Novel cell trafficking inhibitor shows therapeutic potential in RA

Treatment with E6011, a novel cell trafficking inhibitor targeting the fractalkine (FKN)‐CX₃CR1 interaction, confers modest benefits in rheumatoid arthritis (RA), according to the results of a phase II trial.

In total, 190 patients (median age, 56 years; 78.9 percent female) with moderate to severe RA (mean disease duration, 7.1 years) uncontrolled on methotrexate were randomized to receive placebo (n=54) or E6011 at 100 mg (n=28), 200 mg (n=54), or 400/200 mg (n=54).

Treatment was administered subcutaneously at weeks 0, 1, and 2, and then every 2 weeks until week 22. In the E6011 400/200-mg group, patients received 400 mg at weeks 0, 1, 2, 4, 6, 8, and 10 and then 200 mg thereafter.

The trial did not reach its primary endpoint of American College of Rheumatology (ACR)20 response at week 12, with the rates being similar across all treatment groups (37.0 percent with placebo, 39.3 with 100 mg, 48.1 percent with 200 mg, and 46.3 percent with 400/200‐mg).

However, E6011 yielded a significant effect on ACR20 response at week 24, particularly at the 200‐mg and 400/200‐mg doses (53.7 percent and 57.4 percent, respectively; placebo, 35.2 percent; 100 mg, 39.3 percent).

Furthermore, E6011 had a greater effect in the subgroup of patients with higher baseline proportion of CD16⁺ monocytes. Their week-24 ACR20 responses were 30.0 percent with placebo, 46.7 percent with 100 mg, 57.7 percent with 200 mg, and 69.6 percent with 400/200 mg.

E6011 was well tolerated. Treatment-related adverse events (AEs) occurred more frequently in the active treatment groups than in the placebo group (39.7 percent vs 22.2 percent). There was a notable dose-response effect on the incidence of AEs. But the incidences of higher-grade AEs, serious AEs, and discontinuation due to AEs were similar across all groups.

The most common AEs on E6011 were nasopharyngitis, upper respiratory tract infection, stomatitis, bronchitis, back pain, pharyngitis, and dental caries.