While Vertex is laser-focused on an upcoming FDA decision for povetacicept in immunoglobulin A nephropathy, the APOL1 inhibitor inaxaplin has demonstrated potential “best-in-class” data in a different kidney disease.
Vertex Pharmaceuticals’ inaxaplin reduced two key markers of kidney disease in a mid-stage trial, suggesting that the drug could be used in a broad population of patients as investors had hoped and prompting BMO Capital Markets analysts to describe the drug’s “best-in-class” potential.
Future readouts could add weight to Vertex’s potential blockbuster opportunity, but analysts also pointed to key issues, including the small trial population. The results, announced Tuesday morning, arrive as the company awaits an FDA decision for the use of povetacicept in adults with immunoglobulin A nephropathy (IgAN)—a potential approval that could launch Vertex into the renal markets.
The new data come from the highly anticipated Phase 2/3 AMPLIFED study, which was testing the APOL1 inhibitor inaxaplin in 41 patients with APOL1-mediated kidney disease (AMKD). Cohort 1 included 23 patients with the disease who had modest levels of protein in their urine while cohort 2 featured 18 people with AMKD as well as type 2 diabetes (T2D).
For cohort 1, a 45-mg dose of the study drug plus standard of care led to a 42.7% reduction in urine albumin to creatinine ratio (UACR) at week 13 as compared with baseline, which was the primary endpoint of the study. This group also had a 44.7% decrease in urine protein to creatinine ratio (UPCR), a key secondary goal of the trial.
Analysts were more focused on this first cohort, with Stifel and Truist Securities both noting that the results confirm an earlier benefit seen in a much smaller Phase 2a trial of patients with AMKD who had focal segmental glomerulosclerosis (FSGS). In that study, UACR was reduced by 43.4% and UPCR dropped 47.6% at week 13.
“The key debate for VRTX’s inaxaplin program for years has been whether the compelling efficacy observed in the small, ph2a inaxaplin study in APOL1-FSGS . . . would translate to a broader APOL1 population,” Stifel wrote to investors on Tuesday morning.
Today’s readout is “is at the very least incrementally positive for the translatability to a more heterogeneous population,” Stifel continued—while pointing out that Vertex did not disclose the exact number of patients in the cohort that were non-FSGS.
BMO was similarly bullish on the results as evidence of a broader reach for the drug. “Strong inaxaplin efficacy in modest proteinuria expands the potential commercial opportunity for Vertex in AMKD,” the analysts wrote in their own Tuesday morning note.
The benefit in cohort 2 was more modest. UACR was reduced by 17.3% and UPCR declined by 25.4%. The analysts were not surprised by this given that diabetes is a key risk factor for the advancement of chronic kidney disease. Nevertheless, BMO said the “results remain directionally encouraging” in this patient segment and worthy of further exploration.
Rival Maze Therapeutics has also previously tested its APOL1 inhibitor MZE829 in this population and found little response, Stifel said.
Inaxaplin is also being tested in the Phase 2/3 AMPLITUDE trial, which excludes patients with diabetes and is expected to readout in early 2027. If successful, this study could support an accelerated approval, according to Stifel.
The AMPLIFIED data has served as a key derisking event for this upcoming later-stage trial, according to BMO. “With AMPLITUDE fully enrolled and interim data in early 2027, today’s update reinforces inaxaplin’s best-in-class potential.”
With Tuesday’s results opening up a broader segment of the AMKD population, Vertex could have access to an estimated 150,000 patients in the U.S. and Europe if inaxaplin is approved for AMKD, Leerink Partners said. The firm estimated that sales of the drug could reach $1.2 billion in 2035.
“That said, we caveat these results with the fact that AMPLIFIED is single-arm and open-label, n is small, and the 95% CIs [confidence intervals] were generated post-hoc,” Leerink wrote.
Inaxaplin is just one part of Vertex’s envisioned kidney disease portfolio. The FDA is expected to rule on the use of povetacicept in adults with immunoglobulin A nephropathy (IgAN) by November 30.
“Coupled with a potential povetacicept approval later this year, inaxaplin meaningfully diversifies the renal opportunity for Vertex through new therapeutic mechanisms and indications,” BMO wrote.
