Carlsbad, CA—Durhane Wong-Rieger, PhD, president and CEO of the Canadian Organization for Rare Diseases and chair of a global alliance for patient organizations called Rare Diseases International, recalled a recent conference where he found himself speaking between panels with a patient advocate from Zimbabwe.

The woman, whom Wong-Rieger regards as one of the smartest and most involved patient advocates he knows, told him she would not go to any more sessions on cell and gene therapy because she didn’t want to hear about therapies that she or her patients would never get.

Wong-Rieger immediately realized the truth in her statement: many people who are in dire health conditions have no access to what may be a life-saving treatment.

“We really don’t have any rules for [cell and gene therapies] as we’re all saying this is the most amazing breakthrough in terms of therapies—truly lifesaving therapies,” said Wong-Rieger. “But the problem is we can’t give them to everybody. Unfortunately for us in this whole space, how do we get to doing what is the right thing?”

While Wong-Rieger doesn’t have the answer, he thinks that evolving ethics are at the heart of what will allow the field of cell and gene therapy get there.

A North Star

Ethics often gets a bad rap for being prohibitive, but for J. Benjamin Hurlbut, PhD, associate professor, School of Life Sciences, Arizona State University, that’s just plain wrong. Hurlbut believes that ethics is primarily about innovation and limits themselves can be sources of creativity and innovation.

“This is a domain where lives are at stake, and it makes this industry a different kind of industry than other industries because the stakes associated with the work, how the work is done, what the work means, and the name of the public goods the work has undertaken have a greater significance than in the automobile and smartphone industries,” said Hurlbut.

Tim Hunt, JD, CEO of the Alliance for Regenerative Medicine (ARM), has been mulling over the ethics of cell and gene therapy for months because, ultimately, this is the business of permanently altering people’s DNA or irreversibly transplanting cells.

“For too many of our patients—millions of people around the world—the status quo represents death or serious disability,” said Hunt. “No one runs out and takes gene therapy, a gene editing regimen, or cell therapy because they feel great and healthy. Patients are in difficult shape.”

Rob Perez, operating partner at the global growth equity firm General Atlantic, feels similarly about ethics, which he defines as a set of moral principles that helps one navigate challenging problems and situations.

“If we can have more conversations and come to more alignment on what an ethical code or ethical standards could be for the industry, it can help to be a north star on how we want to operate and how we want to make those very difficult decisions,” said Perez. “That’s always been a really important part of how I can deal with the most challenging questions, the most challenging decisions, and the most challenging complexities in operating a business.”

Value and accessibility

While the goal of many cell and gene therapies is to cure diseases and completely return a patient to full health, an incremental change in the patient’s health, which also can greatly affect a whole family, is understated. Somebody having to walk or sit for the rest of their time can be incredible in terms of that benefit.

Tay Salimullah, vice president, Global Head of Value and Access, Novartis Gene Therapies, was part of the team that led the first FDA-approved cell therapy, Kymriah, and is currently on a team working on a treatment for spinal muscular atrophy. He says defining patient success happens before one even begins to define value and economics.

“You have to actually understand the journey—the days, weeks, months, years—it takes families to try and get care,” said Salimullah. “It’s like a diagnostic odyssey where they can’t even actually then find out who’s going to treat them in what center. And that’s before even getting to the transaction of buying a gene therapy!”

For Salimullah, it’s all about democratizing access to gene therapies. Salimullah thinks carefully about how polarizing cell and gene therapy can be, especially regarding pricing.

“How can you have a $2-million gene therapy and leave babies to die?” asked Salimullah.

He believes in a self-imposed responsibility that looks for ways to find new opportunities where patients worldwide get access not only in the United States but in Europe and other environments. Salimullah thinks that the theme of democratizing access is dependent on finding the right people who can reinvent a playbook. But who is going to set that up? Will anyone take responsibility and apply it globally?

Janet Lambert, former CEO of ARM and now a consultant at The Densmore Group, believes the global democratization of cell and gene therapies will rely on public-private partnerships. That is a steep hill to climb.

“We’ve had such trouble successfully commercializing advanced therapies, and it is my view that 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,” she said. “And we have a lot of work left to do there.”

The failed system of responsibility                             

Hurlbut thinks that it’s important to address whether the way of doing innovation in health for the public good is suited to the kind of innovation that is happening in cell and gene therapy. If it isn’t going to serve people as well as it can, then it’s no good.

“All the different stakeholders engage with the sector to ask pretty hard questions about whether the way business as usual is playing out is the best way for that business to play out,” said Hurlbut. “And if things change, some businesses may get broken. But that’s the way things should go if the question is about the broader purpose of this domain, which is to heal people, to treat people.”

According to Hurlbut, an obvious issue to address is pricing, because the sticker shock is so profound that it’s easy for people to protest such steep prices and blast the entire industry of cell and gene therapy as useless.

As he is not a health economist, Hurlbut doesn’t claim to have the answer. However, he said if the regimen is unsustainable for the long run such that society cannot benefit from the good things that its investments have produced, then it’s a failure. Hurlbut said that thinking about these kinds of questions—such as whether cell and gene therapy is economically sustainable—has ethical stakes.

“Is the right way to ask questions about that life in terms of healthcare costs saved, future economic productivity, or to count the various beings and pile them up and say, look, there’s value here?” said Hurlbut. “Maybe that’s the way that one has to convince some set of actors, but maybe that’s the wrong way to ask questions about children’s lives.”

Hurlbut goes one step further, suggesting that, depending on a particular society or government, the decision on whether to get treated or not could be taken completely out of the hands of the patient at the earliest of life stages, even before birth, for all sorts of reasons like cost-savings—the more people who are “cured,” the less of an economic burden on that society. Hurlbut brings up a situation for which he has unique insight—that of He Jankui and the IVF embryos that he gene-edited—noting that one of the central arguments for this infamous experiment that was undertaken in China a few years ago is that it’s a lot easier and a lot cheaper to do it in one cell than to do it in many.

Hurlbut thinks that thinking through this ethical problem highlights that with the system that gets put in place—the drug makers, the regulators, the insurance companies, the health systems—no singular actor is responsible, but instead, it’s the collective actions of the community put in place—and that’s where things can go wrong because it results in failures of responsibility, compassion, and recognition of what is at stake.

After all, there is a dark side to gene therapy, and not every company working on cell or gene therapy is thinking about how their technology may contribute to applications that they would never endorse and, even, abhor, such as genetic cleansing.

Changing the path of humanity 

Even in a world where accessibility and economics for cell and gene therapies get worked out ethically, there’s another set of questions lying in wait that are top of mind for Lambert. For example, if a person chooses to get treated with gene therapy and it reaches the germline, genetic changes will be made in the patient and possibly in their children and generations to come.

Similarly, who is responsible for whether a child with a disease will get gene therapy? Does it fall into the hands of the parents?

“One of the most profound conversations I had in my time at ARM was with a mom who had signed her child up for a safety study,” said Lambert. “And even though this was a very well-educated mom, she felt profound guilt about having done that and that her child was, therefore, ineligible to get a therapeutic dose, which in that particular case turned out to be different than the safety trial dose.”

When it comes to gene editing, Lambert thinks that a major challenge in deciding what is a disease, what’s worth preventing, and what needs to be prevented.

At the end of the day, cell and gene therapy is not about eliminating or customizing people—it’s about treating patients.

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