- The Food and Drug Administration has lifted a clinical hold on UniQure's experimental hemophilia B gene therapy, clearing the way for the program to move forward. The drugmaker on Monday said the agency agrees with its conclusion that the treatment was unlikely to have caused a study volunteer's liver cancer.
- Working with an independent laboratory, the company analyzed a biopsy of the participant's tumor and determined there were no signs the gene therapy had triggered any genetic or biological changes likely to have contributed to the cancer.
- The clinical hold on UniQure's study was one of several setbacks in the gene therapy field in recent months. Resumption of the study following the company's investigation could help rebuild confidence around UniQure's research and the FDA's view of gene therapy trials.
Only one participant of the 54 enrolled in the HOPE-B trial of UniQure's gene therapy, called etranacogene dezaparvovec or etranadez, developed liver cancer. The volunteer had a history of hepatitis B and C infections — which many hemophilia patients contracted from receiving blood products before now standard clotting treatments were developed — and those infections are linked to 80% of liver cancer cases, UniQure said.
Trial investigators are monitoring participants with abdominal ultrasounds every six months to watch for any signs of cancerous growth. UniQure has treated nearly 100 patients with etranadez or other gene therapies for different inherited disorders, some as many as 10 years ago. The recent liver cancer case is the only one reported to date.
Following removal of the patient's tumor, samples were sent to independent analysts to test for signs that the adeno-associated virus vector UniQure uses to deliver a functional gene might have caused biological changes that later led to cancer.
UniQure said it found vector "integration" in only 0.027% of the cells in the tumor sample, and noted those integrations weren't clustered around genes linked to cancer. Genetic analysis of the tumor also found mutations that are characteristic of liver cancer development, independent of any treatment.
UniQure said it expects by the end of June to release data from the HOPE-B trial showing patient outcomes one year after infusion with etranadez. The company also expects to ask the FDA for the therapy's approval this year, although the agency has required longer follow-up data from another gene therapy company, BioMarin Pharmaceutical, for its hemophilia A gene therapy.
The FDA isn't the only U.S. regulator that UniQure needs to worry about. The company last year signed a global partnership with blood-products specialist CSL Behring, which is now under review from the Federal Trade Commission.
The FTC has sought additional information about the deal from the two parties. That agency is looking closely at biopharma transactions, and may be concerned about potential conflicts between etranadez and CSL's marketed clotting factor treatments for hemophilia B.
UniQure's shares rose by as much as 11% in morning trading on the news.