FDA Approves Tavneos as Add-on Therapy for Severe MPA, GPA
The U.S. Food and Drug Administration (FDA) has approved Tavneos (avacopan) as an add-on therapy for people with severe active microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), the two most common forms of ANCA-associated vasculitis.
The approval comes after an advisory committee narrowly supported avacopan’s approval in the U.S., prompting ChemoCentryx to file an amended application with additional data.
Tavneos is the first approved treatment for AAV in over a decade, and marks the first FDA approval of an oral complement 5a receptor inhibitor for AAV.
“Today is a momentous day in the history of ChemoCentryx; the culmination of decades of effort aimed at offering new hope to patients with this and other debilitating and deadly diseases,” Thomas J. Schall, PhD, president and CEO of ChemoCentryx, said in a press release.
Tavneos’ approval was based on findings from the pivotal ADVOCATE Phase 3 clinical trial (NCT02994927), which showed Tavneos to be an effective alternative to prednisone — a standard corticosteroid treatment for AAV that is often linked with side effects.
These data also supported Tavneos’ approval in Japan for the treatment of MPA and GPA. A decision on a similar application in Europe is expected by year’s end.
“I am excited that our work has helped lead to the first-in-a-decade approval of a medicine for ANCA-associated vasculitis. This is an important step forward in the treatment of this disease,” said Peter A. Merkel, MD, one of the trial’s investigators, who serves as the director of the international Vasculitis Clinical Research Consortium, and as a consultant to ChemoCentryx.
“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” added Merkel, who also is chief of rheumatology at the Perelman School of Medicine at the University of Pennsylvania.
The complement system, a part of the immune system that normally helps to fight infections, may also play a role in autoimmune diseases like AAV.
Tavneos is an oral small molecule that inhibits the receptor of the C5a protein, one of the most potent pro-inflammatory proteins of the complement system. By blocking C5a signaling, the therapy is thought to lessen inflammation and blood vessel damage caused by excessive complement activation.
ADVOCATE was an international clinical trial into the safety and efficacy of Tavneos in adults with GPA and MPA. It enrolled 330 patients across 20 countries, who were randomly assigned to Tavneos or a standard regime of the glucocorticoid prednisone for about one year.
All patients also received standard immunosuppressive medications — rituximab or cyclophosphamide, followed by azathioprine. Patients in both arms could also receive other glucocorticoids, if needed.
The study met its primary efficacy goals, demonstrating that the therapy was similar to at inducing clinical remission after six months (72.3% among avacopan-treated patients, and 70.1% for those on prednisone), and was significantly better at sustaining that remission at least until the one-year mark (65.7% vs. 54.9%).
Additional data showed that Tavneos was better at improving kidney function, especially among patients with advanced kidney disease at the time of treatment initiation.
The treatment was generally well-tolerated, and with lesser steroid-associated toxicity, consistent with more steroids being used in the prednisone group.
Common adverse reactions more frequently reported in the Tavneos group included nausea, headache, high blood pressure, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, increase in blood levels of creatinine (indicating poor kidney function), and prickling sensation.
ChemoCentryx developed a patient support program, called Tavneos Connect, to assist people who are prescribed this medication in the U.S. More information is to become available here.
“We look forward to making Tavneos available to clinicians and patients in the next few week,” Schall said, thanking “the pioneering scientists, clinicians and patients who believed in the promise of Tavneos and who have worked tirelessly to make it a reality.”