medwireNews: The immunotherapeutic agent interferon-α kinoid (IFN-K) induces neutralizing anti-IFN-α2b antibodies and significantly reduces the IFN gene signature in people with systemic lupus erythematosus (SLE), phase 2b study data show.
And although the clinical coprimary endpoint of a significant improvement in modified BICLA response relative to placebo was not met, Frederic Houssiau (Université Catholique de Louvain, Brussels, Belgium) and co-investigators believe that positive secondary endpoint data show that the treatment merits further investigation in phase 3 studies.
Houssiau et al explain in the Annals of the Rheumatic Diseases that “IFN-K is an immunotherapeutic vaccine composed of inactivated recombinant human IFN-α2b coupled to a T-helper carrier protein (keyhole limpet haemocyanin), aimed at inducing antibodies against IFN-α by active immunisation.”
They tested its efficacy, relative to placebo, in 184 patients (94% women) with moderate to severely active SLE despite standard treatment.
The researchers found that in 91% of the 91 individuals randomly assigned to receive intramuscular IFN-K (240 μg at days 0, 7, and 28, and 120 μg at weeks 12 and 24) neutralizing anti-IFN-α2b antibodies were induced by week 36.
Treatment with IFN-K also induced a 31.3% mean reduction from baseline in the expression of type I IFN-induced genes at week 36, which was significantly greater than the 0.4% reduction observed among the 93 placebo-treated patients, meeting the biologic coprimary endpoint.
By contrast, there was no significant difference between the two groups in the clinical coprimary endpoint of modified BICLA response at week 36, with 41.2% and 34.5% of patients in the IFN-K and placebo groups, respectively, meeting this endpoint.
In spite of this, there were differences between the two groups in secondary clinical outcomes. For example, significantly more patients receiving IFN-K versus placebo attained lupus low disease activity state (LLDAS) at week 36 (52.9 vs 29.8%) and the mean daily prednisone equivalent dose was significantly lower in the IFN-K than in the placebo group from week 28 onwards. By week 36, the mean dose was 5.4 mg/day in the IFN-K group and 7.1 mg/day in the placebo group.
Houssiau and team also report that in exploratory analyses, SRI-4 response rates at week 36 were a significant 17% greater among individuals with neutralizing antibodies and a corticosteroid dose of 7.5 mg prednisone equivalent/day or lower who received IFN-K relative to placebo.
Discussing their findings, the authors point out that it “has been increasingly acknowledged” that failures of type I IFN-targeted agents such as rontalizumab, sifalimumab, and anifrolumab, in phase 3 clinical trials “may be more related to the choice of the outcome measures than to actual inefficacy of the molecules.”
They therefore conclude: “The IFN-K study reported here further fuels this hypothesis, since the drug did not meet its primary endpoint despite a significant steroid-sparing effect and attainment of LLDAS, indicating that the IFN-K deserves further evaluation in phase III studies.”
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