Long-awaited news from Amgen about the top-line results from the MITIGATE trial! 

A blue graphic reading "Important Announcement! Amgen announces positive results for Phase 3 Registrational Trial Evaluating Uplizna® (inebilizumab) for treatment of IgG4-Related Disease. IgG4ward!" There are gold megaphones in the bottom left and top right of the graphic.

Back in 2018 – WAY before the pandemic – I had a conversation with a pharmaceutical company called Viela about doing a clinical trial of a medication called “inebilizumab” in IgG4-RD. Inebilizumab can achieve important effects on the immune system by depleting a group of cells called B cells. Viela was intrigued by the idea because nearly ten years earlier, our group at Massachusetts General Hospital (MGH) had reported on the use of another B cell-depleting agent, rituximab, which works by targeting a slightly different protein on the B cell surface.

Rituximab, however, had never been studied in the context of a randomized, double-blind, placebo-controlled trial. The world’s regulatory agencies – the U.S. Food & Drug Administration, the European Medicines Agency, and others – understand that it is only through the conduct of such trials that we can understand whether or not a treatment truly works for a disease, and if it can be administered safely. Viela, which decided to proceed with the trial, was eventually acquired by Horizon which, in turn, was acquired by Amgen. But all through those transactions, the trial that became known as “MITIGATE” proceeded – not faltering even during the COVID pandemic.

Today, fifteen years after we first used a B cell depletion strategy in IgG4-RD, we now have confirmation through MITIGATE – the first such international trial ever performed in IgG4-RD – that this treatment approach of B cell depletion in IgG4-RD is effective. Inebilizumab reduced the risk of disease flare by 87% compared to the standard treatment arm. Our orphan disease now has a therapy that is proven to work.

The MITIGATE trial enrolled patients at no fewer than 80 sites across the world in 22 different countries across North and South America, Asia, Europe, and Australia. As the first clinical trial of its kind, MITIGATE had to overcome multiple hurdles: how many clinical trial patients would need to be studied to prove the point; initial discussions with regulatory agencies about clinical trial endpoints; and the innumerable logistical challenges associated with conducting a clinical study at so many sites across the world. During COVID!

So today’s press release marks a major milestone for people living with IgG4-RD: the successful completion of a phase 3 clinical trial. Much work remains ahead to achieve regulatory approval and to ensure that all patients with IgG4-RD who may benefit from this drug can obtain access to it, but the announcement was a crucial step without which none of the rest would be possible. This day has been a long time coming for people with IgG4-RD, and it is one to celebrate.

Congratulations to the MITIGATE investigators, to Amgen, and most importantly, of course, to the patients who participated in this trial.

More to come from the IgG4ward! Foundation on inebilizumab, IgG4-RD, and the implications of this vitally important trial for people living with IgG4-RD.

You can read the full press release from Amgen here.

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Responses

  1. Congratulations Dr. Stone, and all of the patients and researchers who dedicated themselves to this trial. So much appreciation. This is a monumental day for the community!!! Congratulations IgG4-rd community!!!! 💛💙

  2. There are so many reasons to celebrate this news. Milestone by milestone we are moving closer to the target!

    2024 has proven to be a MONUMENTAL year for us!

    Thank you to all who made this possible!