An Update on Ocrelizumab: Part 2
Laura Kolaczkowski and I had the opportunity to speak to Dr. Peter Chin, the Principal Medical Director for Genentech-Roche, to discuss the significance of the study results and obtaining breakthrough designation. In Part 1 of our interview we reviewed some of the background of ocrelizumab, and discussed the significance of getting breakthrough designation from the FDA. In Part 2 we are going to speak to Dr. Chin about why ocrelizumab is such a ground breaking therapy, and the results of the clinical trials.
Q: Can you tell us more the results from the ORATORIO study, which compared ocrelizumab to placebo in people with progressive MS?
Dr. Chin: Yes, this is the first positive phase III trial in progressive MS which in of itself was an important milestone. In general it is difficult to do studies on people with progressive MS, and trials take a lot of time. We have to wait years to see what PPMS looks like, and how it progresses. This is different than trials for relapsing MS because the main measurement of treatment success or failure is the rate of relapses, which tend to happen frequently in comparison. The main focus of the ORATORIO study was to see if ocrelizumab slowed disability accumulation in progressive MS. We measured this by doing frequent neurological exams, and disease progression was defined as an increase in their EDSS score that was sustained for at least 12 weeks. In other words, if there was a worsening of disability for at least 3 months then we were confident that the participants MS had progressed.
Ocrelizumab was associated with a significant reduction (24%) in 12 week confirmed disability progression over course of the treatment period. Furthermore, 24 week confirmed disability progression (which is a more robust measure of disease accumulation) was also significantly reduced. There was also a significant reduction in the rate of change of the timed 25 foot walk (a frequently used measurement of MS disease progression). During trials the T2 lesion volume (accumulation of demyelinating lesions over time) increased by 7.4% in the placebo group, and actually decreased by 3.4% in the ocrelizumab group which was highly significant. There was also a significant difference in the rate of brain volume change from week 24 to week 120 between the two groups.
Q: Were there any cases of PML reported during clinical trials?
Dr. Chin: Right now I can only talk about the data that has been publicly presented. There were no cases of PML in either treatment group in the OPERA studies (which compared interferons to ocrelizumab for relapsing MS) or in the ORATORIO study. Ocrelizumab has also been studied as a potential treatment for lupus and rheumatoid arthritis, and there were no cases of PML in those clinical trials either.
Q: What other safety data can you speak to?
Dr. Chin: From OPERA I and II the overall proportion of adverse events from the interferon and ocrelizumab group were very similar. More serious adverse events were reported in 8.7% of the interferon group and 6.9% of the ocrelizumab group. Specifically, serious infections occurred in 2.9% of the interferon group and 1.3% of the ocrelizumab group. The progressive MS trial was similar, the rate of adverse events was very similar between the placebo and treatment group and more serious events were reported in 22.2% of placebo group, and 20.4% of the ocrelizumab group.
Q: Was there a subset of patients that seemed to benefit the most from ocrelizumab?
Dr. Chin: It is a little too early to speculate on that at this time. The FDA is going to determine the labeling of ocrelizumab based on our data, and we are still actively analyzing the data from all of the trials. Our studies included people with a diagnosis of PPMS who did not have a history of relapses and who were ages 18-55 with an EDSS between 3 and 6.5. There did appear to be equal efficacy among people with and without active inflammation at baseline, which may help to identify a more specific subset of patients who will benefit from ocrelizumab in the future.
Q: If approved, do you think everyone with PPRMS should be offered ocrelizumab as a treatment option? Why or why not?
Dr. Chin: That is a question best left to the clinician and the patient after having a conversation about benefit and risk. We will publish the data and health authorities will review it, but it is difficult for us to speculate who should receive this treatment or how it should be used at this time. We are still analyzing the study data, and over time we will learn more about the safety and efficacy of ocrelizumab. As of now we are very encouraged by what we have found, and it is an exciting development. There is clearly an unmet need in PPMS, and even though we already have therapies for RRMS there is also an unmet need for a portion of that population as well. However, as with all therapies only the patient and their provider can decide if ocrelizumab is right for them.
At this point it is still too early to say whether ocrelizumab will ultimately be approved by the FDA, and when it may become available as a treatment. More news will be released in the upcoming months once the FDA application is submitted, and as more data from the trials is analyzed by researchers and regulatory agencies. We will be sure to keep up you up-to-date!