Tavneos’ use by AAV patients prior to approval support its safety
Study looks at 30 patients treated in 2019-21 under extended access
Tavneos (avacopan) was generally safe and well tolerated in adults with severe ANCA-associated vasculitis treated under a global early access program (EAP) before the therapy’s approval, a study showed.
EAPs make investigational therapies available outside clinical trials to people with serious or life-threatening conditions who have few or no adequate treatments, and when the therapy’s potential benefits are thought outweigh its potential risks.
Notably, Tavneos’ safety profile was comparable to that reported in the clinical trials that led to regulatory approvals — in the U.S. and Japan in 2021 and Europe in 2022 — for adults with severe active microscopic polyangiitis and granulomatosis with polyangiitis, the two most common forms of AAV.
The study, “Preliminary Assessment of Safety and Tolerability of Avacopan During the Early Access Program for ANCA-Associated Vasculitis,” was published in Dovepress.
Safety profile seen to be ‘consistent’ with clinical trials of Tavneos
AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels. This disease is caused by abnormal antibodies, called anti-neutrophil cytoplasmic autoantibodies or ANCAs, that target neutrophils, a type of immune cell, turning them excessively active and promoting inflammation.
The complement system, a family of proteins important for normal immune responses, also is overactive in AAV patients.
Immunosuppressive agents, such as rituximab, are common AAV treatments, along with daily anti-inflammatory glucocorticoids or steroids. However, long-term use of steroid medications is frequently associated with significant side effects.
Originally developed by ChemoCentryx and later acquired by Amgen, Tavneos is an oral therapy that works by suppressing the activity of the complement component 5a receptor. As such, it is designed to lessen the AAV-associated inflammation and blood vessel damage caused by excessive complement activation.
Tavneos’ approvals were supported by results from the Phase 3 ADVOCATE trial (NCT02994927), which involved 331 acute AAV patients who were randomly assigned to either Tavneos or the steroid prednisone, plus standard care, for a year.
Results showed that Tavneos was generally safe and superior to steroid treatment at promoting long-term remission and improving kidney function.
Between ADVOCATE’s 2019 completion and the therapy’s approval, 30 adults with AAV (21 men and nine women) were treated with Tavneos over the EAP’s years.
“Eligible for the EAP were patients with new or relapsing life- or organ-threatening ANCA-associated vasculitis, requiring an induction treatment, who also had a high risk of steroid-related complications,” the researchers wrote.
Researchers in the Netherlands and at Vifor Pharma — which holds commercial rights to the therapy outside the U.S. — analyzed Tavneos’ safety within the EAP between Feb. 2, 2019, and Nov. 30, 2021, as recorded in a global safety database.
“Importantly, all physicians managing patients in the EAP had previous experience with [Tavneos] in the ADVOCATE study and were experienced in recognizing [adverse events] and adverse drug reactions,” the researchers wrote.
Most patients were treated in the Netherlands (10 patients) or France (10 patients), with others in Germany, Ireland, the U.K., Switzerland, and Australia. Average duration of Tavneos treatment was 11.5 months, and as of this study’s late 2022 filing, nine still were being treated under the EAP.
No adverse events were reported for most patients (73%), while 24 side effects were reported in eight others (27%). No deaths were reported.
Six serious adverse events (SAEs) in two patients (6.6%) were considered by treating physicians to be related or possibly related to Tavneos’ use. These included acute kidney injury, Klebsiella and staphylococcal bacterial infections, prostate inflammation, and sepsis due to a urinary tract infection during a hospitalization in one person with bladder cancer and a history of urinary infections.
The remaining SAE, a worsening of age-related macular degeneration (an eye condition) in one patient, and two side effects in other patients (a skin reaction and distorted sense of taste) were seen as possibly related to treatment. The person whose taste was affected, a condition called dysgeusia, stopped treatment within three months, the researchers reported.
“Only one SAE of special interest, as defined during the clinical trial program, occurred during the EAP (lymphopenia),” the researchers wrote. Although this patient also stopped treatment, the lymphopenia, or low lymphocyte (an immune cell) counts, was considered to be associated with simultaneous rituximab use rather than Tavneos.
Four other patients discontinued treatment within three months for side effects considered unrelated or for unknown reasons.
Overall, “no new or elevated safety signal was observed,” the researchers wrote, adding that Tavneos’ safety profile was “consistent” with that seen in its trials.
“Per the experience from the clinical trials of [Tavneos] in patients with ANCA-associated vasculitis, the most frequently reported SAEs were infections and [kidney] disorders,” they added. Kidney failure was noted in one person after two months of treatment but not considered related, as this patient had a history of dialysis use and had refused steroid treatment.
Considering the small number of patients and the study’s short observation period, however, “it is important that pharmacovigilance surveillance remains ongoing when [Tavneos] gains global market access as treatment for ANCA-associated vasculitis,” the team concluded.