Nektar Therapeutics is enjoying the sweet taste of clinical trial success after years of swallowing bitter pills. The biotech reported a phase 2 win for rezpegaldesleukin in atopic dermatitis, sending its stock up 119% despite the data falling short of the bar set by Regeneron and Sanofi’s major blockbuster immunology drug Dupixent.
Rezpeg, as it is also known, is an IL-pathway agonist and regulatory T-cell (Treg) proliferator. While most atopic dermatitis treatments work by blocking immune activation, rezpeg is designed to stimulate Treg cells the body makes to dampen inflammatory reactions. The idea is to rebalance the immune system to provide lasting relief from the symptoms of atopic dermatitis and other autoimmune and inflammatory diseases.
Nektar tested the idea in a phase 2b trial that randomized 393 patients with moderate to severe atopic dermatitis to receive one of three doses of rezpeg or placebo. After 16 weeks, Nektar reported a 61% improvement in symptoms on the high dose and a 31% improvement on placebo, achieving its primary endpoint. The two lower doses also performed significantly better than placebo.
Symptoms improved by at least 75% on the EASI score in up to 46% of patients taking rezpeg. The middle dose performed numerically better than the high dose on EASI-75 and an investigator scale. Otherwise, the data showed dose-dependent trends, with EASI-90 topping out at 25% on the high dose.
The high dose performed significantly better than placebo against all the endpoints Nektar looked at in its top-line data analysis. But the high level of competition for the atopic dermatitis market means rezpeg will face tougher comparisons than placebo. EASI-75 and EASI-90 for Dupixent were 52% and 30%, respectively, in a phase 2b trial.
Cytokine-, microbiome- and toleragenic-based approaches to restoring immune homeostasis are more directly comparable to rezpeg. OX40 candidates such as Sanofi’s amlitelimab are potential rivals, but Nektar believes it has a differentiated candidate.
“We saw a rapid onset of response for all three endpoints and especially for EASI-75 and itch, separating from placebo quickly within a few doses of receiving rezpeg,” Nektar CEO Howard Robin said on a call with analysts to discuss the data. “This is a key differentiator from other immune-modulation approaches such as OX40 pathway inhibitors.”
Jonathan Zalevsky, Ph.D., chief research and development officer at Nektar, told analysts cross-trial comparisons with OX40 studies are instructive because the trials “were completed in similar time frames, had similar global footprints and had similar statistical designs.” The biotech is now preparing for phase 3.
“This study really gives us everything that we need to design the phase 3 regimen,” Zalevsky said. “I am very confident we're in great shape to have just one dose level and regimen for the phase three 3.”
The data sent Nektar’s share price up 119% to $20.90 in premarket trading. Nektar has endured tough years since its big-ticket Bristol Myers Squibb oncology collaboration collapsed in the face of weak data. Eli Lilly was partnered on rezpeg but exited after a clinical setback. Nektar then accused Lilly of a botched analysis that understated the effect of the drug candidate.
Nektar emerged with full rights to rezpeg, but, with the stock trading below cash, investor hopes were low going into the phase 2b readout. The top-line data prompted a reevaluation of Nektar’s prospects.