Following on from the success of it's previous ENIGMA study, Biotechnology company Allakos has announced results from its ENIGMA 2 and KRYPTOS studies of lirentelimab in the treatment of eosinophil and mast-related diseases.

Both studies met the histologic endpoints in reducing the eosinophil count but disappointingly did not reach their symptomatic endpoints.

As a charity, we acknowledge the challenge of symptoms and histology not always correlating and how it continues to make these diseases difficult to manage and treat, as demonstrated by these trials.

ENIGMA 2

Study

ENIGMA 2 was a Phase 3 24-week randomised double-blind placebo-controlled study of lirentelimab patients with eosinophilic gastritis (EG) or eosinophilic duodenitis (EoD). The co-primary endpoints were:

1. The proportion of patients achieving histologic resolution (defined as ≤4 eosinophils (eos) / high powered field (hpf) in 5 hpfs in the stomach and/or ≤15 eos/hpf in 3 hpfs in the duodenum)
2. Symptomatic improvement as measured by absolute change in the patient-reported six symptom total symptom score (TSS)

Results

In the lirentelimab group (n=91), 84.6% of patients achieved histologic resolution (p<0.0001) vs 4.5% in the placebo group (n=89). In the lirentelimab group, absolute mean change in the TSS was -10 (p.0343) vs -11.5 in the placebo group.

No new safety signals were observed.

KRYPTOS

Study

KRYPTOS was a Phase 2/3 24-week randomised double-blind placebo-controlled study of lirentelimab in patients with eosinophilic oesophagitis (EoE). The co-primary endpoints were:

1. The proportion of patients achieving histologic resolution (defined as ≤6 eosinophils (eos) / high powered field (hpf) in the oesophagus)
2. Symptomatic improvement as measured by absolute change in dysphagia symptom questionnaire (DSQ)

Results

In the high-dose lirentelimab group (n=91), 87.9% of patients achieved histologic resolution (p<0.0001) vs 92.5% (p,0.0001) in the low-dose group (n=93) and 10.9% in the placebo group (n=92).

Absolute mean change in the DSQ score was -17.4 (p=0.237) in the high-dose group vs -11.9 (p=0.247) in the low-dose group and -14.6 in the placebo group.

No new safety signals were observed.

Looking ahead

Although the EGID results are surprising and disappointing, we will continue to analyze the data to understand the results and to determine the path forward for lirentelimab in EGIDs. At present we intend to continue our development efforts with subcutaneous lirentelimab in atopic dermatitis, chronic spontaneous urticaria, and asthma. The atopic dermatitis study is underway and we plan to initiate chronic spontaneous urticaria and asthma studies in 2022 and will continue to advance other programs in our preclinical pipeline.

- Dr. Craig Paterson, MD
Chief Medical Officer of Allakos

Links

• Allakos' Press Release on ENIGMA 2 and KRYPTOS studies
• ENIGMA Phase 2 study results
• Allakos announces Lirentelimab development into Atopic Dermatitis, Chronic Spontaneous Urticaria and Asthma