AstraZeneca drops MASH drug over disappointing phase 2 data

AstraZeneca has ended work on one of its potential drugs for fatty liver disease after viewing disappointing data from a phase 2 study.

The U.K.-based pharma had been evaluating the antisense oligonucleotide, dubbed AZD2693, in a phase 2b study of patients with metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis.

The study had been due to read out in the third quarter of the year, but AstraZeneca disclosed in its third-quarter earnings documents (PDF) this morning that the trial has been “discontinued due to efficacy.”

Dropping AZD2693 is unlikely to impact AstraZeneca’s wider MASH ambitions, however. The company also has a phase 1-stage GLP-1 agonist that’s being assessed for the liver disease as well as a FAP inhibitor called AZD2389 that’s due to read out later this year.

The other phase 2 asset AstraZeneca dropped this morning was less of a surprise. The pharma confirmed it has ended work on a Takeda-partnered drug for multiple system atrophy, a rare condition that's caused by a loss of nerve cells in the brain.

Takeda had been assessing the alpha-synuclein antibody, called TAK-341 or MEDI1341, in a global study of 159 patients. But the Japanese drugmaker revealed last week that the study failed to hit its primary or secondary endpoints.

Further back in AstraZeneca’s pipeline, the company disclosed today that it has ended work on two phase 1-stage oncology assets “due to strategic portfolio prioritisation.”

One of these was AZD0022, an oral KRASG12D inhibitor that was being assessed in an early-stage study of 430 patients with colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer.

The other was AZD9829, an anti-CD123/TOP1i antibody-drug conjugate being evaluated in patients with acute myeloid leukemia and myelodysplastic syndromes.

While AstraZeneca has tasted ADC success with Daiichi Sankyo thanks to Enhertu and its follow-up Datroway, the U.K.-based Big Pharma has decided to go it alone as it explores the next generation of ADCs.