Long-Term Ocrelizumab, Satralizumab Data Offer Insights into MS and NMOSD Care

Ashish Pradhan, MD

At the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), October 13-15, several presentations offered new insights into the clinical use of ocrelizumab (Ocrevus; Genentech) in the treatment of patients with multiple sclerosis (MS), as well as satralizumab (Enspryng; Genentech) as a therapy for those with neuromyelitis optica spectrum disorder (NMOSD).

These presentations provided updates for the clinical community on the long-term use of ocrelizumab in its approved patient population—those with relapsing and primary progressive disease—and how those treated with it have fared in the time of COVID-19. Data on satralizumab offered a long-term look at the relatively new therapy for NMOSD.

To find out more about this collection of data presented at ECTRIMS and what the clinical community should know, NeurologLive inquired with Ashish Pradhan, MD, executive director and disease area lead for MS and NMOSD, Genentech.

NeurologyLive: How vital has it been to continue to collect these various new data sets on ocrelizumab since its approval?

Ashish Pradhan, MD: Following the Ocrevus FDA approval in 2017, and with more than 200,000 people treated globally in clinical trial and real-world settings, we continue our commitment to advancing the science and initiating innovative clinical research programs to broaden the scientific understanding of MS and improve the way it is treated with the ultimate goal of stopping disease progression for people living with MS. New Ocrevus data presented at ECTRIMS 2021 are a testament to our continued commitment to making meaningful scientific progress for people living with MS.

New long-term data show early and ongoing treatment of Ocrevus significantly reduced risk of disability progression in relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS), and data from all Ocrevus clinical trials also show a favorable benefit-risk profile over eight years.

These data from the OPERA and ORATORIO open-label extension (OLE) studies further reinforce the potential benefit of treating people with MS earlier in the course of their disease to delay disability progression and help reduce the impact of the disease on the daily lives of patients and their families.

New safety data representing 5688 patients with RMS and PPMS and 21,675 patient-years of exposure to Ocrevus, across all Ocrevus clinical trials further demonstrate the consistently favorable benefit-risk profile of Ocrevus over 8 years.

What have the shorter-infusion studies shown in their subgroup analyses?

When treated with a shorter, 2-hour Ocrevus infusion, the rate and severity of infusion-related reactions (IRRs) in Black/African-American and Hispanic/Latino populations were similar to those reported in the overall patient population in a subgroup analysis of three studies.

The analysis examined results from shorter infusions in 3 studies: SaROD (dose 2 or 3), CHORDS (dose 5), and ENSEMBLE PLUS (dose 2-6).

Demographics and baseline characteristics were comparable to the overall study populations, except for slightly longer disease duration in Hispanic/Latino patients and slightly shorter disease duration in Black/African-American patients in the CHORDS and ENSEMBLE PLUS groups.

Rates of IRRs in Black/African-American and Hispanic/Latino patients were similar to the overall population:

• SaROD: 12.5% and 25%, respectively, vs 48.4%
• CHORDS: 8.3% and 16.7%, respectively, vs 12.4%
• ENSEMBLE PLUS: 20% and 29.4%, respectively, vs 28.6%

No serious or grade 3 or higher IRRs were observed in Black/African American or Hispanic/Latino patients.These patient populations may experience greater disease severity and faster progression yet are vastly underrepresented in most clinical trials. A shorter infusion time may help reduce the burden on these patient populations and increase their access to treatment.

What do clinicians need to know about what’s been observed thus far with ocrelizumab in the time of COVID-19?

Patient safety is Genentech’s highest priority, and we are closely monitoring the evolving situation to best understand how the vaccine will impact people with MS and people who are treated with Ocrevus. We are committed to characterizing the natural immune response to SARS-CoV-2 in people treated with Ocrevus and are undertaking a number of initiatives both internally at Genentech and externally in collaboration with the MS community. Data from our research partners in Italy presented at ECTRIMS 2021 show:

• Patients treated with Ocrevus had similar T cell responses to healthy controls after natural infection.
• Virus-specific T cell memory stem cells and responses were detected as long as one year after infection in Ocrevus-treated patients.

We are also studying immunization response in Ocrevus-treated patients vaccinated with authorized SARS-CoV-2 vaccines. Data from our research partners at New York University presented at ECTRIMS 2021 show:

• Patients treated with Ocrevus had similar T cell responses to non-treated MS controls after vaccination.
• Antibody responses to vaccination were attenuated in patients treated with Ocrevus, but T cell responses were observed regardless of a person’s antibody response.

We have already studied response to vaccinations against common pathogens/viruses, including influenza, in Ocrevus-treated patients with MS and patients were able to mount an antibody immune response, albeit attenuated.

The twice-yearly (6-monthly) scheduled dosing interval for Ocrevus should provide the time window needed to apply the currently available COVID-19 vaccines and boosters.

For you, is there a presentation at ECTRIMS that stands out as particularly important for the clinical community to know more about ocrelizumab?

New, key long-term data show earlier treatment with Ocrevus continues to impact disability progression up to 7.5 years in people with RMS and 8 years in people with PPMS in the phase 3 OPERA and ORATORIO OLE studies.

Findings showed a 35% reduction in risk of needing a walking aid in RMS after 7.5 years vs. initiation 2 years later in Phase III OLE and a 29% reduction in 48-week confirmed disability progression in PPMS after 8 years vs initiation after double-blind period in phase 3 OLE. These new long-term data reinforce the benefit of early initiation and ongoing treatment of Ocrevus on disability progression in both PPMS and RMS.

On the NMOSD side of things, what should the neurology community know about the latest findings from studies of satralizumab?

New longer-term data presented at ECTRIMS 2021 show that Enspryng is effective in significantly reducing relapses over four years of treatment in people with anti-aquaporin-4 antibody (AQP4-IgG) seropositive NMOSD, with a favorable safety profile both as a monotherapy and in conjunction with immunosuppressive therapy (IST).

Findings showed 73% and 71% of people treated with Enspryng in the OLE periods of the SAkuraStar and SAkuraSky studies remained relapse-free after 192 weeks (3.7 years), respectively, and 90% and 91% were free from severe relapse. The data also demonstrate a favorable safety and tolerability profile in the overall Enspryng treatment period of up to seven years, with rates of adverse events (AEs) and serious AEs consistent with the double-blind periods in both SAkuraStar and SAkuraSky studies.

The longer-term data further reinforce the previously observed efficacy and safety of Enspryng, which is the first and only approved treatment designed to target and inhibit the IL-6 receptor activity and the first and only NMOSD treatment administered subcutaneously every four weeks.

Transcript edited for clarity. For more coverage of ECTRIMS 2021, click here.