Innovation in
Drug Research and Development for Prevalent Chronic Diseases

Living With A Chronic Disease

Christin Veasley, Chronic Pain Research Alliance, spoke about the experience and frustration of living with chronic pain, and emphasized the value of including the perspective of people who have lived experience with chronic conditions. There is little information about the underlying biological mechanisms and causes of chronic pain, and animal models, translation, and research investments are insufficient, she explained. She pointed out that basic research tools (e.g., animal models) are not built to address questions about multimorbidity; and that clinical trials are often not adequately powered to assess disease heterogeneity and often exclude people with multiple chronic conditions.

Veasley said the goal should shift from finding a cure to determining how to live well with a chronic condition. She concluded that this shift will require changing the entire system, not just addressing the issue disease by disease. She added that this type of systems-level change will involve collaboration across different entities working as patient and advocacy organizations to examine each level of the drug R&D process to identify what needs to happen, who should take action, and how to incentivize that action.

Opportunities for People-Centered Drug Research and Development

Several speakers highlighted the importance of not only including patients in the drug R&D process as equal collaborators, but also of ensuring that the clinical trial enterprise achieve representative diversity in order to develop innovations that are relevant for people living with prevalent chronic diseases. Karen Winkfield, Meharry-Vanderbilt Alliance, expressed hope that researchers, regulators, clinicians, and patients can begin to think more critically about a people-centered approach to the design and implementation of clinical trials. She stated that engaging patients means engaging people from different communities, and she emphasized the need to hear from underserved communities to better understand the underlying issues that lead to disparities in engagement in clinical trials.

Erica Woodahl, University of Montana, described a community–academia partnership between the University of Montana and Native Americans belonging to the Confederated Salish and Kootenai Tribes. She explained how a community advisory board meets with the researchers every month to talk about research progress, recruiting, new grant opportunities, and other relevant matters. The researchers have held genetic education workshops to provide opportunities for community advisory board members to learn about genetics and gain some hands-on training, and community advisory board members visited Woodahl’s lab at the University of Montana to see how the samples are stored and processed. Woodahl stressed the importance of this community engagement as core to her team’s community-based participatory research model.

Jason Mellad, Start Codon, emphasized the importance of considering population diversity throughout the drug R&D lifecycle, including preclinical work. “It is not enough to find the individuals to be in your trial once you have a drug that is ready to go to market or diagnostic,” he said. “You need to also be thinking about [diversity] when it comes to the biomarker discovery or therapeutic discovery upstream in the preclinical phase.” Woodahl described problems with the lack of inclusivity in large-scale genetic studies, adding that it is unclear whether medical innovations coming out of such studies will be as useful for populations for which there are few available data.

Innovation In Drug Research And Development

Qi Liu, U.S. Food and Drug Administration (FDA), laid out three categories of new innovations that she said could help lead to new treatment options if adopted in drug R&D for prevalent chronic diseases: (1) therapeutic modalities (e.g., antibody-drug conjugates), (2) types of data (e.g., real-world data), and (3) analytical tools (e.g., artificial intelligence [AI]). Elizabeth Kunkoski, FDA, offering a regulatory perspective, explained that the technology used by researchers in clinical trials does not necessarily need to be approved by FDA or cleared for marketing. Instead, the main focus should be on whether the technology can provide sufficient high-quality evidence for FDA to be able to draw conclusions about the safety and effectiveness of a given therapeutic intervention. Speakers offered examples of how these three categories of innovations could be applied to chronic disease space to overcome barriers to innovation.

New Therapeutic Modalities

Grace Colón, InCarda Therapeutics, focused on the development of new therapeutic modalities, explaining that alternative routes of delivery and new modalities for existing drugs are two areas of promise. The use of novel biomarkers and integrating multiple biomarkers could lead to new endpoints and perhaps combination endpoints. These approaches could be integrated with digital health tools that provide better patient-reported outcomes and patient quality metrics. Holistic solutions “will require an integration of science, engineering, and medicine to address these problems together,” Colón said.

New Types of Data

John Ngai, National Institutes of Health, highlighted a number of data repositories from the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative that collect and share large varieties of data such as transcriptomic data, microscopy imaging, and neurophysiology information. He emphasized the need to make technologies more accessible to all people and engage communities that have traditionally been underserved and underrepresented as true partners so that the work of the BRAIN Initiative can benefit all.

New Analytic Tools

Andrew Radin, Aria Pharmaceuticals, explained how AI applications offer an opportunity to address unmet medical needs by better understanding the biology of disease with the use of computational modeling systems. He added that this approach was able to identify more candidate molecules than traditional approaches, which typically requires far more in vivo testing to find one or two candidates. Radin emphasized that this work may not only lead to the discovery of new treatments, but it can also help the scientific community gain new insights into the biology of these disease areas.

Barriers To Investment

Kirsten Axelsen, American Enterprise Institute, described how drug development decisions balance the cost versus the likely benefit of developing a particular drug for a particular disease, with the potential market size for the drug being a crucial factor. Given these parameters, she suggested that it is no surprise that the current system favors cancer drugs over cardiovascular disease, diabetes, mental health interventions. Further explaining the limited investment in R&D for prevalent chronic diseases, Susan Schaeffer, Patients’ Academy for Research Advocacy, noted that the lack of investment can be attributed to a few factors, including a lack of biomarkers for measuring disease progression and for measuring the progress in clinical trials, and inadequate animal models or other preclinical tools for interrogating the disease.

Opportunities for Incentives

Russ Paulsen, UsAgainstAlzheimer’s, said that knowledge de-risks the development of new drugs and diagnostics, and investment follows. Schaeffer highlighted that one key to investment in the chronic disease space has been biological discoveries that opened up new targets and new pathways for intervention. The other key was the belief that investors would be able to access return on investment for new treatments. Axelsen pointed to the rapid development of COVID-19 vaccines, which was spurred by a confluence of factors needed for rapid drug development: a belief that a market exists for the intervention, a mechanism for reimbursement, regulatory flexibility, and governments willing to pay for it.

One of the major health care trends that Mellad observed is the shift toward personalized medicine. The government played an important role by enacting the Orphan Drug Act, which provided incentives for innovations to treat rare diseases. Mellad suggested that this model could be applied to spur innovation in the chronic disease space. Ken Ehlert, UnitedHealth Group, shared a similar sentiment, suggesting that developers and other stakeholders in R&D move beyond thinking in terms of one therapy for treating 30 percent of the market and instead find ways to treat segments of the population. For example, large pragmatic trials that include participants with comorbidities who are taking multiple medications, he said, could lead to a better clinical understanding at the time of marketing approval for how new treatments can best be used in individual patients.

Case Studies

Robert Coughlin, JLL, shared the story of his son, Bobby, who was diagnosed with cystic fibrosis, and the struggle his family endured in finding a treatment. Coughlin said he had not realized that it would take advocacy, fundraising, and an average of 10 years and $1 billion—or more—to develop a new drug. “I realized the system wasn’t very efficient,” he said. “It didn’t work very well. The drug discovery process was hard.” The Cystic Fibrosis Foundation, which makes early-stage research investments to reduce some of the risk for companies and incentivize innovation in this space, was key to spurring innovation in drugs that could change the course of the disease. The investment and advocacy paid off when in October 2019, FDA approved Trikafta for the treatment of cystic fibrosis.

Raolot Abdulai, Sanofi, discussed the development of PROactive, a digital health tool designed to more effectively assess physical activity and independence in patients with chronic obstructive pulmonary disease. The tool was the result of collaboration among multiple actors, including patients, which allowed the developers to uncover an area of unmet need. She described how PROactive incorporates a traditional questionnaire and new digital health technologies and can now be used in clinical trials and beyond.

Robert Heine, Eli Lilly and Company, suggested the value of designing and carrying out studies that are focused on total disease burden rather than individual indications, using obesity and obesity-related disorders as a test case. Given that patients may be suffering from chronic kidney disease, cardiovascular disease, and diabetes, clinical trials would ideally examine outcomes relevant to patients with comorbidities. As experience with bariatric surgery has demonstrated, it may be possible to use real-world evidence and pragmatic trials to demonstrate the effectiveness of some of these medicines. “This is a challenge,” he said, “but also an invitation to everyone to start thinking about other ways to develop drugs for this metabolic disease that poses a huge challenge to the whole society.”