After flunking studies last year, Allakos' failed phase 3 EoDyssey sinks gastrointestinal program

Allakos has achieved an undesired hat trick. Across three phase 3 trials, the biotech has now significantly reduced levels of a troublesome white blood cell without improving symptoms, driving it to rethink the development of an anti-Siglec-8 antibody that was once among the hottest prospects in biotech.

California-based Allakos was flying high going into December’s readouts from late-phase trials of patients featuring three eosinophilic diseases—gastritis, duodenitis and oesophagitis—boasting a market cap north of $4 billion on the strength of one clinical asset called lirentelimab. In both trials, lirentelimab met the histologic co-primary endpoint but failed to improve symptoms, sinking the stock and raising questions about why significantly reducing eosinophil counts had no effect on how patients experienced the disease.

Now, Allakos has confirmed the results were no fluke, reporting top-line data from a third phase 3 trial called EoDyssey that follows the same pattern. This time around, investigators randomized 93 eosinophilic duodenitis patients with moderate-to-severe symptoms to receive lirentelimab or placebo for 24 weeks. Again, recipients of lirentelimab had reduced eosinophil counts but continued to suffer similar levels of symptoms. 

A post-hoc analysis of one of the two studies that failed late last year led Allakos to add a subpopulation to its assessment of EoDyssey. The subpopulation analysis excluded patients with conditions that could confound the symptomatic endpoint, such as active irritable bowel syndrome. However, while Allakos saw numerical symptom improvements in the subpopulation they fell short of statistical significance.

The failure to move the needle in terms of patient-reported symptoms in a third late-phase clinical trial has persuaded Allakos to give up on developing lirentelimab in eosinophilic gastrointestinal diseases, at least for now. The biotech has no plans to run additional trials in the indications, although it has left the door open to doing so in the future. 

Attempts to salvage something from what was once among the most valuable programs in biotech now rest on studies in atopic dermatitis and chronic spontaneous urticaria. Allakos is aiming to report topline data from phase 2 clinical trials in its two remaining target indications in the second half of next year. The biotech ended June with $212.4 million to its name.

Shares in Allakos fell 18% in premarket trading to $3.79, a far cry from when the stock traded above $100 in September 2021.