Experimental gene therapy trial for arthritis allowed to resume

Nov 27 2007

Trials in the U.S. of a controversial and experimental gene therapy have been given the green light to resume following the tragic death of a volunteer in July.

The trial conducted by Targeted Genetics using gene therapy tgACC94 for inflammatory arthritis was halted after the death of Jolee Mohr.

Mohr who became ill shortly after receiving the treatment, died from a fungal infection that spread rapidly throughout her body.

At the time she was taking the immune system-suppressing drug Humira and the fungal infection histoplasmosis is a known side effect of the drug.

It is suspected that the gene therapy suppressed her immune system and then exaggerated the Humira-related problems.

Investigations conducted by the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) reviewed the safety data on all 127 subjects in the trial and all data from the fatality and reached the conclusion that the gene therapy did not cause the woman's death.

Mohr was recruited for the trial by her own arthritis doctor who delivered the treatment and there have been criticisms that the dual nature of his role may have compromised his objectivity.

Critics also suggest that Targeted Genetics failed to clearly state the protocols to guide doctors in administering the therapy and reporting possible adverse events.

Mohr apparently received the final shot when she was unwell which was a mistake as the therapy is designed to suppress the immune system.

The FDA only became aware of Mohr's problems two weeks later, when her system had already failed; she died five days later.

Experts were confused at the time as to whether Mohr's problems were because of her immune system-suppressing gene therapy or her immune system-suppressing drugs and they have criticised Targeted Genetics and Mohr's doctor for a lack of caution and for conducting early-stage research in such a potentially confusing and careless manner.

Targeted Genetics however says a Phase I trial of tgAAC94 in patients who were not on anti-TNF systemic therapy encountered no safety problems and on that basis authorization was granted for the Phase I/II trial.

Targeted Genetics says patients in this trial can be, but do not have to be, on concomitant anti-TNF therapies and the scientific premise of the research is that the drug will provide symptomatic relief and improved outcomes for such a group of patients.

When Targeted Genetics first sought approval to test tgAAC94 in people, the FDA approved a single dose in patients who were not taking other drugs but were dubious about approving multiple shots or testing it in people taking other arthritis medications.

Experts have also questioned whether early-stage gene therapy trials should be conducted at all on people whose condition, like Mohr's, was not severe.