TgAAC94 exonerated in US trial death

PRLog (Press Release) – Nov 14, 2007 – Targeted Genetics (Boston, Massachusetts) says that final tests support earlier indications that a patient death during a trial of its injectable anti-arthritis drug, tgAAC94, was not caused by the drug. The company has submitted a package of data to the US Food and Drug Administration, which placed a hold on the trial in July. Targeted Genetics believes these data “thoroughly answer all of their questions and address all of the issues”, and hopes the FDA will release its hold on the trial before the end of 2007, a company spokesperson told Biopharm Development News.

The FDA has 30 days to respond to the company’s submission, so the hold could be lifted around the third week of November. However, it might decide to delay its decision until after the next meeting of the National Institutes of Health’s Recombinant DNA Advisory Committee, on December 3rd-4th. The Committee is undertaking a public review of trials involving adeno-associated virus vectors, including scientific and safety implications of the death in the tgAAC94 trial (see Biopharm Development News 24/9). Although the FDA’s decision is not connected to this public review, the Agency might consider it politic to await the imminent RAC findings, as the event was so public in nature.

Results of the investigation into the cause of the subject’s death, as well as positive interim data from the Phase I/II trial, were presented at the 71st annual meeting of the American College of Rheumatology, held in Boston, Massachusetts, on November 6th-11th.

Lead investigator Dr Philip J Mease, clinical professor at the University of Washington School of Medicine, reported data from 66 subjects who were given a questionnaire to report improvements in symptoms. A higher percentage of subjects who received tgAAC94 reported improvement in joint symptoms, function and pain compared with the placebo-injected group. The interim data also indicated that tgAAC94 is well-tolerated at doses up to 5x1013 DNase Resistant Particle. The most common adverse events noted were injection site reactions, seen in 10% of patients treated.

The results from the investigation into the patient death showed that no amplification of viral vector occurred in the patient’s body and that only trace amounts of vector DNA were detected in tissues outside the treated joint. “Results from the molecular tests indicate that tgAAC94 did not contribute to the patient’s death, which was due to disseminated histoplasmosis and a severe retroperitoneal hematoma,” said Dr Mease.

He also reported the following other factors exonerating tgAAC94:

Vector DNA was detected in the injected joint, as expected.
The other medications the subject was taking - adalimumab, methotrexate and prednisone - are known to be immunosuppressive and a risk factor for histoplasma infection.

There was no increase in TNF-α binding protein above what was expected based on the subject’s ongoing background adalimumab therapy.
There was no detectable TNFR:Fc protein in serum tested from all 16 other subjects who were not on any TNF-α antagonist therapy.

“The new data are very encouraging and we are hopeful we can resume this clinical trial soon,” said Targeted Genetics president and CEO H Stewart Parker. “Based on the clinical data generated and evaluated to date, we are now working with our advisory board to design the next phase of our clinical programme.” Article submitted by www.jobs4dd.com - for latest international news and jobs in the drug development and clinical research sectors.