It may be half a decade since Genentech scored an FDA approval for its multiple sclerosis (MS) drug Ocrevus, but the Roche unit believes it still has a way to go to ensure the central nervous system disease therapy is targeted at all the right patients.
The company is focused on expanding the therapeutic landscape for MS patients, which involves moving away from a “one size fits all” treatment approach and building a more equitable offering for Black and Hispanic/Latino communities, Ashish Pradhan, M.D., executive director and MS disease area lead at Genentech, tells Fierce Biotech in an interview.
MS was traditionally considered more common in white people, particularly young white females. That assumption has played a role in the large numbers of white patients enrolled in clinical trials and under-enrollment of other groups. Of almost 60,000 published scientific papers about MS, fewer than 1% focused on Black and Hispanic American patients, according to a 2014 analysis.
However, data collected in recent years have overturned these long-held assumptions.
"MS tends to affect the Black community or the Hispanic community actually much more severely than the white population, although it tends to present itself a little late," Pradhan says. In the U.S., about a third of MS patients are Black or Hispanic, a proportion that underscores their glaring underrepresentation in clinical trials.
To combat this, Genentech is conducting the first study focused exclusively on further understanding MS disease biology among Black and Hispanic people, with an estimated primary completion date of June 8, 2023.
The single-arm, open-label phase 4 study of Genentech’s anti-CD20 monoclonal antibody Ocrevus, dubbed CHIMES, has been carefully designed after receiving feedback from local communities and advice from medical specialists to best improve access for Black and Hispanic patients, Pradhan says. The study is part of the biotech's broader shift toward more personalized approaches to Ocrevus trials, which also includes optimizing dosing approaches, specifically a higher dose and a shorter infusion.
It isn’t Genentech’s first diversity initiative tied to Ocrevus—the company recently launched Spanish direct-to-consumer advertising. The campaign aims to encourage early MS treatment and appropriate care via patient education resources and alongside Spanish-speaking patient support and access solutions.
"From a cultural point of view, we have a multichannel approach to addressing these healthcare disparities," Pradhan says.
Big Pharma has been slowly waking up to the problem of unrepresentative trials. Earlier this year, the FDA began encouraging drugmakers to submit racial and ethnic recruitment plans for their trials early in the drug development process in an effort to boost participation among underrepresented populations.
In fact, Black Americans make up 13% of the U.S. population but just 5% of clinical trials, according to a recent report from life science consulting firm Trinity Life Sciences. The gap is even worse for Hispanic or Latino Americans, who account for 19% of the population but just 1% of trial participants.
Against this backdrop, it's unsurprising that Genentech's attempts to grapple with the issue of patient representation aren't limited to MS. The company admitted that a phase 3 trial of its investigational Alzheimer's therapy gantenerumab was unable to recruit the kind of population that accurately reflected the degenerative condition's predominance in nonwhite communities. Genentech has since announced a dedicated study aiming to rectify this issue by enrolling a more diverse population.
When it comes to MS, there is still plenty of room for innovation, according to Pradhan, and Genentech hasn’t stopped exploring different possibilities to get the most effective treatment to patients.
“We listen to feedback, we listen to insights that we get from the field, and we continue to evolve our people development program based on those insights,” he says.
While other treatments have been approved for relapsing MS, Ocrevus is still the only therapy available for both relapsing MS and primary progressive MS, the most severe type of the disorder. Genentech thinks Ocrevus, which was approved for both indications in 2017, is still part of the evolving MS landscape, which is why the company is currently conducting high-dose clinical studies for the drug.
The company is also exploring other therapeutic pathways to address the condition, with Pradhan dubbing BTK inhibitors “the next step forward.”
The reversible inhibitors can prevent BTK activity, which inhibits B-cell receptor signaling and can stop B-cell malignancies from proliferating. Pradhan believes Genentech’s BTK inhibitor fenebrutinib’s dual mechanism of action could reduce MS relapses. The drug is currently being evaluated in a phase 3 development program consisting of three global trials: two in relapsing MS and one in primary progressive MS. In the latter trial, fenebrutinib is going head-to-head with Ocrevus.
“Long story short—we’re not resting on our laurels,” Pradhan says.