MEDI2070 shows clinical benefit in Crohn's previous treatment failures

WASHINGTON — A novel monoclonal antibody was associated with improved outcomes in a cohort of patients with active Crohn’s disease, according to findings presented here.

Bruce E. Sands, MD, of the Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, New York, and colleagues investigated of MEDI2070 (MedImmune), a human IgG2 monoclonal antibody that targets IL-23 by selectively binding to its p19 subunit, in a cohort of 121 patients with active Crohn’s disease.

Bruce E. Sands

Eligible participants were adults with a Crohn’s Disease Activity Index (CDAI) score of 220 or greater and 450 or less, active inflammation, and who had failed or were intolerant to anti-TNF therapy.

“This was a fairly ill population with a mean CDAI score above 300,” Sands said.

The majority of patients had prior exposure to inflixumab and adalimumab.

Protocols of the double-blind trial called for patients to be assigned MEDI2070 700 mg IV or placebo at weeks 0 and 4 and then followed through week 12. Patients were stratified by the number of anti-TNF agents they had previously taken (1 vs. >1). The intention-to-treat population included 59 patients in the active drug group and 60 patients on placebo.

“This was a simple study design,” Sands said.

The primary endpoint was the proportion of patients who received at least one dose of the study drug who responded clinically, which was defined as a decrease of 100 points or more from baseline CDAI score or clinical remission (CDAI <150) at week 8. “One or the other of these things was defined as clinical effect,” Sands said.

Patients were followed for 12 weeks for safety outcomes.

Clinical effect was reached by 49.2% of patients in the study drug group and 26.7% of those in the placebo group, for a significant difference of 22.5% (P = .010).

Week 8 clinical remission occurred in 27.1% of patients in the MEDI2070 group and 15% of those receiving placebo, a non-significant difference of 12.2%. Also at week 8, clinical response was reported in 45.8% of active therapy patients and 25.0% of those on placebo (P = .017).

The researchers also calculated a composite endpoint of clinical effect and a reduction of 50% or more from baseline in fecal calprotectin or C-reactive protein. The study drug yielded a 42.4% rate of this outcome, compared with 10% for placebo. The difference was 32.4% (P < .001).

About two-thirds of patients experienced treatment emergent adverse events. “Importantly, there were no differences in infections or infestations that resulted in discontinuation,” Sands said.

Overall, adverse event rates at 12 weeks were similar between the two groups.

“MEDI2070 demonstrated a clinical effect at 8 weeks in patients with active [Crohn’s disease] who have failed anti-TNF therapy,” he concluded. – by Rob Volansky

For more information:

Sands BE, et al. Abstract 830. Presented at: Digestive Disease Week, May 16-19, 2015; Washington, D.C.

Disclosure: Sands reports being a consultant and receiving research grants from MedImmune, and that the study was co-sponsored by MedImmune and Amgen. Please see the DDW faculty disclosure index for all other researchers’ relevant financial disclosures.