Putting biomedical research advances within reach

Penn Medicine has a remarkable track record developing therapies that receive FDA approvals, including pioneering whole classes including cellular and gene therapies and mRNA vaccines. Even so, faculty remain humbled by one basic tenet: Advances mean nothing if patients can’t access them.

“If our goal is to improve human health, we cannot call ourselves successful unless we bring the fruits of our labor to bear as broadly as possible on people suffering from the conditions that interventions are designed to treat,” said Emma Meagher, MD, senior vice dean for clinical and translational research in the Perelman School of Medicine.

In the U.S., manufacturers are free to set prices for brand-name drugs and launch novel products at the highest rates, with gene therapies often costing millions and chimeric antigen receptor (CAR T) treatments approaching the half-million-dollar range. Although some manufacturers offer payment assistance programs, these expenses burden state and federal health programs, private insurers, and uninsured or under-insured patients facing out-of-pocket costs.

Commercialized drug prices are beyond an academic institution’s control, but researchers — including many at Penn — are exploring advances that would make cutting-edge treatments more easily available to everyone who needs them. In the case of CAR T, for example, those working to develop a universal version of the therapy understand they can drive down costs by transforming a time-intensive, personalized treatment that requires a patient to donate their own T cells into one where an existing bank of cells could be used to treat many patients.

Many U.S. cancer patients who are eligible for today’s FDA-approved CAR T therapies do not actually receive the treatment or end up waiting months to begin the process as their disease worsens. Honing an “off-the-shelf” version of CAR T therapy would also curb the extensive wait times and manufacturing limitations that prevent many patients from getting the treatment.

Clinical trial outreach

Racial and ethnic health disparities also stoke accessibility concerns. Black Americans are less likely than any other group to receive CAR T cell therapy—a trend rooted in gaps in income, education, housing, job security, and proximity to high-quality medical centers. These same social determinants of health have also led to their underrepresentation in CAR T and all kinds of clinical trials; Black patients account for just 5 percent of clinical trial participants nationwide.

“Black patients’ historically low participation in trials means that, compared to white individuals, they have less access to some of the most advanced new treatments,” said Carmen Guerra, MD, MSCE, vice chair of diversity and inclusion in the Department of Medicine and associate director of diversity and outreach at the ACC.

To better diversify clinical studies in cancer, the ACC recently conducted a five-year community engagement study that reached more than 10,000 individuals through marketing campaigns tailored to minority cultures; wellness forums and events in Black communities; partnerships with Lyft and Ride Health to reduce transportation barriers; and patient education efforts. By the end of the project, the number of Black patients in Penn’s cancer clinical trials had doubled.

Additionally, the ACC piloted a Cancer Clinical Trials Community Ambassador Program that trained Black cancer survivors and caregivers in how to inform their networks about the importance of clinical research; a Genentech Innovation Grant launched in February is now fueling a study to determine how effective these peer ambassadors are when matched with newly diagnosed or relapsed breast cancer patients. And a first-of-its-kind collaboration with the Lazarex Cancer Foundation allows Penn to reimburse trial participants for gas, parking, plane or bus tickets, hotels, and other out-of-pocket travel and lodging costs related to clinical trial participation for the patient and a companion.

“There is financial toxicity associated with participating in a clinical trial, even though the actual treatment is covered by research dollars,” Guerra said. “We're working to eliminate obstacles one by one to make sure people can get the treatments they need. Addressing inequities is like an onion—we peel off one layer of barriers, then see what's underneath so we can address the next layer.”

Global access concerns abound, as well. Outside the U.S. and other economically stable nations like China, Australia, Singapore, and the United Kingdom, CAR T cell therapy is unavailable. Penn Medicine and CHOP have begun to partner with low- and middle-income nations in an attempt to facilitate global equity in CAR T cell research and treatment. Their first agreement is with Costa Rica's Social Security Program, the Caja Costarricense de Seguro Social; the partners will bring adult and pediatric patients to Penn or CHOP, where their immune cells will be collected for manufacturing into CAR T cells. Then, those cells will be returned to Costa Rica for infusion as part of a trial to be conducted there.

Democratizing vaccine access

Even when drugs are relatively affordable and easy to produce, racial disparities persist—disparities Penn Medicine is striving to overcome. Following the approval of mRNA vaccines against COVID-19, for instance, the health system worked with partners in West and Southwest Philadelphia to bring vaccines directly to their predominantly Black communities in spaces like gyms and public schools, and later moved portable “hyperlocal” clinics between locations like fast-food restaurants and retail parking lots in neighborhoods where many residents remained unvaccinated.

And like with CAR T, the global distribution of mRNA vaccines is far from equitable. By the end of 2022, at least three-quarters of the population in dozens of countries had been fully vaccinated—but in many others, mostly in Africa, only small fractions had received vaccines.

More than three years after COVID-19 first emerged, close to one-third of the global population has not yet had a single dose. That’s a big problem, said Drew Weissman, MD, PhD, the Roberts Family Professor of Infectious Diseases at Penn who made crucial mRNA discoveries that made these new vaccines possible, alongside Katalin Karikó, PhD, an adjunct professor of Neurosurgery.

Weissman has collaborated on research and drug development with more than 200 academic and biotech labs “on every continent except Antarctica” and has helped foreign governments set up Good Manufacturing Practices (GMP) sites where scientists in underserved areas are trained to produce and administer vaccines. Working with investigators at the vaccine center at Chulalongkorn University in Bangkok, he established a quality manufacturing center to produce an mRNA COVID-19 vaccine for Thailand and seven surrounding low- and middle-income countries, and he has done similar work in Africa and eastern Europe.

“Part of the failure in clearing COVID-19 has been a lack of vaccine access in many regions of the world where unchecked virus replication led to new variants,” he explained. “Local groups and governments being able to make their own RNA vaccines is critical for equity. I also believe these GMP sites will offer regions the ability to make vaccines against local diseases that Big Pharma has no interest in, such as dengue and tularemia in Southeast Asia, and malaria and a variety of local pathogens in Africa.”

More work to be done

Efforts at Penn to understand gaps in new drug access go as far as examining how and where products end up being prescribed. For example, researchers found in a spring 2022 study of the first-ever mutation-targeted bladder cancer drug that it was being used by fewer than half of patients who tested positive for the gene mutation in question and qualified to take it. Fewer than half of those potentially eligible even underwent testing.

The next step: figuring out why more people aren’t accessing a drug that could extend or save their lives and how to help close the gap—in this example, by advocating for more genetic testing and education for treating physicians.

“In academics, our incentive mechanism is to publish, to write grants, to see patients, and to teach,” Meagher said. “But if community isn’t an integral, systematic part of our processes, we aren’t doing our jobs to the best of our ability. If you believe what you're working on is important, you must bring it to all the people it will benefit.”