Dr. Peter Chin, a renowned neurologist and Principal Medical Director of Global Neuroscience Development at Genentech, a leading biotechnology company and member of the Roche Group, participated in an exclusive interview with Multiple Sclerosis News Today correspondent Dr. Ana de Barros on the company’s promising multiple sclerosis (MS) therapy ocrelizumab. The new, experimental therapy has made headlines this week after the company presented positive data in the treatment of both Relapsing and Primary Progressive Multiple Sclerosis.
The interview was conducted on Saturday at the end of the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held this year in Barcelona, Spain (October 7 to 10, 2015). Topics that are important to MS patients and the healthcare community were addressed, including adverse side effects, prospects in terms of release and price, and plans for worldwide approval of ocrelizumab. In addition, two questions selected from readers of MS News Today concerning secondary progressive MS and primary progressive MS were addressed.
Listen to full audio of the exclusive interview below:
Roche/Genentech’s experimental MS therapy was discussed several times throughout ECTRIMS 2015, including during Parallel Session 10, entitled “Update on therapies,” where Dr. Stephen Hauser from the University of California, San Francisco presented his work on “Efficacy and safety of ocrelizumab in relapsing multiple sclerosis — results of the interferon-beta-1a-controlled, double-blind, Phase III OPERA I and II studies.”
Ocrelizumab is a recombinant humanized monoclonal antibody against immune B cells that express CD20 proteins at their surface. These cells are thought to be a key contributor to the myelin and neuron damage that leads to motor function impairment, irreversible neurological disability and paralysis in MS patients.
“B cells can contribute to the pathophysiology of MS,” explained Dr. Hauser during his presentation, “targeting CD20-B cells may preserve B cell reconstitution and long-term immune memory.”
Ocrelizumab’s safety and efficacy was assessed in three major Phase 3 clinical trials: OPERA I, OPERA II, and ORATORIO. In his presentation, Dr. Hauser, chair of the Scientific Steering Committee of the OPERA studies, provided data on the trials’ results where ocrelizumab was compared to interferon (IFN)-beta-1a, a well-established MS therapy, in patients with relapsing forms of MS over a treatment period of 96 weeks.
Dr. Hauser showed that ocrelizumab was effective in treating relapsing MS, having a favorable safety profile over 96 weeks. When compared to IFN-beta-1a, ocrelizumab significantly reduced the annualized relapse rate, the 12- and 24-week confirmed disease progression, and existing, new and/or enlarging brain lesions. Furthermore, ocrelizumab also reduced brain volume loss by 23.5% in relapsing MS patients in comparison to IFN-beta-1a therapy, and increased the proportion of patients who did had no evidence of disease activity (NEDA).
“OPERA I and OPERA II showed that targeting CD20-B cells with ocrelizumab is a potential therapeutic approach in relapsing MS,” said Dr. Hauser.
In terms of safety, Dr. Hauser reported that the most adverse events were infusion-related reactions (especially in the first infusions). In the combined cohort of patients who finished the trials (more than 1,000), six malignancies were reported and three deaths occurred, two of them by suicide.
On October 10, a Parallel Session entitled “Late Breaking News” took place at ECTRIMS, with Prof. Xavier Montalban from the Hospital Vall d’Hebron University, Barcelona, Spain, presenting his work under the title “Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis — results of the placebo-controlled, double-blind, Phase III ORATORIO study.”
The ORATORIO trial assessed the efficacy and safety of ocrelizumab in patients with primary progressive MS (PPMS) compared to a placebo. Prof. Montalban showed that 80% of the patients under ocrelizumab treatment completed the study, having achieved its primary endpoint, a significant reduction in 12-week confirmed disability progression compared to the placebo group (by 24%). Furthermore, patients treated with ocrelizumab were found to have a 25% reduction in the risk of confirmed disability progression at 24-weeks, and a significant reduction of 29% in the progression rate of walking time. Ocrelizumab was also found to significantly reduce brain lesions by 3.4% in comparison to a placebo therapy, and to promote a reduction in whole brain volume loss by 17.5% (week 24 to week 120).
In terms of safety, Prof. Montalban reported, “Throughout the mean treatment duration of approximately 3 years, ocrelizumab showed a favorable safety profile; overall, the proportion of patients experiencing adverse events and serious adverse events associated with ocrelizumab, including serious infections, was similar to placebo”. Five deaths were reported, one in the placebo group and four on the ocrelizumab group, linked to conditions like pneumonia, pulmonary embolism and pancreas carcinoma. Complete safety analysis is currently underway, including investigation of any malignancies.
Prof. Montalban concluded, “ORATORIO data show that B cells may play a role in PPMS pathophysiology,” and that ocrelizumab significantly reduced the confirmed disability progression and brain volume loss in PPMS patients.
Ocrelizumab is now considered the first investigational drug to significantly reduce disability progression in patients with relapsing MS and PPMS. This is especially important for patients with PPMS as there are no approved treatments for this form of the disease.