Despite falling short of its primary Phase II objective, Nektar plans to push its T cell stimulator rezpeg into Phase III development.
Nektar Therapeutics’ investigational IL-2 agonist rezpegaldesleukin was unable to significantly ease disease severity in a mid-stage study of patients with alopecia areata.
The Phase II failure seems not to have deterred the California-based company, however, which in its Tuesday news release insisted that rezpegaldesleukin, or rezpeg, achieved its “target product profile” and said the asset will move forward to late-stage development next year.
Nektar’s confidence appears to come from what it claims are enrollment issues, which in turn led to rezpeg’s miss. Specifically, the biotech said that four patients were enrolled in the Phase IIb REZOLVE-AA study despite having “major study eligibility violations that should have disqualified them.” Nektar did not specify what these disqualifying issues were.
Still, the company noted that removing these patients from the analysis would result in the trial’s success.
In a note to investors on Tuesday, analysts at William Blair were also bullish on rezpeg’s potential in this indication. “We believe rezpegaldesleukin exhibits clinical activity in alopecia areata, despite missing statistical significance on the primary endpoint,” they wrote, likewise alluding to potential improvements in efficacy over the long term.
“Since there is not a noticeable plateau, it is conceivable that the proportion of patients achieving less than 20% hair loss could increase with longer follow-up,” the analysts continued.
Shares of Nektar dipped 7% to $49.16 at market close Tuesday.
In the overall analysis, REZOLVE-AA found that a 24-µg/kg dose of rezpeg treatment decreased mean scores on the Severity of Alopecia Tool (SALT) by 28.2% at 36 weeks, while an 18-µg/kg dose led to a 30.3% drop. Placebo comparators, on the other hand, saw an 11.2% reduction in SALT scores over the same time period. The treatment effects of both dose strengths were not statistically significant.
Excluding the four problematic patients, however, was enough to push rezpeg past the statistical bar. The higher- and lower-dose arms saw a 29.6% and 30.4% SALT drop, respectively, while placebo scores decreased by 5.7%. P-values for the respective rezpeg arms were 0.049 and 0.042.
Still, the William Blair analysts conceded that “rezpeg’s efficacy is not competitive with low-dose JAK inhibitors.” Even when excluding the four patients with problematic enrollment, the placebo-corrected percentage of participants achieving SALT scores below 20 ranged from 8.1% to 8.9%, the firm explained, which “is lower than management’s expectations of about 15%.”
Nektar plans to present full REZOLVE-AA findings at a medical conference next year, while data from the ongoing 16-week extension phase will come in during the second quarter of 2026.
