Primary Results From the ENSEMBLE PLUS Study
Xavier Montalban, MD, PhD: I would like to discuss the ENSEMBLE PLUS study, which is a study on the short infusion time of ocrelizumab. As you know, ocrelizumab is an anti-CD20 monoclonal antibody, which has been approved in the United States and also in Europe and in the rest of the world, for the treatment of relapsing-remitting MS [multiple sclerosis] and also for primary progressive MS. In fact, it is the only drug approved for the treatment of primary progressive MS.
Typically the infusion duration is about 6 hours in total, which is OK in the sense that it’s a convenient drug; you take that drug IV [intravenously] every 6 months. Six hours is OK, but we would like, of course, to have a shorter infusion period. ENSEMBLE PLUS was a randomized, double-blinded substudy to the single-arm ENSEMBLE study. And if you remember, ENSEMBLE was a trial on early relapsing-remitting MS, naive patients with a disease duration of less than 3 years. In ENSEMBLE PLUS, ocrelizumab, the usual dose of 600 mg was administered over the approved infusion time, which is about 3 to 3.5 hours, and was compared to a shorter infusion period of about 2 hours.
And at the end, 291 patients and 289 patients were randomized to the conventional and shorter infusion subgroups, respectively. And in fact, we didn’t find big differences at all. In the first randomized infusion, 23% in the conventional, and 24.6% in the shorter infusion group, had some sort of infusion reactions. And most of the infusion reactions were mild to moderate, which is good news. Most of the infusion reactions resulted without any problem at all.
No infusion reactions in either of the 2 groups were life-threatening, serious or fatal, and we had 1 severe infusion reaction in each of the groups. One in the conventional and the other in the shorter-duration group. So no infusion reaction—related discontinuations occurred, which is also very good news.
I think the conclusion here is that this primary analysis suggests that the frequency and severity of infusion reactions are comparable between the conventional and shorter infusions, and no new safety signals were detected. And I think this is important. Specifically in the era we are living in now, this COVID-19 [coronavirus disease 2019] era, where we don’t want patients to spend too much time in infusion centers or in the hospital. So the shorter period for the infusion is better for the patient and for the hospital as well. I think from the scientific point of view it’s not an extraordinary trial. But from the practical point of view, I think it’s a very good piece of information.