Jim Wilson warns Philly gene therapy conference of the ‘paradox’ that hurts investment

For years, gene therapy has been a high-tech engine of the Philadelphia-area economy. But lately, some investors have balked at fueling that engine with additional funds, one of its pioneers warned at an industry conference on Friday.

The reason? Gene therapies are designed to alleviate — even cure — genetic diseases with just one dose, University of Pennsylvania scientist Jim Wilson told a crowd of more than 300 at the Sheraton Valley Forge Hotel, in King of Prussia.

That’s a great achievement for science, but not so attractive for businesses — especially when the disease in question is rare, he said. There are few customers, and once treated, they don’t come back for more.

“It’s a paradox,” he said. “The interest in supporting this, especially for the rare diseases, is in decline.”

Wilson, director of Penn’s gene therapy program and a cofounder of several gene therapy start-ups, was a keynote speaker at the @Philly Cell and Gene Therapy Annual Conference.

He was followed by Peter Marks, a senior regulator at the FDA, who expanded on Wilson’s theme. Because gene therapies are administered just once, and because most of the patient populations are small, some companies have tried to recoup their costs by pricing treatments in the millions, Marks said. That approach isn’t sustainable, the FDA regulator said.

“I’m not going to throw stones at any of the current gene therapy companies,” he said. “But ultimately, if we’re going to move the field forward, we’re going to have to find a way to bring prices down by an order of magnitude.”

Wilson and Marks both proposed ways that costs of gene therapy might be reduced.

The Penn scientist described how his lab is working on next-generation vectors — inactivated viruses that are used to deliver beneficial genetic instructions into the bodies of people whose own genes are deficient. Newer vectors are more efficient at reaching the target organ in the patient’s body, he said, allowing for smaller doses. That means lower costs as well as fewer side effects.

No gene therapy scientist is more aware of the risk of side effects than Wilson. In 1999, a man named Jesse Gelsinger died after undergoing a gene therapy treatment that Wilson developed, setting the field back by years. (That treatment was delivered with a different type of virus that sometimes provoked harmful immune reactions. The vectors used today, called AAVs, are generally safe and well tolerated.)

Other possible ways for lowering costs include standardizing the molecular platforms and manufacturing techniques used to make the cutting-edge therapies, the FDA’s Marks said. That’s more efficient than starting from scratch with each new disease.

“We have to find a way to manufacture more efficiently,” he said.

The two-day conference was organized by the Sino-American Pharmaceutical Professionals Association of Greater Philadelphia. Friday morning began with an introduction from conference cochair Haichen Yang, a vice president at Philly-based Amicus Therapeutics.

Philadelphia’s prominence in cell and gene therapy has led some boosters to nickname the area Cellicon Valley, home to at least 55 companies in the field, by one estimate. But as Yang reminded attendees, the region has a long history of medical innovation, starting in 1751 with the founding of Pennsylvania Hospital, the nation’s first. Then in 1777 at Valley Forge, not far from the hotel where the conference was taking place, Gen. George Washington inoculated his troops against smallpox. It was one of the first such efforts to prevent infectious disease on a mass scale, Yang said.

Fast-forward to 2017, when the FDA approved the first of two gene therapies, both with Philly backstories. One was the leukemia treatment Kymriah, in which the patient’s defective immune cells are removed, modified, and reinfused — a process developed at Penn, known by the abbreviation CAR-T.

The other was Luxturna, in which corrective genes are injected directly into the eyes of patients with a rare hereditary form of blindness. One of the scientists who led that research, Katherine High, then at Children’s Hospital of Philadelphia, was scheduled to speak at the conference Saturday.

In addition to talking about lowering costs, Wilson described several of his recent research successes in laboratory animals, including a gene therapy that his lab tested on dogs with a debilitating metabolic disorder called Krabbe disease.

He played two short videos, the first showing how a dog with the disease was unable to use its hind legs, instead having to scoot on the floor. But in a second video, a dog that received an experimental gene therapy was able to run down a hallway, chasing after a bouncing red ball.

Then he went back to the issue of costs, projecting a slide full of headlines expressing skepticism about the gene therapy business model.

One cited a Goldman Sachs research report, asking: “Is curing patients a sustainable business model?”

Another was a headline about Passage Bio, a company that Wilson cofounded, and how it announced job cuts in 2022.

The answer, Wilson said, lay in more innovation. He closed his remarks by talking about “disruption” — a term more often used by innovators in Silicon Valley, not Cellicon.

“My final words to all of you are: Let’s be disruptive.”