Lilly, Nektar Stumble in Phase II Lupus Trial

Lilly_Cristina Arias/Cover/Getty Images

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Rezpegaldesleukin, Lilly’s and Nektar Therapeutics’ candidate for systemic lupus erythematosus (SLE), fell short of its primary efficacy endpoint in the Phase II ISLAND trial, the pharma partners announced Thursday.

Lilly has decided not to advance rezpegaldesleukin in SLE to Phase III consideration. Rezpegaldesleukin remains in development for atopic dermatitis, for which a Phase IIb study is upcoming in an unannounced autoimmune disease.

“The study did not meet its primary endpoint or pre-defined critical success factors,” a Lilly spokesperson told BioSpace via email.

Nektar’s shares dropped 29% in after-hours trading due to the data drop.

In an investor call Thursday, Howard Robin, president and CEO, Nektar said the decision “is based upon their need for the study have reached very high bars” of efficacy in this Phase II study. 

Nevertheless, while rezpegaldesleukin’s run in SLE is over, Robin said the company believes the totality of ISLAND’s data does support pushing through with the candidate’s development, especially considering “contemporary regulatory approvals and the current developments in this field.” 

ISLAND enrolled 291 adults, to whom rezpegaldesleukin was given at three doses once every two weeks: a low dose of 300 mcg, a mid-dose of 900 mcg and a high dose of 1,800 mcg. The study’s primary endpoint was a four-point reduction in scores in the SLEDAI-2K, a clinical tool that assesses SLE disease activity. 

Compared with the placebo, 8.8% of patients treated with the mid-dose rezpegaldesleukin reached the primary efficacy threshold. In a modified intention-to-treat analysis, this effect was not statistically significant, according to the announcement. 

The placebo-adjusted treatment effects of the low and high doses of rezpegaldesleukin were weaker than that of the mid-dose.

Despite missing its primary endpoint, rezpegaldesleukin met most secondary efficacy measures. The mid-dose of the candidate elicited potentially clinically meaningful improvements in other disease scales, such as the Lupus Low Disease Activity State. Biomarker data also showed a dose-dependent increase in T regulatory cells.

“The most important takeaway from this Phase II study is that REZPEG as a single agent clearly showed clinical activity in a difficult-to-treat patient population across many measurements,” Robin said.

As for safety, most adverse events recorded were mild or moderate in severity, though their prevalence grew in a dose-dependent manner. In the high-dose arm, 40% of participants dropped out due to side effects, as opposed to 24% and 19% in the low- and mid-dose groups, respectively.

The most common toxicities that occurred were fever, injection site reaction, fatigue, pain and arthralgia.

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