Final trial data confirm effectiveness of now-approved IgAN treatment
Injection therapy works to slow kidney disease progression in adults
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The final results of a large clinical trial show the approved IgAN therapy Trutakna can slow kidney disease progression. (Image from iStock)
Treatment with Trutakna (atacicept-vymj) can slow the decline of kidney function in people with immunoglobulin A nephropathy (IgAN), according to the final results of a late-stage clinical trial whose data were used to secure the therapy’s conditional clearance in the U.S.
Trutakna, developed by Vera Therapeutics, was approved by the U.S. Food and Drug Administration earlier this year for adults with IgAN who are at risk of disease progression. That approval was based on eight-month data from the Phase 3 ORIGIN 3 trial (NCT04716231), run at a single center in California.
The FDA’s decision was specifically predicated on trial findings that the injection therapy reduced protein in the urine, a marker of kidney damage.
Now, two-year results from the large trial confirm the therapy’s beneficial effects on kidney disease progression — data required for Trutankna to be potentially granted full regulatory approval in the U.S. Vera is planning to use these data as a basis to submit a supplemental biologics license application (BLA) asking the FDA to convert the current accelerated approval to a full approval.
“We plan to submit the supplemental BLA [between October and December] of this year,” Marshall Fordyce, MD, founder and CEO of Vera, said in a company press release. “We look forward to the potential full approval of Trutakna in 2027.”
The company said it plans to present detailed findings from this final efficacy analysis at a future scientific meeting.
IgAN is an immune disorder marked by the buildup of a specific type of antibody in the kidneys, leading to kidney damage. Trutakna works by blocking the activity of two immune signaling molecules — a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) — that are thought to play central roles in the production of disease-driving antibodies. The therapy is administered once weekly by injection under the skin.
“We believe that upstream [suppression] of BAFF and APRIL with Trutakna achieves results that reflect the potential for comprehensive disease modification in IgAN,” Fordyce said.
Trial tested Trutakna vs. a placebo in over 400 patients
The final top-line results from the ORIGIN 3 study covered 428 patients who were randomly assigned to receive either Trutakna or a placebo for as long as two years. Kidney function was tracked by calculating the estimated glomerular filtration rate (eGFR), a standard measure that reflects how efficiently the kidneys filter blood; it is expressed in milliliters per minute per 1.73 square meters (mL/min/1.73 m2).
At the end of the study’s first year, the average eGFR decrease, indicating worsening, was significantly lower in the Trutakna group than in the placebo group (0.1 vs. 5.7 mL/min/1.73m2).
After two years, the medication’s use was associated with a significantly lower annual eGFR decline rate (0.6 vs. 5.6 mL/min/1.73m2). Vera noted that Trutakna’s beneficial effects align with treatment goal guidelines aimed at reducing the annual eGFR decline rate to a healthy rate (fewer than 1 mL/min/1.73m2).
Prevention of kidney failure or kidney-related death is the ultimate goal. … We now have evidence suggesting that Trutakna may help patients avoid dialysis, [a transplant], or kidney-related death over the long term.
Over the two years, none of the participants given Trutakna needed dialysis (a kidney replacement therapy) for 30 days or more, underwent a kidney transplant (reflecting kidney failure), or died, the data showed. By contrast, in the placebo group, eight people experienced at least one of these adverse outcomes.
Treatment with Trutakna versus the placebo resulted in a significant reduction, by 76%, in the risk of experiencing a composite kidney disease progression event. While the release did not specify the elements of this composite outcome, it most likely includes the above-mentioned adverse outcomes and specific eGFR changes that reflect kidney disease progression.
“Prevention of kidney failure or kidney-related death is the ultimate goal,” said Richard Lafayette, MD, principal investigator of ORIGIN 3 at Stanford University Medical Center. “We now have evidence suggesting that Trutakna may help patients avoid dialysis, transplantation, or kidney-related death over the long term.”
Rates of infections and other safety issues were comparable between patients receiving Trutakna and those given the placebo.
“The ORIGIN 3 final analysis, demonstrating a significant reduction in risk of composite kidney disease progression, true stabilization of eGFR, and a favorable safety profile through two years, marks a milestone in IgAN treatment,” Lafayette said.
300-plus drug start forms seen in first 10 weeks
Trutakna won its FDA approval in July for use in reducing urine protein levels in at-risk adults with IgAN.
“Since receiving accelerated approval, we have seen significant interest from the IgAN community,” said Matt Skelton, Vera’s chief commercial officer. “In the first ten weeks, we have generated over 350 patient start forms. We are seeing paid claims and are pleased with initial payer policies.”
Vera offers a patient support program, called Trutakna TRU SUPPORT, that helps individuals prescribed the medication navigate insurance coverage options. The program also offers financial support for eligible patients and provides nurse educator support for treatment administration.
