The global head of neuroimmunology at Genentech spoke about the wealth of data being presented on its anti-CD20 monoclonal antibody ocrelizumab, as well as the success thus far in trials of its NMOSD agent, satralizumab.
Hideki Garren, MD, global head of neuroimmunology, Genentech
Hideki Garren, MD
A number of presentations at ECTRIMS 2019, September 11-13 in Stockholm, Sweden, focus on the impact of long-term treatment with ocrelizumab (Ocrevus, Genentech) in multiple sclerosis (MS). Approved for the treatment of both relapsing and primary progressive disease, the therapy has been an important addition to the MS armamentarium for the last few years.
This year, 6- and 10-year data are being presented, as well as a number of additional analyses of pivotal trial data, some of which has provided new insights into the benefits that the humanized anti-CD20 monoclonal antibody may provide for disability and disease progression. As well, a number of datasets for another Genentech agent, satralizumab, in the treatment of neuromyelitis optica spectrum disorder (NMOSD) were also presented.
To find out more about the wealth of information being presented at the meeting, NeurologyLive spoke with Hideki Garren, MD, global head of neuroimmunology, Genentech, about the data and what it may mean for physicians in the field treating these conditions.
Hideki Garren, MD: So, CASTING is one piece of that data, but we also have our pivotal studies that show that early treatment with Ocrevus is beneficial to patients. To go back to that pivotal data, we have data here over 6 years of treatment that shows that with continuous Ocrevus treatment, we have a lower disability progression compared to patients who switched to Ocrevus treatment—and this is in both arms of the study, as well as in the primary progressive MS study. If you remember, we had 2 relapsing MS studies in phase 3 and 1 primary progressive MS study in phase 3 and both studies show that the earlier you treat, the better your long-term outcome is.1
What's really exciting is, in our primary progressive study, we have another presentation at ECTRIMS 2019 that shows that we actually reduced the time to wheelchair for these patients in their studies. The EDDSS score is a measure of disability, and when EDSS hits 7 that means patients are in a wheelchair. Our analysis showed that with earlier Ocrevus treatment, we delayed patients getting to EDSS 7 and it's great quite exciting.
With CASTING—because that is an early intervention study—we show that patients have an 87% reduction in NEDA progression, so all 3 studies show the same thing, that early treatment is beneficial to patients.
Again, it showed that 87% had a reduction in the evidence of disease activity after switching to Ocrevus. The study was done in patients that had a suboptimal response, that were not responding to prior treatment, and we showed that by switching to Ocrevus, that they have this significant reduction in the number of patients with evidence of disease activity after 1 year. Also, in that study, by the way, patients showed greater satisfaction with Ocrevus compared to prior DMTs.2
With Ocrevus, there is data for a biomarker called NfL—neurofilament light chain—which is very, very exciting because the data we find here is unique in that it took NfL from blood. Blood was taken from patients in our phase 3 studies, and there we show that if you measure NfL at baseline, it correlates with long-term disability in these patients. Furthermore, if you follow NfL with Ocrevus treatment, it significantly reduced the amount of NfL in the blood of these patients. NfL is a marker of neuron cell destruction, so this potentially is a biomarker of disability progression in these patients. And again, Ocrevus reduces that in our pivotal studies, so it’s very, very exciting.3
The other molecule, satralizumab, which is an anti-IL-6 receptor, is being developed for NMOSD. Here we’re showing the second of 2 phase 3 studies. The first phase 3 study, the add-on study, we presented last year at ECTRIMS. This year, we’re showing for the first time, our monotherapy data from our phase 3 study. With these 2 phase 3 studies together, we’re trying to get satralizumab to patients as soon as possible for NMOSD.4
This is very exciting because up until this year, NMO patients had no approved treatments available. There’s now 1 approved treatment, and we’re hoping to have satralizumab available to patients very soon.
We believe that satralizumab could be available for a broad spectrum of patients with NMOSD. Our studies were done with it as monotherapy and as add-on therapy, and in both studies, we have both positive and negative AQP4, or aquaporin-4, antibodies—a biomarker that’s used to diagnose patients with NMOSD. We had both positive and negative patients in our studies, so again, a broad spectrum of patients. Furthermore, we not only have adults, but we have adolescents in our studies. Therefore, we believe that satralizumab should be available for a broad spectrum of patients with NMOSD, including those who are APQ4 positive and negative, adults and adolescents, as both monotherapy and add-on.
For satralizumab, again both studies were positive, both hit the primary end point, and one was add-on and one was monotherapy, so that’s obviously very positive for us and very exciting. For Ocrevus, we have now treated 120,000 patients worldwide, so Ocrevus is being given to a large number of patients. In the US, it is the number 1 drug for new treatments as well as patients who have switched treatments, so that’s very exciting as well. Those two pieces of information about satralizumab and Ocrevus were just really exciting news.
Both of them represent our commitment to neuroscience, and obviously our commitment to MS and NMOSD, but Roche and Genentech are committed to neuroscience. We have programs in Alzheimer disease, in spinal muscular atrophy, in neuromuscular diseases, and it really represents what we want to do for the highest unmet medical need patients. We want to try to preserve patients and slow their disease progression, and maybe one day to reverse progression as patients get worse.
Transcript edited for clarity. For more coverage of ECTRIMS 2019, click here.
1. Giovannoni G, Kappos L, Hauser SL, et al. Long-term reduction of relapse rate and confirmed disability progression after 6 years of ocrelizumab treatment in patients with relapsing multiple sclerosis. Presented at: ECTRIMS 2019. September 11-13, 2019; Stockholm, Sweden. Abstract P1015.
2. Vermersch P, Erälinna JP, Nicholas R, et al. Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis with a suboptimal response to previous disease-modifying therapies (1-year interim results). Presented at: ECTRIMS 2019. September 11-13, 2019; Stockholm, Sweden. Abstract P690.
3. Bar-Or A, Thanei GA, Harp CT, et al. Blood neurofilament light levels are lowered to a healthy donor range in patients with RMS and PPMS following ocrelizumab treatment. Presented at: ECTRIMS; September 11—13, 2019; Stockholm, Sweden. Abstract 152.
4. Traboulsee A, Greenberg B, Bennett JL, et al. Efficacy and safety of satralizumab monotherapy for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD): results from SAkuraStar, a double-blind placebo-controlled Phase 3 clinical study. Presented at: ECTRIMS 2019. September 11-13, 2019; Stockholm, Sweden. Abstract P603.