Important Ethical Questions Concerning CGTs
By Tyler Menichiello, contributing editor
I attended some great sessions at this year’s Meeting On The Mesa in Carlsbad, CA. My favorite was, perhaps, the hour-long panel discussion, The Importance Of Ethics In Gene And Cell Therapy. Moderated by Alliance For Regenerative Medicine (ARM) CEO, Tim Hunt, this panel included Benjamin Hurlbut, Ph.D., associate professor in the school of life sciences at Arizona State University; Janet Lambert, former CEO of ARM; Rob Perez, operating partner at General Atlantic and founder/chairman of Life Science Cares; Tay Salimullah, VP and head of global value access at Novartis Gene Therapies; and Durhane Wong-Rieger, Ph.D., president and CEO of the Canadian Organization For Rare Diseases.
While deliberating such nuanced and subjective topics like ethics doesn’t necessarily yield solutions to the problems we face as an industry, I think this discussion highlighted important questions we should be asking ourselves. Is our current healthcare system sustainable when it comes to supporting these therapies? How do we bring these (expensive) therapies to patients who need them most? How do we determine which patients are most in need? In an industry that promises to one day prevent all genetic diseases, which diseases should we prioritize in the present? When justifying market value, is the right way to think about human life in terms of healthcare costs saved and future economic productivity?
As Hunt said in his opening statement, “We are in the business of permanently altering people’s DNA. This is not a trivial undertaking.” These questions are important, not only as they relate to patient care, but for the trajectory and continued growth of our industry. “Lives are at stake,” Hurlbut said. “Ethics requires engaging in challenging conversations — not hiding from them, not putting them off, not shunning them — but embracing them, and engaging in them, even when there’s the possibility that they may engender controversy.” When navigating these complexities, Perez said, “having an ethical compass really does help to make the complex simple.”
“You cannot devolve ethics to a set of principles or guidelines, even really to a set of best axioms. At the end of the day, one can always find two ethical principles that oppose each other — do the most good for the most people, or leave no one behind. Take care of those who are the most in need or put the resources to where you know you can get the likelihood of the best outcome. They’re almost opposed in some respects,” Wong-Reiger explained. “Not even people in the wealthiest, most-developed countries with the best healthcare systems are going to get access. So, what does that really mean when we talk about trying to take an ethical approach? For me, ethics is highly personal, especially to the person you’re trying to engage in terms of what is the right decision. For me, it’s always helping people understand what the scenario is and helping them get to the best decision for them personally.”
Can Our Current System Support Cell and Gene Therapies?
A large part of the discussion centered around the shortcomings of our current healthcare system — specifically, as it relates to accessibility for patients. Our industry is developing 21st century medicine within the framework of a 20th century healthcare system. Salimullah perfectly described this predicament with an analogy, saying “it almost feels like we’re trying to develop some Star Trek kind of technology in a Flintstone-like movie.” As more gene therapies get approved for a wider range of conditions — and at increasingly high price points — the sustainability of our current healthcare system will be severely tested.
Hurlbut spoke to this point, saying we need to question whether the way we’re innovating is suited to our goals of healing and treating people. “If it isn’t, then it’s not good innovation because it’s not going to serve people as well as it should,” he said. “I think it’s incumbent upon this sector and all the different stake holders to ask pretty hard questions about whether the way business as usual is playing out is indeed the best way.” Hurlbut said our current system is unsustainable in the long run if the promise of our field is to play out over the coming decades. “Society is arranged in such a way that it cannot benefit from the good things its investments are producing, and that is a bad thing. That is a failure.”
According to Hurlbut, no singular actor is responsible for putting this current system in place. Rather, it’s the result of the community’s collective actions. He believes there’s a lack of responsibility and compassion being baked into our way of doing things. Such failures need to be addressed now, as we’re laying down the groundwork for our industry’s future. “It will be too hard to backtrack once the infrastructure is built.”
Wong-Rieger said she thinks the failure is on companies for not investing in access and proposed the idea of a collective starter fund. “What if we actually had a bucket of money where we can say, okay, here’s your investment to develop the therapies, and now here’s your investment to bring the therapies to people?” Continuing along the vein of collective support, Perez drew a comparison to the United States’ disability insurance. U.S. citizens collectively pay into disability insurance because we understand that injury and disability can randomly happen to any of us. He argued that this “randomness” exists in the rare and genetic disease space. “I wonder if we’ll ultimately get to a solution like that where we all say look, this can happen to any of us, so what if we all put a little bit in?” While we don’t want to stifle innovation, he said, “we want to make sure the innovation is there for our family,” should this randomness fall on us.
While there is definitely “sticker shock” associated with current cell and gene therapies (CGTs), Lambert made a good point that “it’s a privilege to talk about pricing, because it means you have a thing that you’ve priced,” meaning a therapy that’s working and has value. When it comes to life and death, she said, patients aren’t concerned about price; “they’re worried about if there’s something available for them.” She went on to say that we’re still very much in the early days — we don’t know yet whether the system can or cannot handle CGTs. What we know is there aren’t enough therapies available for the system to have adapted to it. “Payers will tell you that,” she said. “We’re still limping along pretty significantly in a one-off system that’s brutal for everybody.” However, she’s optimistic that when our industry and available therapies reach a “critical mass,” and it makes sense for payers (public and private) to adapt and finance these therapies, they will do so.
Leveraging Public-Private Partnerships To Achieve Global Access
Salimullah said achieving global access requires private-public partnerships to share risk and reward. Companies need to ask themselves if they can truly “go it alone,” or if they need to partner and leverage the scale of an organization to take CGTs to underserved patient populations. One such public-private partnership model Salimullah alluded to was Novartis’ partnership with the Bill And Melinda Gates Foundation to develop an in-vivo gene therapy to treat sickle cell disease (SCD) in sub-Saharan Africa.
With diseases like SCD, it’s important to understand epidemiology and to identify regions of prevalence. “Are you developing a therapy for the U.S. because you can potentially go to the open market or are you actually developing a therapy based on the epidemiology, which then will feed into your trials and understanding of the natural history of the disease?”
“One has to think systemically and not merely about getting therapy x to population y,” Hurlbut said. He argued it’s not as easy as scheduling a courier. It demands “thinking more expansively about the ways disease is a different kind of problem in different cultures and communities (for example, how SCD is viewed as witchcraft in some regions) and the ways in which government and governance comes into this picture.”
Lambert agreed that strategic planning and private-public partnerships are necessary to achieve global access, but said it also requires success in the U.S. and European markets — “and that is not a given by any means,” especially in Europe, she said, where it’s been difficult to successfully commercialize advanced therapies. “Getting it right and getting the economic base that’s necessary from the U.S. and Europe for these therapies is going to be absolutely essential to succeeding in global reach, and we have a lot of work left to do there.”