There was not much for us to report on this summer that would interest our readership…
Let’s skip the Fauci / Paul senate drama regarding the origins of Covid, with senator Paul taking the role of the Grand Inquisitor and Dr. Fauci the Fifth. The latest act in this screen play introduced no new facts, only a bit of human hubris. The senate dialogue – or monologue in this case – sounded like a 1950s House Un-American Activities Committee (HUAC) hearing. No new facts for sure.
The second and more entertaining summer show is still going on; Amgen’s handling of avacopan / TAVNEOS. Unless you live behind the hills, you certainly heard about Chemocentryx and how they reportedly misrepresented the outcome data from the pivotal ADVOCATE trial in ANCA vasculitis. Much of this was uncovered only after approval. When the FDA learned late last year that the company had ‘re-adjudicated’ the original data, it threatened withdrawal of the drug.
Detective work by consultant Dr. Walden identified the scheming machinations of some C-suite actors who had hidden the original non-inferior non-superior outcome results, thereby snatching victory from the jaws of defeat. The Walden report is not in the public domain to the best of our knowledge. We have to take the FDA’s word for it, as regards the sequence of events around the time of unblinding and the role played by statisticians, the Adjudication Committee (AC), and company execs.
Several regulatory agencies worldwide reacted to the new information by rescinding the TAVNEOS approval (EMA, TSA, others), but not so the FDA which appears strangely ambivalent, almost benevolent. While FDA provided a multi-page explanation why TAVNEOS no longer meets approvability criteria and should be recalled, they offered Amgen an Advisory meeting for final ‘adjudication’. The company since obtained an independent reanalysis of the pivotal study data from DCRI which – surprise! – confirmed that TAVNEOS did not achieve the required superiority at the 1-yr timepoint. Nevertheless, the FDA has taken no action yet.
The NEJM retraction of the 2021 article of the ADVOCATE study was a correct and needed step.[1] Why did they exculpate the 2 academic (sic!) authors of the retracted article by saying that data re-adjudication occurred “without the knowledge of these two authors”. This strikes us as hypocritical. The first author, DRW Joyce, was the head of the independent Adjudication Committee (AC); in that capacity he and others must have been informed of the goings-on, esp. the post-unblinding re-adjudication. While we don’t have all the details, it looks like several people played roughshod with the study’s Stat Plan and the AC charter.
Another interesting statement can be found in a Lancet Editorial entitled ‘The end is near for Avacopan’.[2] The review mentions the controversy surrounding the ADVOCATE study, but emphasizes post-approval trials. The editors conclude that the “totality of the evidence suggests benefit for patients across a range of outcomes”.
How come? What a twisted logic! Is this the new back-door way to get new compounds into patient care? Never mind the outcome of the pivotal trial program, just conduct a series of compelling ‘real-world’ studies and get approval with the support of benevolent experts and patient testimonials.
Avacopan may be a useful drug in some C5 inhibitor indications, but this hypothesis is still unproven. The drug may even have a role to play in ANCA vasculitis, but the ADVOCATE study did not measure up and only showed a trend. Justifying the use of avacopan with post-marketing ‘real-world’ efficacy data is a smoke screen.
The company could have run a second trial in ANCA or trials in PNH. They chose not to. They took a risk, knowing that the drug’s fate would depend on showing superiority at the 52-wk primary endpoint. No ifs, ands or buts. When they saw the unblinded data, they panicked.
We wonder if senator Rand Paul has heard of the avacopan story. If he finds out that Fauci sponsored ‘gain-of-function’ research for avacopan at the Wuhan lab, we will be treated to yet another hot investigation. Just kidding, of course!
Who would have thought that the lazy hot late summer days of 2026 would hold so much entertainment value!
ABBREVIATIONS
ANCA antinuclear cytoplasmic antibody
AC adjudication committee
DCRI Duke Clinical Research Institute
PNH paroxysmal nocturnal hemoglobinuria
TGA Therapeutic Goods Administration (Australia)
REFERENCES
[1] Rubin W. Retraction: Jayne DRW et al. Avacopan for the Treatment of ANCA-Associated Vasculitis, N Engl J Med 2021;384:599 DOI: 10.1056/NEJMe2608684
[2] Editorial. The end for avacopan. The Lancet Rheumatology. Published Online July 10, 2026 https://doi.org/10.1016/S2665-9913(26)00225-0
