In October 2023, Genentech announced results from the first-ever clinical trial designed exclusively to enhance the knowledge base supporting the Black and Hispanic population living with multiple sclerosis (MS).
The Phase IV CHIMES—(CHaracterization of ocrelizumab In Minorities with multiplE Sclerosis)—trial evaluated Genentech’s drug Ocrevus (ocrelizumab) in Black and Hispanic/Latinx people with relapsing multiple sclerosis (MS). And the results tell us a great deal, both about the drug and about improving clinical trial diversity.
The results show that the drug effectively manages disease activity in these populations, which make up about 20% of the total disease population and face disproportionate risk of severe disease and disability. Notably, approximately half of all trial participants achieved “no evidence of disease activity” at week 48, and 94% experienced no relapses. The safety and efficacy were consistent with other studies.
Equally important, the trial sets a new standard for diversity and inclusion in clinical trials and provides insights on how to improve recruitment and retention among historically underrepresented populations.
Bio.News spoke with David E. Jones, Senior Medical Director and Manager of Neuroimmunology at Genentech, about their groundbreaking trial and what it means for the future of MS diagnosis and management.
Editor’s note: The Q&A below has been lightly edited for Bio.News style.
Bio.News: How is Genentech embracing diversity, and how does this relate to the CHIMES trial?
Black and Hispanic/Latinx people living with MS make up approximately 20% of the disease population, but they have historically been underdiagnosed, undertreated, and underrepresented in clinical trials. This is despite studies suggesting Black and Hispanic/Latinx people may experience more severe symptoms, faster disease progression, and a higher risk of disability than their white counterparts.
CHIMES was the first-ever clinical trial in MS which set out to understand more about these patient populations and to provide critical insights on biomarkers and how the disease behaves in this population, broadening our current understanding of MS disease biology. The results of the one-year analysis of CHIMES highlights data on how Ocrevus controlled disease activity (NEDA) and disability progression results in this population and provided invaluable insights that will help inform more personalized treatment decisions and potentially improve outcomes for people with MS in these underrepresented communities.
Bio.News: How does Ocrevus work? What are the risks and benefits compared with current treatment options?
Ocrevus is a therapeutic monoclonal antibody that targets a type of immune cell, called a CD20-positive B cell, which plays a key role in the MS disease process. The efficacy and safety data of Ocrevus support the approach of selectively targeting CD20-positive B cells as a therapeutic strategy for MS. CD20-positive B cells are a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage, which can result in disability in people with MS. Based on preclinical studies, Ocrevus binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved. Since the CD20 protein is not found in many other cells of the immune system, they can continue to fight infection. This pioneering science redefines our understanding of the underlying biology of MS and shows that B cells, a type of immune system cell, play a central role in the disease.
Long-term data continue to show a favorable benefit-risk profile for Ocrevus, which is the only aCD20 with over 10 years of efficacy and safety data, with patient-years of exposure exceeding 25,000 across all clinical trials and more than 300,000 people treated in over 100 countries worldwide.
Bio.News: What impact will the results of the CHIMES trial have on the Black and Hispanic communities?
Healthcare is not always equitable. The Black, Hispanic/Latinx, and rural communities often face inequalities that lead to less access and worse health outcomes. As a leader in MS, we’re actively working across the organization in collaboration with key stakeholders, including patients, advocacy groups, and healthcare providers, to help ensure that Black and Hispanic/Latinx people with MS have more equitable access to care. We have been listening to the needs of these communities to identify gaps and opportunities that help address these challenges and understand how to more meaningfully engage with these groups to improve diagnosis and patient treatment experience. The CHIMES trial, which heavily involved advocates from the moment of inception and through the process as part of our advisory board, is a key example of this, as learnings from this trial are being applied to ongoing Genentech trials as possible to ensure that we’re designing our trials to have the right support and structures in place to ensure equitable representation.
Beyond our clinical trial program, we work on educational materials for disease awareness in multiple languages.
Bio.News: How did Genentech proactively overcome barriers to recruitment and retention?
CHIMES was specifically designed in collaboration with people living with MS, advocacy groups, and neurologists to address barriers to clinical trial inclusion among Black and Hispanic/Latinx communities, including:
- Selecting study sites that serve large underserved racial and ethnic communities;
- Broadening study eligibility requirements;
- Using the appropriate laboratory reference ranges for the Black and Hispanic/Latinx population;
- Providing written materials and study websites in English, Spanish, and Swahili, keeping in mind linguistic and cultural sensitivity in all materials; and,
- Widening the screening duration to eight weeks and using visit windows of ±14 days to allow more schedule flexibility.
In addition, CHIMES included proactive measures to promote patient retention and decrease the burden on people enrolled in the trial, including as appropriate a stipend/compensation for loss of earnings, childcare reimbursement, flexible scheduling, accommodation, reimbursement for travel and meals and ride-share coverage for transportation when needed.
Bio.News: What were the expectations from the trial results for future management of patients with MS?
There has historically been limited data on MS in Black and Hispanic/Latinx populations impacting both our understanding of the progression of the disease and the effectiveness of treatment in these communities. The data from CHIMES provide invaluable insights that will help inform more personalized treatment decisions and potentially improve outcomes for people with MS in these underserved communities. These data support the efficacy and safety of Ocrevus in these patient populations, providing physicians with specific evidence to reference and helping to address historic distrust within these communities.
CHIMES also set out to evaluate biomarkers and how MS behaves in this population, broadening our current understanding of MS disease biology, and we anticipate that as these results are fully evaluated they will be able to provide greater insights into the management of MS in these populations. Supporting biomarker research is especially important for the Black and African American community, as compared to other patient populations (e.g. for Hispanic patients, we have been able to look at biomarkers from the LATAM community), we’ve traditionally been limited in our comparisons with data from a place of origin. CHIMES included trial sites in Kenya which continues to build our understanding of what MS looks like in the region. By enabling the examination of genetic profiles and ancestry as part of our research, CHIMES has enabled us to forge new, unchartered territory.
Bio.News: How did patient selection impact communication among the study participants?
We tailored our inclusion and exclusion criteria specifically for this population, and also implemented proactive measures such as building strong relationships and lines of communication with sites and participants, to overcome circumstantial barriers to successful enrolment and retention. Given that study enrolment took place during the COVID-19 pandemic, where clinical trial enrolment was universally a challenge, this over-enrollment ahead of schedule is particularly notable.
Additionally, all patients received Ocrevus while participating in the clinical trial.
Bio.News: How are insights from the CHIMES trial reshaping the future of other Genentech clinical trials?
One of our first actions in developing the CHIMES trial was to identify members of the Black and Hispanic/Latinx community, alongside community and academic practitioners who support these populations and bring them together as part of our advisory board. Their insights shaped our protocol at inception and throughout the trial, allowing us to both tailor the inclusion and exclusion criteria for the specific target population and to provide appropriate resources to address social determinants of health such as transportation, childcare, and the cost of missing work due to study participation, as needed.
Insights and key learnings from the CHIMES trial are being applied across the breadth of Genentech’s clinical program, including the Phase II FENopta trial in MS and the Phase IV ELEVATUM and BELVEDERE trials in Ophthalmology.