A key opinion leader highlights the OLKIOS phase 3b study evaluating ofatumumab’s continued efficacy in patients previously treated with traditional anti-CD20 therapy, as well as concerns about switching from a humanized anti-CD20 monoclonal antibody to a fully human monoclonal antibody.
Mark Freedman, MD, MSc: The next study is called the OLIKOS. It was all about whether ofatumumab would maintain efficacy in patients who are coming from traditional anti-CD20 therapies, which are given every 6 months. There was some concern about the continued efficacy of switching from a humanized anti-CD20 monoclonal antibody to a fully human monoclonal antibody. Might there be differences in patients who have maintained benefits? I can’t see why that would be, but one would be concerned about the safety of switching between monoclonal antibodies.
OLIKOS was a 12-month prospective single-arm study because patients are moving from a previous therapy to this one with no comparator. They’re essentially looking at before and after. They had about 100 people who were being randomized through different centers throughout the US. These patients had been previously treated with at least 2 to 5 consecutive courses of either the ocrelizumab or rituximab molecules, both of which target anti-CD20. The last dose was between 4 and 9 months prior to enrollment. They also made sure that these patients were in the relapsing-remitting domain with EDSS [Expanded Disability Status Scale] scores lower than 5.5. They had to show some treatment effect of the previous anti-CD20 in that their B cells had to be substantially below 1%, which are essentially detectable levels in some laboratory tests.
In that sense, they were looking at patients who may have had a suboptimal response to CD20 in the past 6 months. Those patients were also of interest. The so-called suboptimal responders had to have at least 1 relapse, 2 or more Gad [gadolinium]-enhancing lesions or newer enlarging T2 lesions, or had discontinued anti-CD20 therapies because of infusion reactions or recurrent infections. These are the patients that they wanted to do without, so they were excluded for the purposes of seeing continued benefit. The investigators wanted to have no muddy waters here in terms of these patients who may not be responders to begin with.
All the patients were then put onto active therapy. They received the usual dosing. The primary end point was whether there would be a change in MRI at the 12-month mark following enrollment. Then they looked at a number of secondary end points, but didn’t report on everything, such as changes in immune markers, patient satisfaction with the switch, tolerability, and safety. The study design was presented, but we don’t have any results. This is something that’s being generated now, and we’ll have this result perhaps next year at the ECTRIMS [European Committee for Treatment and Research in Multiple Sclerosis] annual congress.
The benefit of such a study would be because, in the real world, there are a lot of people who are taking off-label rituximab. Now that ofatumumab is licensed as a product, maybe they could enroll onto a proper-labeled therapy for relapsing disease and avoid the necessity of coming to infusion centers to have these done. There is a potential, at least for rituximab, which is a humanized monoclonal antibody that is perhaps more associated with infusion reactions, to avoid those completely by moving to a self-administered subcutaneous injection. There are some theoretical and societal advantages of doing your own therapy, rather than having to go to a center, especially in the midst of a pandemic.
The likelihood is that a number of people are going to be making this transition in real life. Being able to show them that making the transition doesn’t affect the continued benefit of the anti-CD20 therapy is obviously a goal of this investigation. The other factor is that there are potential theoretical safety issues of moving from one monoclonal antibody to another in the context of treating MS [multiple sclerosis]. Would this raise any safety issues? One needs to show that that is not the case.