Patient’s death prompts US FDA to review AAV trials

PRLog (Press Release) – Aug 10, 2007 – The US FDA is reviewing ongoing trials involving adeno-associated virus vectors (AAVs) as a precaution following the death of a patient during a trial of Targeted Genetics’ injectable anti-arthritis drug, tgAAC94.  The company informed the FDA of the patient’s death on July 24th, just days after the agency had placed the trial on hold following notification of a serious adverse event relating to the same patient (see earlier report).

The agency said that the investigation into the cause of the patient's illness and subsequent death was “intensive and ongoing”.  However, it is not aware of similar adverse events occurring in other gene therapy trials, either with tgAAC94 or with drugs using other genes in AAV vectors.  It is working with the National Institutes of Health to assess potential scientific and safety implications of the event, which are to be discussed at the September meeting of the NIH Recombinant DNA Advisory Committee.

Responding to a critical article about its development programme in the Washington Post (August 6th), Targeted Genetics provided a detailed chronology of the patient’s path through the trial and the company’s adverse event reporting, as follows:
•   In February, 2007, the patient was enrolled in the trial and received the first dose of tgAAC94, followed by a second dose on July 2nd.
•   On July 10th, the clinical investigator reported to Targeted Genetics that two patients had nausea, fever and vomiting.  As this is not uncommon, the symptoms were simply recorded as adverse events (AEs) believed to be unrelated to the study drug.  However, in line with regulatory procedures and the study protocol, they were noted for inclusion in the study's annual report to the FDA.
•   On July 13th, Targeted Genetics was notified that the patient had been hospitalised, which is considered a serious adverse event (SAE).  The investigator said that the SAE was unlikely to be related to tgAAC94, so the event was again simply noted for the annual report.  The other patient's symptoms had resolved.
•   On July 17th, the investigator notified the company that the patient's condition was deteriorating, but reiterated that the SAE was unrelated to the study drug.  Targeted Genetics notified the chairman of its independent data safety monitoring board (DSMB) about the situation on July 18th followed by the full DSMB on July 19th.
•   “After a comprehensive analysis in concert with the DSMB, due to the temporal relationship between dosing and the onset of the event, the company decided to report the SAE to the FDA as possibly related to the study drug.  Although FDA requirements are that SAEs possibly related to study drug must be reported within a week, the company held a teleconference on July 20th with the FDA and the clinical investigator involved in this case, within 24 hours of making the determination that the SAE was possibly related to drug.  The trial was officially put on hold and all study sites were notified.  The official IND safety report was filed on July 23rd.”
Results of the study are due to be presented at the American College of Rheumatology annual scientific meeting in Boston, Massachusetts in November 2007. Article submitted by Jobs4 Drug Development Ltd – www.jobs4dd.com