update
US FDA lifts clinical hold after Aduro modifies listeria-based therapy trials
Aduro was ordered to halt enrolment in all trials of its LADD-based (live, attenuated, double-deleted Listeria mononcytogenes) therapies in October.
The Food and Drug Administration’s (FDA) decision followed the detection of Listeria in a sample taken from the in-port of a medical implant worn by a participant in a Ph IIb trial of a LADD therapy called CRS-207.
While the patient showed no signs of systemic infection, the positive test raised concerns the modified bacteria can form biofilms on medical implants. A similar incident occurred in a separate trial conducted by Aduro last year.
Last night the California biotech announced the partial hold had been lifted.
The firm explained it had changed protocols for trials of its LADD therapies to extended patient surveillance, excluded subjects with certain prosthetic implants and added guidance on the administration of prophylactic antibiotics.
The Ph IIb trial - which is examining CRS-207 in combination with an anti-PD-1 compound for patients with mesothelioma - was already fully enrolled at the time of the partial clinical hold. It is expected to complete in the first half of 2017.
Auduro is developing CRS-207 in collaboration with Johnson & Johnson (J&J) unit Janssen Biotech, which licensed rights to a number of cancer drug candidates based on its novel LADD immunotherapy platform in 2014.
LADD technology
CRS-207, like Aduro’s therapeutic candidates, consists of a genetically modified version of the bacteria Listeria monocytogenes.
The organism has had genes required for replication replaced with those encoding protein antigens.
The idea is that while they can no longer replicate, the modified bugs can prompt the immune system to initiate a response to the specific target antigen.
Analyst comment
William Blair analyst John Sonnier said the lifting of the clinical hold is positive, suggesting the protocol modifications will reassure investors.
Sonnier also pointed out that both patients whose devices tested positive for listera recovered quickly and showed no signs of systemic infection
He adding that “we do not believe LADD-based therapies pose a significant risk at this time."
