AstraZeneca dumps $855M, near-approval rare disease drug after talks with regulators

AstraZeneca has dumped a rare disease drug candidate once considered worth $855 million after chalking up a pair of phase 2 flops, despite the prospect previously hitting the mark in a much larger phase 3 trial. The drugmaker disclosed the action alongside news of the jettisoning of a nonalcoholic steatohepatitis (NASH) therapy.

Alexion paid $855 million to acquire Wilson Therapeutics and take control of its phase 3 asset WTX101, now known as ALXN1840, in 2018 as it sought to rebuild its pipeline after some M&A misadventure left it lacking a path to growth beyond Soliris. Evidence of the success of the plan emerged last year when AstraZeneca, having bought Alexion for $39 billion, revealed a phase 3 trial hit its primary endpoint.

At the time, AstraZeneca said that “two ongoing mechanistic trials in Wilson disease are also underway” and that Alexion was “working closely with health authorities worldwide” and intended “to submit these data for review.” Ten months later, AstraZeneca has removed ALXN1840 from its clinical-phase pipeline. As recently as February, AstraZeneca was predicting (PDF) that it would file for approval in the second half of 2023. However, the Anglo-Swedish Big Pharma has since learned that two phase 2 trials missed their primary endpoints. 

In a first-quarter earnings call with journalists, AstraZeneca Chief Financial Officer Aradhana Sarin described how the company had dropped (PDF) ALXN1840 “based off results of phase 2 mechanistic studies and discussions with regulatory authorities.”

CEO Pascal Soriot expanded on the decision, explaining that the phase 2 studies had not been able “to show that copper was actually eliminated from the body.”

“You may be facing a situation where copper is actually redistributed to all the organs, all the parts of the body,” the CEO said on the call. “We could have continued to invest and try to do more research, but we felt it was going to be a long shot, it was going to be taking too much time.”

One phase 2 study enrolled nine patients and had a primary endpoint of mean daily copper balance. The other trial recruited 31 participants and had a primary endpoint of change from baseline at Week 48 in liver copper concentration. Neither study met its primary endpoint. 

This morning's earnings update (PDF) also saw AstraZeneca clear the GLP-1/glucagon dual agonist cotadutide from its phase 2 pipeline. AstraZeneca took the candidate into a phase 2/3 NASH trial last year but recently revealed it stopped enrollment after recruiting 45 patients, well short of the targeted 1,860. Having dropped the daily cotadutide, AstraZeneca will focus on its weekly GLP-1/glucagon candidate AZD9550.

“We have good clinical data [on cotadutide], but we decided to refocus on the weekly product,” Soriot told Fierce Biotech on the call. “A daily administration is not very convenient for patients, so we decided to focus our efforts on the follow-on compound, which is a weekly administration.” 

Finally, the drugmaker discontinued a phase 1 trial of its anti-GDF15 candidate AZD8853 due to “strategic portfolio prioritization.” AstraZeneca moved the candidate into a phase 1/2 solid tumor trial last year in collaboration with ImaginAb, a biotech that it hooked up with in 2020.