The Global Head of Neuroimmunology at Genentech discussed the results of a substudy that found that the use of advanced imaging metrics in MS clinical trials may provide specific information about tissue damage and potential repair.
Hideki Garren, MD, PhD
The results of a substudy of a larger, phase 3 trial, OPERA II (NCT01412333), found that in studying 56 subjects with relapsing multiple sclerosis, increases in myelin water fraction were detected in those who started ocrelizumab treatment from the beginning of the study as well as those that switched to ocrelizumab treatment after 24 months of interferon beta-1a (IFN). The researchers point out that the use of advanced imaging metrics in clinical trials may provide specific information about tissue damage and repair.
In the whole brain normal appearing white matter, a decrease was found in the myelin water imaging in subjects treated with IFN from baseline to 6 months (P = .035). In the corpus callosum, the IFN showed a decrease in myelin water fraction during the first 24 months, followed by an increase in myelin water fraction during the next 24 months after switching to ocrelizumab. The ocrelizumab subgroup demonstrated no change in myelin water fraction throughout the 48 months. In the cortical spinal tract, the IFN subgroup showed a decrease between baseline to 24 months but stability after switching to ocrelizumab. There was no change demonstrated in the ocrelizumab subgroup over 48 months.
To further explain the background of this work presented in a poster at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS 2019), NeurologyLive spoke with Hideki Garren, MD, the Global Head of Neuroimmunology at Genentech, in an interview.
Hideki Garren, MD: The results are very exciting. It's an advanced MRI method that was done in a substudy from our OPERA II trial, so this was the phase 3 trial with ocrelizumab in our relapsing MS patients. The substudy done with a collaborator at the University of British Columbia, Anthony Traboulsee, MD. He has advanced MRI technology that he uses to measure a number of different things. This particular technology, which was described in the poster, is a way to measure myelin using the advanced MRI technology called the multi-component driven equilibrium single pulse observation of T1/T2 (mcDESPOT).
What's unique about this is that he had a large substudy, so almost 60 patients. As such, we can benefit because he's able to study these 60 patients using advanced MRI to look at myelin. That's really exciting because, as you no doubt saw in the poster, there's suggestion that ocrelizumab has an effect on myelination—that it may stop the demyelination or it may, in fact, improve some of the myelination. It's early, it’s a small substudy, but the results are exciting in the way the remyelination, of course, is sort of the holy grail of MS development. Because today, of all the drugs we have available for MS, we don't have one that can remyelinate the brain of patients suffering from MS, so we are encouraged by the results that Traboulsee produced here.
I guess it was surprising that there might be some indication that there are patients that are remyelinating. For example, if you look at the poster, what he showed was results from corpus callosum and coracle spinal tract. Corpus callosum is a connection between the 2 hemispheres. If you take the data at face value, there's increased myelin water fraction in patients that received ocrelizumab or patients who switched from interferon beta to ocrelizumab. Again, that's an indication that the myelination is stabilizing or that there's a suggestion that it might even be improving those in this particular measure.
Biomarkers as the whole is a very important focus for Roche and Genentech. This substudy, is just one part of Traboulsee’s analysis, his site has multiple other ways of analyzing the MRI and he'll describe those and future congresses. His substudy, as well as in other parts of the study the overall trial, looks at various biomarkers. Overall within development, whether that be from these phase 3 studies, as well as phase 3b/4 studies, we're looking at a variety of biomarkers and so we're going to continue to share that biomarker data within future congresses.
I think this is an example of an excellent collaboration that we have with our academic collaborators, with Traboulsee and his excellent investigators who have this special technology. We were able to collaborate on producing these results and this collaboration between industry and academia has been very informative for the scientific community and hopefully been beneficial for patients.
Transcript edited for clarity.