Manufacturing issues mar ITM's radiopharma filing, says FDA
Dr Andrew Cavey, ITM's chief executive.
ITM's first attempt to score FDA approval for one of its radiopharma therapies has been knocked back by the agency.
The US regulator has sent a complete response letter (CRL) to Germany-based ITM, saying there are deficiencies in its chemistry, manufacturing and controls (CMC) in its New Drug Application (NDA) for ITM-11 (177Lu-edotreotide), a somatostatin receptor-targeting therapy for gastroenteropancreatic neuroendocrine tumours (GEP-NETs).
GEP-NETS are a rare group of complex cancers that start in the nerve cells and hormone-producing cells of the gastrointestinal tract and pancreas, and are often asymptomatic and slow-growing.
In particular, the CRL refers to issues related to inspections at a third-party commercial manufacturing site, and ITM said the FDA has not identified any problems with its clinical safety and efficacy results with ITM-11, or asked for any additional data.
"Our confidence in ITM-11's therapeutic potential has not wavered, and we are committed to working closely with the FDA and our partners to address the items outlined in the CRL," said Dr Andrew Cavey, ITM's chief executive.
"Our pivotal COMPETE trial data package stands, and our goal remains unchanged as we work toward bringing ITM-11 to patients living with advanced GEP-NETs," he added, noting that the company is working towards resubmitting the marketing application as soon as possible.
COMPETE compared the efficacy of ITM-11 to Novartis' targeted drug Afinitor (everolimus) in patients with inoperable, progressive Grade 1 or Grade 2 GEP-NETs and was published in The Lancet journal in July.
Median progression-free survival (PFS) was significantly longer with the radiopharma therapy – coming in at 23.9 months versus 14.1 months in the control group – and the objective response rate (ORR) was 22% and 4%, respectively.
The improvement in PFS did not translate into a statistically significant improvement in overall survival (OS). Nevertheless, there has been a lot of anticipation for ITM-11 among oncologists caring for GEP-NET patients, as a substantial proportion of patients enrolled in COMPETE had pancreatic tumours (P-NETs), a type which has limited treatment options.
If it does get approval, ITM-11 would compete with Novartis' somatostatin receptor-directed Lutathera (177Lu-dotatate), offering dosing every three months rather than two with the current drug.
ITM-11 received an orphan designation from the FDA as a treatment for GEP-NETs based on the data from a phase 2 clinical study, and is also being tested in lung and thymus NETs and other somatostatin receptor-positive cancers.
You can hear a recent interview with Dr Andrew Cavey, carried out by our web editor Nicole Raleigh, here.
