Researcher says Targeted Genetics drug not to blame in death

Recent tests run by University of Chicago scientists points to the innocence of Targeted Genetics' gene therapy for inflammatory arthritis in last summer's death of an Illinois woman in a clinical trial, one of the university researchers said.

The results suggest that the Seattle-based company's experimental therapy didn't greatly amplify the immune suppresion of a commercial arthritis drug the patient was already taking. A breakdown of 36-year-old Jolee Mohr's immune system led to the massive fungal infection that killed her in July.

There's "no real 'smoking gun' here," said Dr. Kyle Hogarth, the University of Chicago Medical Center doctor who treated Mohr at the intensive-care unit where she died.

Mohr died three weeks after being injected in the knee with Targeted Genetics' experimental therapy, which relies on a tame virus to carry an immuno-suppresant gene that reduces inflamation in arthritis-ridden joints.

An analysis of Mohr's tissue indicates that the virus — known as an adeno-associated virus, or AAV — was barely detectable outside of the joints, dispelling the suspicion that it might have contributed to the generalized immune system failure that allowed the fungus to spread, according to Hogarth.

The patient's immune system was already compromised by another arthritis drug — Humira — which operates on a similar principle, but whose effects are more spread throughout the body.

Both Targeted Genetics' compound and Humira — manufactured by Abbott Laboratories and approved by the Food and Drug Administration — seek to block Tumor Necrosis Factor-a, or TNFa, a protein that signals the immune system where to attack an infection, but that in excess amounts causes severe swelling and pain. Anti-TNFa treatments are known to cause fungal infections, but they are usually mild.

The level of anti-TNFa blockage in Mohr's blood "was no higher than would be expected for someone on Humira," Hogarth said in an e-mail.

He added that concerns about the design of the Targeted Genetics trial are still valid. Testing one TNFa blocker while allowing people to remain on another "is just bad science," he said.

Targeted Genetics spokeswoman Stacie Byars said that commercially available TNFa blockers do not fully resolve inflammation in 40 percent of patients, and the trial was designed to complement the action of those therapies with a locally injected version.

"If the local injected drug is not known to leave the action site, and therefore does not contribute to systemic side effects, then why does it matter if someone is on TNF blockers already?" she said

The University of Chicago findings could benefit Targeted Genetics, which has had its most important clinical trial put on hold in the wake of Mohr's death. The results also may lift hopes for the field of gene therapy, considered promising by many scientists but overshadowed by the 1999 death of Jesse Gelsinger at a clinical trial in Pennsylvania and more recently by the Mohr case.

A National Institutes of Health panel that met in September to discuss Mohr's death refrained from clearing gene therapy from any role in the patient's death. But data presented there pointed in that direction, said Dr. Mark Kay, a gene therapy expert at Stanford University.

"This just confirms it even more," he said.

Dr. Philip Mease, chief of rheumatology clinical research at the Swedish Medical Center and lead investigator for the Targeted Genetics clinical trial, said in an interview that the independent data monitoring committee for the study had concluded that the company's compound "had nothing to do with her reason for death."

Mease is scheduled to make a presentation on the Targeted Genetics therapy on Saturday afternoon at a scientific meeting in Boston.

Another NIH panel is scheduled to meet in early December to discuss the complete data. The FDA has yet to decide whether the Targeted Genetics clinical trial can be resumed.

Ángel González: 206-515-5644 or agonzalez@seattletimes.com