Targeted Genetics restarts trial after woman's death

The U.S. Food and Drug Administration has allowed Targeted Genetics to restart its gene-therapy trial for rheumatoid arthritis after an investigation indicated the treatment did not contribute to the death of an Illinois woman in July.

The trial was put on hold when 36-year old Jolee Mohr died of a massive fungal infection weeks after being injected with the second dose of a treatment designed to fight arthritis by weakening the immune system in targeted areas.

A post-mortem analysis by University of Chicago researchers concluded that the Seattle-based company's drug didn't wildly spread through the patient's body, nor did it significantly increase the immune suppression produced by another anti-arthritis drug she was taking.

The FDA's decision clears some concern about the future of gene therapy, a field considered promising but risky. It also helps restore confidence in Target Genetics' clinical pipeline, which relies on gene-therapy products.

"This is very good for the company, for the product and for gene therapy," said Chief Executive H. Stewart Parker.

But Mohr's death also raised issues about whether patients with nonlethal diseases were being properly informed of the risks of medical experimentation before consenting to participate in clinical trials.

Targeted Genetics said that it was revising the "informed consent" document patients review before enrolling to include information about Mohr's death. The company is also amending the study's procedure to keep doctors from administering the drug to patients suffering from fever at the time scheduled for the injection. Mohr had a mild fever when she was injected with the treatment.

The study involves 127 patients, some 35 of whom are yet to receive a second dose of the treatment.

Over the next few weeks, Targeted Genetics will again seek consent from those patients and the approval of an independent ethics review board for the amended protocol.

"We'll certainly be up in the first quarter of the year," Parker said.

The company plans to start a follow-up, midstage clinical trial by mid- to late 2008.

Targeted Genetics' product relies on a tame virus — "adeno-associated virus," or AAV — to carry an immunosuppressant gene to selected areas of the body, such as the joints.

The gene helps block tumor necrosis factor-a, or TNFa, a protein that in excess amounts causes severe swelling and pain.

Targeted Genetics' therapy was being tested as a complement to other anti-TNFa drugs that didn't prove effective enough at reducing the symptoms of the disease in some patients.

It was feared that the injection of Targeted Genetics' product, in combination with the therapy Mohr was already taking, might have helped overwhelm the patient's immune system.

But molecular analysis of the patient's tissue found only traces of the AAV outside her joints, and the level of anti-TNFa blockage was typical of a patient taking general rheumatoid-arthritis treatments.

Histoplasmosis — the infection that killed Mohr — is a known side effect of some of these therapies, although most cases are mild.

A National Institutes of Health panel is scheduled to meet next month to discuss results of the investigation of Mohr's death.

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