Two decades after a patient died in his gene-therapy trial, Penn’s Jim Wilson has a new approach — to be tested in babies

More than two decades after a patient with liver disease died in his gene-therapy trial, University of Pennsylvania scientist Jim Wilson has a new approach for tackling the same disease, this time in babies.

On Wednesday, a biotech start-up that plans to test the drug announced $65 million in venture capital funding, a mark of how far the controversial Penn scientist has come since the 1999 death of 18-year-old Jesse Gelsinger.

The concept remains the same: Inject patients with genetic instructions to make a crucial liver enzyme that they are unable to make themselves.

Gelsinger had a mild form of the disease, called OTC deficiency, but babies with a severe form of the illness can lapse into a coma within a day or two of birth, their brains damaged by a buildup of ammonia. Some die soon thereafter; the rest have little recourse beyond a liver transplant.

Yet when Gelsinger was injected with the corrective gene, packaged inside a virus, his immune system unexpectedly rebelled, and he died within a week.

In Wilson’s new approach, the gene is delivered with a different type of virus that does not trigger the immune system — a delivery method that he already has licensed for use in several other drugs. Among them is Zolgensma, an FDA-approved, one-shot treatment for a fatal childhood disease called spinal muscle atrophy.

“These diseases are tragic,” he said. “We think we can really make a difference.”

The new gene therapy for OTC deficiency is being tested by iECURE, a Plymouth Meeting-based start-up that Wilson cofounded in 2020. Wilson, who serves as iECURE’s chief scientific adviser, also owns a stake in the venture, as does Penn.

After securing the go-ahead from the FDA, the plan is to treat a small group of infants by the end of 2023, chief executive officer Joseph Truitt said. Based on Wilson’s preliminary studies in his lab at Penn, the agency already has designated the treatment as an orphan drug — which qualifies for tax incentives because it is designed to treat a rare disease.

The bulk of the new $65 million investment will go toward testing the treatment for OTC deficiency, though some will be used to develop treatments for two other liver diseases, Truitt said.

The funding is especially significant given that venture capitalists lately have been lukewarm on the biotech sector, said Supriya Munshaw, a faculty member at Johns Hopkins Carey Business School who studies investment in the life sciences.

“It’s a good vote of confidence that they were able to raise this much money in the current market,” she said. “There’s lots of hesitation in gene and cell therapies, which specifically have cooled down over the last few years.”

The financing was led by the venture capital firms Novo Holdings A/S and LYFE Capital, with “significant participation” from Versant Ventures and OrbiMed Advisors, which previously funded iECURE with an initial $50 million.

As part of the deal, OrbiMed partner Tal Zaks, a former senior executive at the COVID-19 vaccine maker Moderna, gets a seat on iECURE’s board. iECURE is in the process of doubling its 12-member staff and moving into new offices in Blue Bell.

In the years since Gelsinger’s death, Wilson’s search for better solutions established him as a gene-therapy pioneer in the eyes of his peers. But lately he has come under fire in a different context.

Earlier this year, former employees accused him of fostering a toxic, abusive environment in his lab at Penn, according to an investigation by STAT, a health sciences news site. A university investigation confirmed some of the allegations but concluded that Wilson was not at fault.

Asked about the accusations this week, Wilson said he and other lab leaders have vowed to address any employee concerns.

“We regret that people felt that way, but we are proud of the way the organization has responded and very, very committed to making sure the experience for employees is as great as it can be under challenging times,” he said.

In addition to using a safer virus than what Gelsinger received, Wilson’s new approach for treating OTC deficiency differs in how the genetic instructions reside inside the patient’s liver cells.

In the original approach, the corrective gene was not incorporated into the patient’s genome. That meant any time the person made more liver cells, the beneficial genetic code would not get copied into the new cells, and over time, the treatment would be watered down.

In the new treatment to be tested by iECURE, the replacement gene will be inserted into the patient’s DNA — an ideal approach for babies because of their fast-growing livers, Wilson said. The treatment will keep pace as they grow.

If the path of other gene-therapy drugs is any guide, the treatment likely would be priced in the many hundreds of thousands of dollars, said Munshaw, the Hopkins researcher.

Gene-therapy manufacturers have defended these high prices by noting the drugs are generally one-shot treatments, and potentially are less expensive than a lifetime of periodic treatments with less effective drugs. Some insurers have responded by negotiating alternative payment models, such as paying in installments as long as the therapy continues to work, she said.