Tavneos superior to steroids at reversing severe kidney disease
Findings suggest benefit in patients with low kidney function, kidney failure
Tavneos (avacopan) effectively reverses severe kidney disease associated with ANCA-associated vasculitis (AAV) compared with standard steroid therapy, according to a subgroup analysis of the Phase 3 ADVOCATE clinical trial.
Greater improvements in kidney function with Tavneos were sustained for the two months of follow-up after the treatment stopped.
The findings suggest even AAV patients with worse kidney function, and perhaps those with kidney failure, may benefit from Tavneos, although more research is needed to confirm this, the researchers noted.
The trial’s subgroup analysis was published in Kidney International Reports in the study “Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan.”
In AAV, the immune system abnormally produces anti-neutrophil cytoplasmic autoantibodies, or ANCAs, that target certain immune cells, leading them to be overly activated and damage small blood vessels.
Blood vessel injury in the kidneys is a common manifestation of AAV, with up to 38% of patients developing end-stage kidney disease (kidney failure) within five years.
Tavneos is an approved oral therapy for severe and active microscopic polyangiitis (MPA) and granulomatosis with polyangiitis, the two most common types of AAV.
Originally developed by ChemoCentryx (later acquired by Amgen), Tavneos blocks C5a, a component of the complement system, part of the immune system that goes awry in AAV.
The therapy’s approvals were supported by data from the Phase 3 ADVOCATE trial (NCT02994927), which involved 330 AAV patients, who were randomly assigned to receive either Tavneos or the corticosteroid prednisone plus standard care for a year.
Results showed twice-daily Tavneos was generally safe and outperformed standard corticosteroid treatment in promoting long-term remission and improving kidney function.
Before treatment, 81% of participants had kidney involvement, as assessed by the estimated glomerular filtration rate (eGFR), a validated measure of kidney function. eGFR values below 60 mL/min/1.73 m2 suggest kidney impairment, while values below 15 represent kidney failure.
While most patients with kidney failure were excluded from the trial, a subgroup of 50 participants (27 assigned to Tavneos, 23 to prednisone) started the study with severe kidney impairment, as indicated by an eGFR between 15-20 mL/min/1.73 m2.
One in the Tavneos group had an eGFR value of 14 mL/min/1.73 m2 and one in the prednisone group had a value of 12 mL/min/1.73 m2.
Impact of Tavneos on low kidney function
The new analysis focused on this subgroup to assess the impact of Tavneos on kidney function after a year of treatment.
This subgroup had a comparable mean age to the overall study population (66 vs. 61), but included a higher proportion of patients with newly-diagnosed disease (88% vs. 69%), microscopic polyangiitis (72% vs. 45%), and treated with cyclophosphamide (50% vs. 35%).
After one year, the mean increase in eGFR was significantly greater in Tavneos-treated patients than with prednisone (16.1 vs. 7.7 mL/min/1.73 m2), results showed. Consistent results were seen by six months, with a mean eGFR increase of 11.9 with Tavneos versus 6.1 with prednisone.
Between six months and one year, the improvement in eGFR was statistically significant with Tavneos, but not with prednisone.
A significantly greater proportion of patients in the Tavneos group saw their eGFR values improve by two or more times after a year of treatment compared with those with prednisone (41% vs. 13%).
Likewise, more Tavneos-treated participants had increases in eGFR above 20, 30, and 45 mL/min/1.73 m2, including one whose eGFR rose from 17 to 65 after a year.
After completing the trial, participants were followed for eight weeks (about two months), during which they didn’t receive Tavneos or a matching placebo. That difference in eGFR between the two groups was largely maintained, data from that follow-up showed.
Four patients from each group showed a decline in eGFR, with two in the Tavneos group showing relapsing blood vessel inflammation. One Tavneos-treated patient received dialysis during the one-year treatment versus two in the prednisone group.
Improvements to UACR levels with Tavneos
The researchers also looked at the urinary albumin to creatinine ratio (UACR) levels, whereby higher ratios indicate kidney impairment. They found that kidney function improved more rapidly with Tavneos than prednisone.
After one and four months of treatment, UACR values fell with Tavneos, but increased with prednisone, suggesting worse kidney function. After a year, both groups saw their UACR levels drop by a mean of 62%, consistent with the entire ADVOCATE population, the researchers noted.
Sustained disease remission between six months and a year, as indicated by a Birmingham Vasculitis Activity Score (BVAS) of 0, was achieved by a significantly greater proportion of Tavneos patients than prednisone patients (66.7% vs. 60.9%).
During the treatment period, two relapses were reported in the Tavneos group (7.4%); four were reported in the prednisone group (17.4%).
A total of 25 serious side effects occurred in 13 Tavneos-treated patients (48.1%) and 45 events in 16 prednisone-treated patients (69.6%). The number of side effects, serious side effects, and infections were lower in the Tavneos group than the prednisone group.
These findings highlight that Tavneos “successfully reverses the decline in kidney function to a greater extent than a standard prednisone taper in patients with the most severely impaired kidney function … in whom the kidney prognosis is worst and there is the greatest need to rescue kidney function,” the researchers wrote, adding the therapy “may be helpful in preventing, or at least delaying, dialysis in these patients.”
The positive data also “raise the question of whether use of [Tavneos] could benefit patients presenting with a GFR below 15,” the researchers wrote, adding “these patients have the highest risk for end stage kidney disease and mortality, and are in need of effective therapies that reduce these risks and their downstream consequences.”
They said more research on this more severe subgroup is needed to test that hypothesis.
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