The COVID-19 pandemic introduced novel challenges for global biopharma organizations, as many adapted their clinical trial operations while working to develop lifesaving interventions. At Gilead Sciences, this need to quickly pivot led to an increased understanding of how real-world evidence (RWE) can inform research and development (R&D) by enabling more diverse populations to participate in studies and by powering insights on the real-world performance of treatments.
For Gilead, this included VEKLURY® (remdesivir)—which the U.S. Food and Drug Administration (FDA) approved as the first antiviral treatment for COVID-19—as well as other therapies in their portfolio, which spans HIV/AIDS, liver disease, oncology/hematology, cardiovascular, inflammation/respiratory, and other therapeutic areas. Gilead is working with Aetion and HealthVerity to generate RWE.
In October 2020, Diana Brainard, M.D., Senior Vice President and Virology Therapeutic Area Head at Gilead, joined the second annual Aetion Summit, “Evidence at the Apex,” to discuss how RWE advances clinical research at Gilead amidst COVID-19, and how real-world data (RWD) can shed light on how treatments perform in practice.
Read on to learn from the insights Dr. Brainard shared at the Aetion Summit, including lessons learned while shifting to remote clinical trials, how cross-functional partnerships have shaped the industry’s understanding of COVID-19, and how she and Gilead are looking to RWE to understand how remdesivir performs in diverse patient populations—and to expand its use into the outpatient setting.
Responses have been edited for clarity and length.
Q: What have you learned so far from your rapid work to develop COVID-19 interventions?
A: We’re learning a lot of digital lessons in our ongoing non-COVID trials. We had to completely reimagine many studies due to COVID-19, so we shifted to telemedicine, shipped drugs to people’s homes or pharmacies, and created new models for safety monitoring and information gathering. Looking back, we’ve learned that much of clinical trials can be done remotely.
This is beneficial for a large segment of the population, and is one of the positive changes driven by COVID-19. For example, people who experience economic hardship may find it burdensome to participate in clinical studies. But if they’re able to do it from home, on their own schedules, we’ll likely see improved diversity and inclusion in clinical research. Across our research programs—and as we consider expanding remdesivir’s indication into the outpatient setting—we’re thinking creatively about how we can make trials informative while offering study options that encourage participation.
Q: How can cross-industry partnerships help more effectively harness the power of RWE to address COVID-19?
A: In addition to leveraging existing partnerships with hospitals and other groups, we’ve also entered new collaborations to increase our understanding of COVID-19. One partnership that has been particularly helpful in this effort is the Reagan-Udall Foundation for the FDA and Friends of Cancer Research’s COVID-19 Evidence Accelerator.
This partnership has moved the needle for us in terms of understanding how to identify COVID-19 patients within RWD, use those data as effectively as possible, and sync with regulators and industry leaders in real time. In the past, we’ve had to do this work in a stepwise fashion—a time consuming process, which, in turn, impacted development decisions. We had to choose whether we would take the extra time to forge ahead with RWE—something considered untraditional in the virology space—or continue with the traditional, accepted methods. Through our work with the COVID-19 Evidence Accelerator, we’ve been able to do both, because all of the key stakeholders are at the table together.
Q: How did you ensure that diverse patient populations were represented in clinical trials as you developed remdesivir?
A: We are committed to ensuring that the populations we study in clinical trials look like the populations that will be treated with our products. This is especially important in the context of global trials; study populations must be representative of real-world populations not only in the U.S., but also across Europe, Asia, and other geographies.
As we look to expand remdesivir into the outpatient setting, we’re thinking through how we reach the communities—specifically, communities of color—who are greatly affected by COVID-19 but often aren’t included in outpatient trials. To do this, we’re analyzing the RWE on remdesivir, which is showing similar outcomes to clinical trials, and we’re publishing these findings to publicly communicate that the drug works across diverse populations.
Q: How can RWE inform COVID-19 drug development and commercialization, and how do we move this forward post-pandemic?
A: Our first inklings about the effectiveness of remdesivir came from early compassionate use case reports. We then turned to RWD to see if we could gather any information on COVID-19 in hospitals. This was challenging early on in the pandemic, as it was difficult to identify patients and source other key information, like patients’ oxygen levels.
It’s amazing how much progress has been made in the past year. Data access has improved, and the industry has also recognized and acknowledged the complicated issues that come with using COVID-19 RWD, including geographic and temporal differences in care and outcomes.
Partnering with organizations like Aetion has helped us understand the natural history of the disease, as well as how remdesivir is used in the real world. We were able to tap into key data sources to understand, early in the emergency use authorization, that remdesivir was being reserved for the sickest, mechanically ventilated patients due to the supply shortage—even though the data suggested that the drug performed best when used earlier. We brought that data to the National Institutes of Health (NIH) and the White House to ensure that the drug was used where and when it could have the greatest impact, and the NIH incorporated this information as it developed guidelines to maximize the drug’s benefit.
Now we’re focused on using RWD in additional studies to learn how remdesivir impacts vulnerable populations. For example, we’re asking whether remdesivir can be used for patients with renal failure, or for pediatric or pregnant populations, and how we can recruit similar patients for clinical trials as we look ahead.
Q: In the future, how can we navigate the challenges of working with RWD and communicate its potential to inform drug development?
A: While the public and scientific communities are generally aware of how clinical trials work, there’s a lot more to drug development and to understanding outbreaks than randomized controlled trials. We need to do our part to help educate people about other types of clinical studies, because they can differ greatly from the trials people are used to hearing about in the news.
Specifically, we need to start educating the public about RWD analyses, pragmatic trials, and vaccine trials, and lay the groundwork now before we have results to share. Identifying eligible patients in RWD is not as straightforward as it sounds, so we should communicate the meaning of inclusion and exclusion criteria, the importance of following good clinical practice, and other factors that inform the quality of the data.
In addition, if we’re able to work as an industry to validate real-world endpoints, we can help make the data useful from a regulatory standpoint. This will also align well with the mandate for value demonstration post-approval. If we can match approvable endpoints with meaningful RWD—for example, the complex constellation of endpoints required for rheumatologic diseases, which are collected through X-rays and other tests—we can more seamlessly connect which drugs get approved with what happens in the real world. This will be a win for biopharma, regulators, and patients.