Dive Brief:

• UniQure, the Belgian drug company leading the race to develop a gene therapy for hemophilia B, said Monday that testing of its treatment has been paused as researchers investigate an unexpected case of liver cancer in a participant in one of the company’s clinical trials.

• According to UniQure, the Food and Drug Administration placed a clinical hold on the program after a mid-December safety report showed a preliminary diagnosis of hepatocellular carcinoma in one patient who received the therapy, known as AMT-061, late last year, while enrolled in the pivotal HOPE-B study. UniQure noted the patient has multiple risk factors associated with HCC including a longstanding history of hepatitis B and C infections, evidence of non-alcoholic fatty liver disease and advanced age.

• UniQure CEO Matthew Kapusta said his company has administered AMT-061 to more than 100 patients over the last decade, with no reports of liver cancer until now. Yet, if researchers determine that the case is linked to AMT-061, it would be devastating for UniQure as well as other developers. Many of the gene therapies in development work like AMT-061, using so-called adeno-associated viruses to ship helpful genetic material into cells.

Dive Insight:

Today, nearly all large pharmaceutical companies — plus a growing number of small biotechs — have their hands in gene therapy. The technology always held the potential to treat a seemingly countless number of diseases tied to genetic malfunctions, and over the past couple decades, scientific advances turned that promise into reality. To date, the FDA has approved two gene therapies for inherited diseases, though the agency expects to be reviewing between 10 and 20 cell and gene therapies by 2025.

Yet, like most newer technologies, the excitement has been tempered by concerns, with one of the biggest being safety.

The gene therapy field suffered a major setback in the late 1990s, for example, after the high-profile death of a teenager who was given an experimental treatment for his rare liver disease.

Gene therapies also rely on certain viruses to shuttle genetic material into cells, a process that carries its own set of potential risks. Research indicates that some of these viruses, like gammaretroviruses and lentiviruses, can insert themselves into DNA near genes that can cause cancer. Four children in a French gene therapy study who were initially cured of a rare immune disorder many years ago later developed leukemia, for instance. One of them died in 2003.

Developers have hoped treatments made with adeno-associated viruses, or AAVs, would be a safer option, as the thinking goes it’s rare for these viruses to integrate with human DNA. Indeed, many of the gene therapies currently in development use a type of AAV — as do Roche’s Luxturna and Novartis’ Zolgensma, the two available in the U.S.

That theory could take a hit, though, if investigators find a link between AMT-061 and the cancer case seen in UniQure’s study.

“We’re taking this matter very seriously,” Kapusta said on a Monday morning call with investors, noting that, to UniQure’s knowledge, there have been no other reports of HCC in other AAV gene therapy studies.

Kapusta said the patient in question was dosed with AMT-061 in October 2019. Sometime before December of this year, an ultrasound detected a new liver lesion suspected of being HCC. UniQure notified the FDA of the situation in mid-December, which then led the regulator to halt the program last week.

A complete surgical resection of the lesion is scheduled for this week to confirm the HCC diagnosis and help determine any potential contribution from UniQure’s therapy. Kapusta said a full investigation is underway and should take one to three months to complete.

In spite of the investigation, UniQure still expects to submit AMT-061 for approval in the second half of 2021, following a meeting with the FDA early next year. The company noted that dosing is complete in each of its three hemophilia B gene therapy studies, and there are not plans to enroll or treat more patients.

“At this stage, we don’t know the etiology of this lesion,” Graham Foster, a professor of hepatology at Queen Mary University of London, said during UniQure’s Monday call. “I don’t for one moment want to suggest that there could not be an association with gene therapy. But I do want to put the risk in perspective.”

Earlier this year, UniQure sold off the rights to AMT-061 in the hemophilia B indication to CSL Behring for $450 million in cash. Kapusta said the only break clause in the deal is if antitrust regulators stand in the way — meaning CSL can’t pull out because of the clinical hold.

UniQure shares were trading at just under $37 Monday morning, reflecting a 20% decline from Friday’s close of market price. Roche and BioMarin Pharmaceutical, two more prominent companies trying to treat hemophilia with AAV gene therapy, also had stock dips of about 3% to 4%.