Adding Tavneos leads to fewer side effects in GPA, MPA patients: Data
Use of therapy as add-on may allow for reduced need for glucocorticoids
Adding Tavneos (avacopan) to standard treatment for the two main types of ANCA-associated vasculitis (AAV) results in fewer adverse events — including a lesser number of serious side effects and infections — in adults with granulomatosis with polyangiitis, or GPA, and microscopic polyangiitis, known as MPA.
That’s according to a new analysis of safety data from two Phase 2 clinical trials — CLEAR (NCT01363388) and CLASSIC (NCT02222155) — and a Phase 3 trial dubbed ADVOCATE (NCT02994927). All three studies had tested the approved oral therapy when added to standard GPA or MPA treatment, with or without the glucocorticoid prednisone.
Glucocorticoids like prednisone are a standard treatment in AAV, but their long-term use is linked to serious side effects. In this analysis, the team was investigating the use of Tavneos as an add-on therapy as a potential alternative to prednisone in treating GPA and MPA.
“In this integrated analysis of safety data from the CLEAR, CLASSIC, and ADVOCATE trials, [Tavneos] demonstrated a favorable safety profile compared with standard treatment with a prednisone taper,” in which clinicians gradually lower a patient’s dose of the glucocorticoid, the researchers wrote.
The analysis, “Safety of Avacopan for the Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Combined Data From Three Clinical Trials,” was published in ACR Open Rheumatology, a journal of the American College of Rheumatology. The work was funded by Chemocentryx, which originally developed Tavneos before being acquired by Amgen.
Investigating the safety of Tavneos vs. glucocorticoids
The inflammation and damage in small blood vessels that mark AAV are partly driven by the complement pathway, a part of the body’s immune response that becomes overly active in AAV.
Tavneos is an oral therapy that suppresses the complement system by blocking the receptor protein of C5a, a complement protein. This is expected to reduce inflammation around small blood vessels, protecting them from damage and easing symptoms of AAV.
The medication is approved in the U.S., the European Union, and several other countries as an add-on to standard AAV treatment for adults with severe, active GPA and MPA. Standard medication typically involves rituximab or cyclophosphamide, along with glucocorticoids.
Tavneos’ approvals were mainly based on data from ADVOCATE, in which the add-on therapy was found to work better than prednisone at promoting long-term remission and improving health-related quality of life while helping to reduce glucocorticoid use.
To gain a clearer understanding of how safe the therapy is, a team of researchers — including one from Amgen — pooled data from the three Tavneos trials, CLEAR, CLASSIC, and ADVOCATE.
Of the 439 patients involved in those studies, 239 received Tavneos and 200 did not. At the time of screening, the patients had an average age of 60.2 and had been diagnosed with AAV for an average of 22 months, or nearly two years. More than half of the participants (57.5%) were men.
All of the patients were on standard treatment with cyclophosphamide or rituximab. All of those not on Tavneos-based regimens, as well as some of those given that medication, also received a prednisone taper, in which the dose was reduced to zero over 20 weeks, or about 4.5 months.
Fewer serious adverse events, infections seen vs. prednisone
Pooled data showed that patients were treated with Tavneos for a total of 212.3 patient-years, while non-Tavneos treatment regimens were given for 195.7 patient-years. Person-years account for the number of patients studied and the time each was observed; for example, 100 person-years could mean 100 patients were studied over one year.
The group of patients treated with Tavneos had significantly lower rates of overall adverse events (1,099.8 vs. 1,251.7 per 100 patient-years) compared with the non-Tavneos group. They also experienced fewer serious adverse events (70.7 vs. 91.5), infections (142.2 vs. 166.6), and low white blood cell counts (22.6 vs. 34.2), the data showed.
These results suggest a favorable benefit-risk profile for [Tavneos] and support the … recommended the use of [this therapy] to reduce glucocorticoid exposure in patients with GPA or MPA.
Both groups had nearly the same rate of adverse events leading to treatment discontinuation and serious adverse events resulting in hospitalizations.
The proportion of patients experiencing serious adverse events related to the liver was numerically, but not significantly, higher in the Tavneos group (4.4% vs. 2.8%). In most of these cases, treatment was paused or stopped (70% vs. 50%). All liver-related problems were resolved.
The findings suggest that, “compared with standard [non-Tavneos] treatment, the use of [the therapy] with a reduced-dose glucocorticoid regimen was associated with a lower incidence of [side effects], [serious side effects], and infections,” the researchers wrote. “These benefits were likely due to the reduced exposure to glucocorticoids in the [Tavneos] versus [non-Tavneos] group.”
The team noted that “no new safety signals have been identified since [Tavneos] became commercially available, and its safety continues to be closely monitored.”
Overall, according to the researchers, “these results suggest a favorable benefit-risk profile for [Tavneos] and support the … recommended the use of [this therapy] to reduce glucocorticoid exposure in patients with GPA or MPA.”
An ongoing Avacostar observational study (NCT05897684) and a placebo-controlled Phase 4 trial (NCT06072482) “will provide a greater understanding of the long-term safety of [Tavneos] in patients with GPA or MPA,” the team concluded.
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