerosis (FSGS), this April. “We have built a company, leadership team and culture capable of carrying this mission forward well beyond any one person. That gives me tremendous confidence that this is the right time—for Travere and for me,” Dube wrote in the LinkedIn post. Taking the baton from Dube, Campbell comes with more than 20 years of experience in the rare disease field. He joined Amicus in 2006 and succeeded founder and long-time helmsman John Crowley in 2022. Travere’s board hired Campbell after a “thoughtful and comprehensive search process focused on the experience and leadership qualities required for the company’s next chapter,” chairman Gary Lyons said in a statement. “Bradley stood out for his unique combination of scientific, commercial and operational expertise, his proven ability to scale innovative rare disease therapies and advance clinical pipelines, and his track record of significant growth and value creation.” During Campbell’s tenure, Amicus graduated from a single-product company in 2023 after scoring FDA approval for its Pombiliti + Opfolda regimen for Pompe disease. In his statement, Campbell touted Travere’s commitment to the rare disease community, its culture and progress. “I see an exciting opportunity to build on that momentum, reach more people living with rare disease and continue creating meaningful value for all stakeholders,” Campbell said. Campbell is inheriting Travere on a growth trajectory. In the second quarter, U.S. sales of Filspari nearly doubled year over year to $141 million, as its initial FSGS launch progress outperformed analysts’ expectations. Meanwhile, the IgAN market is getting increasingly competitive. In 2023, Filspari became just the second IgAN drug approved by the FDA. With an FDA target action date of Nov. 30, 2026, Vertex’s povetacicept is now slated to become the seventh. The San Diego biotech recently expanded its pipeline, paying $112.5 million upfront for an oral BTK inhibitor called civorebrutinib from China’s Everest Medicines for development in immune-mediated kidney diseases.