Health equity and clinical trials: A conversation with Jamie Freedman, MD, PhD, and Shalini Mohan, MD

"Let’s Talk," a series from Optum Life Sciences, offers thought-provoking insights and discussions that capture what’s on the minds of life sciences leaders. These articles feature biopharma innovators we work with every day. Our latest interview features Jamie Freedman, MD, PhD, a recently practicing hematologist-oncologist and former senior vice president and head of U.S. medical affairs at Genentech, and Shalini Mohan, MD, executive director, head of health equity and inclusive research at Genentech.

Dr. Freedman's recent position focused on improving access to clinical trials and medicines for all patients, including historically underserved populations. From clinical trials at community-based hospitals to research in Kenya and South Africa, his work has continually challenged myths and assumptions around conducting clinical trials. Now he hopes to take his work a step further by creating a new business model to improve drug access in Africa. 

In her current role, Dr. Mohan focuses on opportunities to address barriers at the patient, provider and institution level that hinder health care access for underserved populations. She was previously a medical leader for tocilizumab and multiple other immunological indications, including the treatment of COVID-19 pneumonia. She conducted the largest randomized placebo-controlled trial for underserved patients, including Hispanic, Black, Native American and rural populations.

I enjoyed learning about their journeys in health equity and the clinical development myths they’ve shattered along the way.

How did your work become more focused on health equity initiatives during your time at Genentech?

Dr. Freedman: For the majority of my career, I focused on executing clinical trials and generating high-quality data as quickly as possible. We went back to the same large academic medical centers because we knew the investigators, and they could quickly enroll patients. But those populations tend to be very homogeneous and almost entirely white.

It wasn’t until the COVID-19 pandemic hit in early 2020, soon after I’d joined Genentech, that health equity became a significant part of my work. We heard that one of our products, Actemra (tocilizumab), an interleukin-6 (IL-6) receptor antagonist for rheumatoid arthritis, was being used around the world off-label for patients with COVID-19 requiring hospitalization. Anecdotally, we heard stories of patients who were benefiting from this treatment, but we didn’t know for sure.

Then Roche, which owns Genentech, started a pivotal trial to assess the risks and benefits of Actemra for this purpose. Using real-world data, we discovered early on that Black patients in the U.S. were hospitalized for COVID-19 at disproportionately higher rates, when compared to white patients. And there was a fairly strong signal early on that they were less likely to receive targeted immunotherapies.

How did the pandemic affect your next steps once you discovered this disparity?

Dr. Mohan: We needed to act quickly during the pandemic. It was such a dire situation, and patients were filling up the ICUs. There was a ventilator crisis in New York City. At that time, we started a separate clinical trial on Actemra, focused specifically on underserved patients, called EMPACTA (Evaluating Minority Patients with Actemra). It was a multicountry, placebo-controlled, randomized phase 3 clinical trial where we investigated the safety and efficacy of tocilizumab in hospitalized patients with COVID-19 pneumonia who were not receiving mechanical ventilation. We focused on enrolling patients who were historically underrepresented.

It's probably the most rapidly accruing trial we've ever done. We recruited almost 400 patients in a very short time, and 85% of our participants were from underserved, racial and ethnic minority populations. The trial was unique in that it was patient-centered with minimal procedures and a simple objective endpoint to determine whether Actemra could reduce the need for mechanical ventilation, and it did. In conjunction with other work, the trial ultimately led to an approval for Actemra for the treatment of COVID-19 pneumonia.

In the process, we broke long-held myths that you can't enroll patients from underrepresented groups and generate high-quality data. It opened the door to doing more inclusive research trials. It was a landmark study that I was really proud of — probably the thing I am most proud of in my entire career to date.

What else did you learn from EMPACTA?

Dr. Mohan: EMPACTA was different from a lot of clinical trials in that patients were already in the hospital rather than out in the community. We didn’t have to go out and find them like we do when we’re studying a chronic disease. Perhaps not surprisingly, what we found in those patient populations was a lack of trust in clinical trials, and generally a lack of trust in the health care system. We subsequently showed that we could also replicate patient-centered clinical trials for chronic diseases like multiple sclerosis, diabetic macular edema and cancer in the community.

In the hospital, these patients were so sick, but it was still very important to get their consent. To build trust, we worked with staff from similar cultural backgrounds as the patients we wanted to study, and we had those culturally aligned staff members discuss the clinical trial directly with the patients. We learned that, to expand diversity in trials, the sponsor has to be more hands-on than in a traditional trial, and you have to provide additional support as needed.

Some of the hospitals we went to in the city weren’t as resourced as the large medical centers we typically partner with on trials, but we provided the additional resources needed to enroll patients. It’s a misconception that community-based hospitals can’t do clinical trial work. They don’t typically get to participate in the big trials from pharmaceutical companies, but that doesn’t mean they can’t.

Given the additional investment and personnel required to conduct a clinical trial like this, why is it important to continue these efforts?

Dr. Freedman: When we work with these community hospitals, we learn more about what they need to run successful trials, and then we can proactively provide those resources. It’s an ongoing investment. At new sites, clinical monitoring tends to be more intensive, so yes, it will require additional personnel time. Initially, it will be more expensive. So, the question becomes, what’s the business rationale for doing this?

First and foremost, it’s about doing the right thing for patients. It’s also an opportunity to increase access and grow the market for a particular product. It’s a win-win for patients and for companies.

That’s why it makes sense to invest long-term, and as we build trust within more of these communities, the return on investment will grow over time. We shouldn’t be competing with other companies around health equity. All companies can work together to solve this issue because one company can’t solve it alone.

What led to the expansion of the work from the U.S. to Africa?

Dr. Mohan: In going out to these underrepresented community-based hospitals, we had the right intent. But there were many companies working on drugs for COVID-19 during that time. As the pandemic started slowing down in certain areas and then picking up in others, we had to chase the virus across the country, from state to state, to find patients.

But eventually, enrollment in the trial started slowing down. We then thought about going to other countries that didn’t have access to Actemra. We went to certain South American countries, as well as to South Africa and Kenya, to enroll patients. The most surprising opportunity was in Kenya, because Kenya had never been part of a phase 3 global clinical trial before, at least not that we knew of. Our efforts were motivated by a continued desire to find underserved Hispanic and Latino American patients, as well as Black patients, whether they’re from the U.S.,South America or Africa.

What were your takeaways from the work you did in Africa?

Dr. Freedman: There was skepticism about whether we could conduct these clinical trials successfully in other countries. Since then, Genentech has done many more trials in Kenya. Several institutions in Africa have the infrastructure to conduct certain kinds of clinical trials. Through this experience, I was struck by how few patients had access to medicines, in part because the drugs weren’t even approved in the countries where they lived.

It takes a very long time to get drugs approved in Africa. There’s an opportunity to speed up drug approvals and increase access. The reimbursement model probably just needs to be different in Africa than the rest of the world. Africa represents about 20% of the world’s population, but only 2% of Africans end up in clinical trials.

I think Africa presents probably the biggest clinical trial opportunity over the next 20 to 50 years, because it has a large and rapidly growing population, and those citizens represent such a big part of the population who don’t have access to our drugs today. We have to solve that together. But I think companies are still very cautious about what they do there.

How have these experiences shaped your future goals?

Dr. Freedman: I was at Genentech for nearly 4 years, and I felt that my team and I played a major role in driving changes that eventually became more self-sustaining. More clinical trials are now focused on underrepresented populations. There’s also a broader recognition of the importance of Africa in pivotal trials.

I came to realize that there’s something more I can do around health equity outside the company where I can add even more value. So right now, I’m working with some former Genentech colleagues on a new business model for access to drugs in Africa. First, we need to find investors that believe in this, and we need to collaborate and partner with other institutions and pharmaceutical companies to make it happen. I don’t know how far it’s going to go, but I am motivated to do something more impactful in this space.

Dr. Mohan: I’m really proud to work for a company that prioritizes addressing barriers to health care access for underserved patient populations. I’m currently leading a study called CATORI (Study to Characterize Access to Specialty Care Received by American Indians/Alaska Natives) that aims to understand patient barriers to accessing care from a specialist such as an oncologist, neurologist or ophthalmologist. This study exemplifies our commitment to advancing health equity as it’s a non-interventional trial focused on patient perspectives. It will inform how we conduct future clinical trials to improve representation for this group as well as other underrepresented populations.

We’ve made significant progress in advancing health equity through our inclusive research efforts and aim to embed the best practices we’ve learned across all our trials, so they are representative of the patients and populations that experience disease. We are also seeking opportunities to work with external stakeholders across different sectors. As Jamie mentioned, no one company can do this work alone, and cross-sector partnerships will enable us to unlock sustainable and scalable solutions.

I believe organizations like Optum and Genentech can work together so all patients get the best possible care.

Disclaimer: At the time of the interview, Dr. Jamie Freedman was not employed by Genentech. The interview represents the opinions and views of Dr. Freedman and does not necessarily represent or reflect the views, opinions, policies or positions of his former employer Genentech. The interview represents the opinions and views of Dr. Shalini Mohan, a current employee of Genentech, but does not necessarily represent or reflect the views, opinions, policies or positions of Genentech.

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