Medical Innovation Exchange

AstraZeneca axes kidney disease program after seeing phase 2b data, dealing another blow to IL-33

AstraZeneca has cut another strand of its multifront IL-33 drug development program, stopping work in diabetic kidney disease (DKD) in response to phase 2b efficacy data. 

The drugmaker moved tozorakimab, an anti-IL-33 monoclonal antibody, into phase 2b in DKD in 2019 in response to evidence that inflammation plays a role in disease. Biomarkers of inflammation correlate to poor outcomes and mortality, and biopsies show IL-33 is upregulated, fueling hopes that inhibition of the pathway could reduce kidney damage.

AstraZeneca wrapped up the phase 2b, which administered tozorakimab in combination with its kidney disease drug Farxiga, last year and began analyzing whether the investigational molecule improved the urine albumin:creatinine ratio by more than placebo. The company is yet to share the results but used its fourth-quarter earnings to reveal it discontinued the trial because of efficacy.

After seeing the data, AstraZeneca removed tozorakimab in DKD from its phase 2 pipeline. The action was the only removal of a new molecular entity disclosed in the quarterly update, with all the other changes covering life cycle management of approved products. 

AstraZeneca is continuing to advance tozorakimab, also known as MEDI3506, in other indications. The molecule is in two sets of phase 3 studies, one in chronic obstructive pulmonary disease (COPD) and another in viral lung infection and acute respiratory failure. AstraZeneca recently published phase 2 data in asthma and continues to list the indication in its midphase pipeline. 

Talking to investors on a third-quarter earnings call in November, Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, called tozorakimab “a strong contender” that “is differentiated [from] competitors because it is able to inhibit both the ST2 and the RAGE/EGFR pathways.”

AstraZeneca stopped work on the molecule in atopic dermatitis one year ago, and has seen its peers pull back from the target. GSK dropped its candidate in 2019, and the following year Roche axed a candidate aimed at the IL-33 pathway after seeing asthma data. Sanofi and Regeneron pushed back a setback in phase 2 and powered into a pivotal program in COPD.

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