World Brain Day 2024
Established by the World Federation of Neurology in 2014, World Brain Day seeks to raise public awareness on various neurological health topics each year. This year’s theme, “Brain Health and Prevention”, brings awareness to preventive measures that can alleviate the burden of many neurological conditions for patients across the world. Notably, this initiative stresses that socioeconomic status or geographic location should not be barriers to prevention.
Across the spectrum of neurologic conditions, preventive healthcare takes many shapes and forms, from lifestyle modifications to therapeutic interventions.
For patients diagnosed with multiple sclerosis (MS), one of the most prevalent neurologic conditions worldwide, early intervention with a disease-modifying therapy (DMT) is a critical form of preventive healthcare, enabling many patients to live long, healthy lives. Fortunately, today there are a plethora of DMTs that dramatically slow and/or stabilise disease in many MS patients. Patients treated early in their disease course accumulate disability at a slower pace than untreated patients, keeping them out of wheelchairs and walkers for significantly longer periods of time.
Most neurologists nowadays favor an “induction” approach and treat MS patients with a highly effective DMT in frontline settings. Recent studies have shown that early implementation of high-efficacy DMTs in relapsing-remitting MS can lead to long-term clinical benefits such as improvements in disability and reducing risk of disease progression (source). In the past, concerns over the safety of high-efficacy DMTs caused many neurologists to start patients on lower efficacy DMTs; treatment change to a high-efficacy DMT was triggered mainly by disease progression. However, a multitude of studies have shown that the benefits of early treatment with high efficacy DMTs (for most patients) outweigh the safety risks, prompting a major shift in how MS patients are treated today (source; source). This concept of early aggressive treatment is becoming prevalent across neurology; “time is brain”, initially coined in stroke patients to emphasise the need for rapid action to prevent brain damage, is a key slogan in other neurodegenerative diseases, notably Alzheimer’s disease (AD). Compared to MS, the clinical evidence for current DMTs in AD is far less established, but already the concept of early treatment to prevent cognitive decline is a major narrative.
Despite these critical advances in treating MS, people of color tend to fall behind when it comes to early intervention with high-efficacy DMTs. Only 11% of Hispanic patients and 25% of Black patients start on high-efficacy DMTs, compared to 29% of non-Hispanic White patients (source). Underpinning this disparity is the fact that for many years, MS was incorrectly believed to be a disease that primarily affects White patients (source; source; source). Moreover, MS patients of colour have historically been underrepresented in clinical trials (source). This issue is not isolated to MS or even neurology; people of colour are underrepresented in clinical trials across therapy areas, to such an extreme that policy makers and regulatory agencies are now intervening to rectify these imbalances (source, source).
Addressing the disparity in clinical trial representation of people of colour is already underway, with several substantial investments to study people with diverse racial and ethnic backgrounds. One such landmark study (“CHIMES”) was recently presented at the American Academy of Neurology’s (AAN) annual meeting in April. Sponsored by Roche, CHIMES is a Phase IV study of Ocrevus (ocrelizumab) in Black/African-American and Hispanic/Latino individuals with MS. Ocrelizumab is the number one prescribed DMT on the market for MS and considered the gold standard when it comes to high efficacy. In Phase 3, ocrelizumab reduced annualized relapse rates by 46-47% compared to interferon beta-1a (source), but only ~5% of subjects in the pivotal trial program were Black (source).
The CHIMES study was designed to overcome common social and logistical barriers to clinical trial participation for these underrepresented groups. Study materials were reviewed for cultural appropriateness and made available in multiple languages. Financial compensation (for loss of earnings, childcare, travel and meals) and transportation were provided. Greater flexibility in screening criteria and visit schedule windows allowed for a more inclusive study population.
Initial data presented at AAN showed that the overall efficacy and safety of ocrelizumab in CHIMES aligned with results from the pivotal trials, and the trial hit its recruitment goal early.
While certainly encouraging, it is unclear to what extent the lessons from CHIMES are transferable on a broader scale, and importantly, to pivotal trials. With its remarkable clinical profile of high efficacy and safety, ocrelizumab is one of the most commercially successful DMTs ever developed, generating over $7B in sales worldwide in 2023 (source). It will not be feasible to provide the full suite of accommodations in CHIMES in the context of a multicentre, pivotal trial. And the fact that CHIMES was able to recruit patients so quickly is certainly tied to ocrelizumab’s reputation as the gold standard DMT. Nonetheless, there are certainly a few key learnings that should be considered when designing an inclusive clinical trial.
Enhancing diversity in clinical trials can be achieved by implementing patient navigators to boost retention (source), personalising education with multilingual materials like VISBL-MS, selecting trial sites in underserved communities, providing cultural competency training for staff, and partnering with patient advocacy groups and minority-serving institutions. These strategies ensure broader and more inclusive participation, leading to better health outcomes for all populations.
- Implementing patient navigators which can increase retention of diverse populations (source)
- Front loading and personalising patient education and providing multilingual materials (i.e. VISBL-MS)
- Identify trial sites in underserved communities
- Bias and stereotyping training to improve recruitment
- Partnering with patient advocacy groups and minority-serving institutions
- Leveraging health records to identify diverse populations for recruitment
- Reporting on outcomes in diverse and/or under-represented populations
Precision medicine is lacking in MS, and clinicians need biomarkers to detect MS earlier and guide treatment decisions. Future studies are needed in patients at higher risk of complications from long-term treatment with high efficacy therapies. Development of biomarkers that can guide decisions regarding treatment changes, duration and discontinuation protocols are needed. As the field looks toward precision medicine as the next frontier in the landscape of MS, it will be imperative to design trials that are both inclusive and capture the true diversity of patients in the real world.
Neuroscience continues to be one of Deallus’ leading therapeutic areas, both in project volume and the expertise held by our consulting staff. We’ve had the privilege of partnering with many pharma organisations over the years as they navigate the challenges and complexities of drug development and commercialisation within neuroscience.
Authors – Anna Scott and Brenda Abdelmesih
July 2024