Results from a Phase IIb study involving epratuzumab, a new humanised IgG1 monoclonal antibody in development by UCB and Immunomedics for systemic lupus erythematosus, have impressed investigators.
Data from the 12-week EMBLEM study were presented at the American College of Rheumatology meeting in Atlanta by lead investigator Daniel Wallace of Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles. “This was primarily a dose-ranging study comparing five doses and dose schedules between 200mg and 3600mg against placebo,” he told rheumatologists who crowded into an oral session to hear the data. But the study also suggested promising information on safety and efficacy from the 227 patients with active moderate and severe SLE who took part, he added.
All cumulative doses were superior to placebo, he said. “However, patients who received a cumulative dose of 2400mg either by 600mg weekly or 1200mg every other week saw a clear, clinically meaningful and statistically significant improvement in their condition by 12 weeks compared to placebo.” Response rates observed for epratuzumab were more than double those for placebo. Improvement was measured by BILAG-2004 (British Isles Lupus Assessment Group) criteria and by SLEDAI (SLE Disease Activity Index) scores.
By week 12, significantly more patients receiving epratuzumab 600mg weekly had improved their baseline BILAG A/B scores to BILAG D in all six body systems (indicating no active disease) than patients receiving placebo.
Epratuzumab, which targets CD22, also reduces B cells but only by a modest amount, said Dr Wallace. Benefit started to be apparent quickly, within four to eight weeks. This is faster-acting than drugs with a larger B-cell depleting effect, he commented.
“The degree of improvement was substantial. These were sick patients and I’m very excited about the results we saw from epratuzumab.” Most patients had high disease activity at baseline, he noted., and over 70% had more than one BILAG A score across multiple organ systems.
Adverse events including infections and injection site reactions, and serious adverse events were similar in both the treatment and placebo arms of the study. “The drug was very well tolerated and there were no new safety signals,” he added
Co-investigator Ken Kalunion of the UCSD School of Medicine, La Jolla, said: “These are small numbers but the results are very encouraging. It’s hard to say from a Phase II trial but this drug could prove to be a breakthrough in SLE”. He added: “The most dramatic improvements seen were in the cardiorespiratory and neuropsychiatric organ systems.” In the former, all patients receiving the 600mg dose improved to BILAG D by 12 weeks. And in the neuropsychiatric system, 5 out of 6 patients in the 600mg weekly group went from BILAG B to D.
Another co-investigator, Vibeke Strand of Stanford University, Palo Alto, commented: “It is terrific to see improvement within three months that is clinically meaningful. I am very excited about epratuzumab. I think it’s a great drug that may have potential to be an induction therapy. I’m eager to see where it goes in Phase III.” Trials are expected to begin early 2011, Dr Wallace said.
SLE affects about 50 per 100,000 people in the USA and the conditionis currently regarded as having an unmet clinical need. Although thereare several symptomatic treatments there are none that tackle theunderlying pathology of SLE.