After discussion with the US Food and Drug Administration (FDA) a drug manufacturer has halted a gene therapy trial of a new experimental drug to treat inflammatory arthritis because a woman who was taking part in the trial has died. 28 other trials using the same type of gene therapy are also being investigated according to the Associated Press.
Jolee Mohr who was 36 years old, died at the University of Chicago Medical Center on 24th July, 22 days after having a second injection of the experimental drug tgAAC94, made by Targeted Genetics Corporation.
As a precautionary measure, the trial has stopped while an investigation is conducted into the cause of Jolee Mohr’s death. Some 100 participants already enrolled in the trail will continue to be followed and monitored, said the drug manufacturer.
According to a spokesman at the University of Chicago Medical Center, Jolee Mohr had liver and kidney failure when she arrived at the hospital. Samples of her tissue are being tested by various labs.
A lawyer representing Jolee Mohr’s husband, Robb Mohr, said they believe her death is connected to the trial.
According to the drug manufacturer, 127 patients have received an initial dose of either the active drug tgAAC94 or a placebo, and 74 have had a second dose of the active agent. The trial begain in October 2005.
H Stewart Parker, president and chief executive officer of Targeted Genetics said:
“Our primary concern remains that of the safety of the patients, and we are working diligently with the study’s Data Safety Monitoring Board and the FDA to determine the cause of this unexpected event as quickly as possible.”
The trial was a phase I/II study to assess the safety and potential efficacy of various doses of tgAAC94 injected directly into affected joints of patients with inflammatory arthritis.
The drug is an adeno-associated virus (AAV) vector that delivers a soluble form of a gene that codes for the TNFR:Fc protein, which inhibits the immune stimulating activity of tumor necrosis factor-alpha (TNF-alpha), a prime mediator of inflammation.
In March last year, the FDA gave the manufacturer the go ahead to include a higher dose group and increase the number of patients in the trial.
The 127 adults were randomized to three dosage groups to receive an injection of either tgAAC94 or placebo into either the knee, ankle, wrist, metacarpophalangeal or elbow. This would be followed by an open label injection of the drug after 12 to 30 weeks, depending on when symptoms of arthritis in the treated joint met the criteria for another injection.
According to the manufacturer, interim data on the trial suggests that the drug may lead to improvements in signs and symptoms of arthritis in injected joints.
The experimental drug tgAAC94 is designed to be a supplemental drug to help patients with inflammatory arthritis with one or more joints that are not responding fully to systemic protein therapy. Injecting it directly into the joints helps to stimulate secretion of TNFR:Fc within joint cells, reducing TNF -alpha activity in the joint, which potentially reduces inflammation and destruction of the joint.
The manufacturer said that their technology is based on AAV, a harmless and naturally occurring virus that has not been linked with any diseases in humans.
The FDA is not aware of any adverse effects of AAV in trials, but as a precaution it is reviewing all ongoing trials involving any use of AAV.
The Associated Press reports that the National Institutes of Health’s advisory committee on gene therapy is meeting next month to discuss the scientific implications of Jolee Mohr’s death.
Click here for manufacturer’s statement.
Written by: Catharine Paddock