Lilly’s Missteps Revealed: Rezpeg Atopic Dermatitis Trials Show Flawed Miscalculations

Nektar Therapeutics made an unexpected announcement on Monday – its investigational regulatory T-cell stimulator rezpegaldesleukin (rezpeg) has not been delivering the efficacy data as expected. The potential treatment for atopic dermatitis was part of a joint development programme with pharmaceutical giant Eli Lilly, who unfortunately miscalculated the data.

At the 31st Congress of the European Academy of Dermatology and Venereology (EADV), held in September 2022, Lilly presented promising data from a Phase Ib study on rezpeg. Patients experienced positive and dose-dependent improvements in key efficacy measures, but unfortunately these effects did not quite reach the required statistical significance.

At 12 weeks, Lilly’s incorrect results reported a 53% and 66% improvement in Eczema Area and Severity Index (EASI) scores with the 12-µg/kg and 24-µg/kg doses of rezpeg, respectively, compared to the 49% improvement due to placebo relative to baseline. Sadly, Nektar states that neither dose was significantly different than placebo.

Nektar’s re-analysis revealed that patients who received the highest dose of Rezpeg showed an incredible 83% improvement in their EASI scores after 12 weeks, significantly better than the placebo with a p-value of 0.002. The corrected data also showed that an impressive amount of patients achieved a 75% reduction in EASI scores from their baseline.

Nektar’s insightful analysis shows that rezpeg, a unique and distinct form of T regulatory cell therapy, has the potential to revolutionize the treatment of atopic dermatitis, according to CEO Howard Robin. Its impressive efficacy is likely to significantly benefit patients suffering from this chronic condition.

Harnessing the body’s natural defence against inflammation and autoimmune disorders, Rezpeg is an innovative molecule that targets the IL-2 receptor complex to selectively boost the production of regulatory T-cells. By promoting a balanced immune system, Rezpeg could pave the way for life-changing treatments for people suffering from these kinds of disorders.

In July 2017, Lilly and Nektar excitedly announced their strategic collaboration, linking their hopes and dreams to co-develop rezpeg. However, unforeseen circumstances came to pass on April 2023, when the miscalculated data presented at the EADV 2022 sparked a chain of events that caused Lilly to withdraw from the alliance and reclaim all rights to rezpeg from Nektar.

By regaining control of the rezpeg program, California’s biotech firm seized a golden opportunity. They accessed raw data files from the Phase Ib study, and eagerly reviewed them before handing them off to an independent statistical firm for validation. There was a sense of excitement as the team awaited the official results, in what could turn out to be a groundbreaking venture.

Re-analysis by Nektar revealed miscalculations by Lilly regarding a Phase Ib study with corrections showing a powerful treatment effect of rezpeg on the Psoriasis Area and Severity Index score. Promptly, Nektar informed Lilly’s internal statistical and clinical teams of the errors, which the pharma giant then confirmed via written communications.

In February 2023, Lilly and Nektar’s pipeline hit a roadblock when rezpeg failed the Phase II ISLAND trial, unable to demonstrate efficacy in Systemic Lupus Erythematosus. This result caused Lilly to abandon their Phase III plans in this indication, forcing them to return rezpeg back to Nektar.

Nektar is poised to begin a new Phase IIb study of repzeg in October 2023, for biologic-naïve patients with moderate-to-severe atopic dermatitis who have responded poorly to topical corticosteroid treatment. The study promises exciting developments for these individuals and promises to provide new treatments and approaches to managing atopic dermatitis.

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