The FDA has issued a Complete Response Letter for ITM-11, citing manufacturing and facility inspection issues but no clinical safety or efficacy concerns.

FDA raises CMC and facility issues

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for ITM Isotope Technologies Munich’s New Drug Application (NDA) for investigational radiopharmaceutical 177Lu-edotreotide, also known as ITM-11.

The CRL means the FDA cannot approve the application in its current form. According to ITM, the agency cited Chemistry, Manufacturing and Controls (CMC) issues and items related to inspections of a third-party commercial facility.

Importantly, the company said the FDA did not identify concerns relating to the clinical or nonclinical data package or the safety profile of ITM-11.

ITM said it is reviewing the FDA’s feedback with the relevant external parties and assessing the next steps. The company intends to resubmit the NDA.

ITM-11 is being developed for the treatment of gastroenteropancreatic neuroendocrine tumours (GEP-NETs), a group of cancers that can arise in the gastrointestinal tract and pancreas.

Andrew Cavey, chief executive officer of ITM, said: “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.”

Phase 3 trial met primary endpoint

The regulatory setback comes after positive results from the Phase 3 COMPETE trial, which compared 177Lu-edotreotide with everolimus in patients with inoperable, progressive Grade 1 or Grade 2 GEP-NETs.

The trial met its primary endpoint, with ITM reporting a statistically significant improvement in progression-free survival compared with everolimus.

COMPETE is registered as NCT03049189 and evaluated 177Lu-edotreotide in patients with advanced GEP-NETs.

The investigational treatment is a targeted radiotherapeutic designed to deliver radioactive lutetium-177 to tumour cells expressing somatostatin receptors.

The FDA’s CRL does not change the clinical results reported from COMPETE. However, ITM-11 remains an investigational product and has not been approved by a regulatory authority for any indication.

The company is also evaluating 177Lu-edotreotide in the Phase 3 COMPOSE study in patients with well-differentiated, aggressive Grade 2 or Grade 3, somatostatin receptor-positive GEP-NETs.

Manufacturing becomes next regulatory hurdle

The CRL highlights the importance of manufacturing and supply requirements in the development of radiopharmaceuticals, where commercial production and distribution involve complex facilities, quality controls and handling requirements.

ITM did not provide further details of the specific CMC deficiencies or the third-party facility inspection findings in its announcement.

The company said it will work with the FDA and relevant partners to address the outstanding issues before resubmitting the application.

The timing and scope of any potential resubmission remain unclear, meaning the CRL does not establish when ITM-11 could reach the market.

For patients and clinicians, the distinction between the regulatory issues and the clinical evidence will be important. The FDA has not identified new clinical safety or efficacy concerns in the application, but those positive clinical findings cannot by themselves support approval while the outstanding manufacturing and facility issues remain unresolved.

ITM said its goal remains to bring ITM-11 to patients with advanced GEP-NETs.