Uplizna is first drug FDA-cleared for rare disease IgG4-RD

Amgen has bagged a second indication for its B cell-depleting therapy Uplizna after the FDA cleared it for rare inflammatory disease IgG4-related disease (IgG4-RD).

Acquired as part of its $27.8 billion takeover of Horizon Therapeutics in 2023, CD19-targeting Uplizna (inebilizumab) is the first treatment to be approved in the US for IgG4-RD, a progressive disease causing inflammation and fibrosis (scarring) in multiple organ systems in the body and which affects around 20,000 people in the US.

It is characterised by unpredictable flares in which the disease progresses and can lead to organ failure, followed by periods of remission. It typically strikes between the ages of 50 and 70 and is more common in men than women. It is, however, very hard to diagnose as its scattergun impact on organs can mimic other diseases.

Uplizna was approved for the rare eye disease neuromyelitis optica spectrum disorder (NMOSD) in 2020 and is also being prepared for an FDA filing in autoimmune disorder generalised myasthenia gravis (gMG), which the company has said is key to its multibillion-dollar sales hope for the drug. Sales reached $379 million last year.

The approval in IgG4-RD is based on the results of the 135-subject MITIGATE study, in which treatment with Uplizna led to an 87% reduction in the risk of flares compared to placebo over 52 weeks of follow-up.

The drug also hit the target on a number of secondary measures, including the annualised flare rate – coming in at 0.1 versus 0.71 for placebo – as well as flare-free, treatment-free complete remission and flare-free, corticosteroid-free complete remission.

MITIGATE lead investigator John Stone welcomed that the IgG4-RD community finally has an FDA-approved therapeutic that targets the underlying disease mechanism.

"Now, our work begins in raising awareness of this disease so that patients can access the right treatment as early as possible, avoiding a long and often harmful diagnostic journey," he added.

For Amgen, the new approval for Uplizna is timely as the drug starts to face increased competition in NMOSD from rival drugs, notably AstraZeneca's long-acting complement C5 inhibitor Ultomiris (ravulizumab), which was approved by the FDA for the eye disorder last year.

Approval in gMG is viewed as the key inflection point for the brand, however, as it would open up a market larger than the other two indications combined in terms of the number of patients in the US eligible for treatment.