FDA rejects ITM radiopharmaceutical over manufacturing deficiencies

FDA declined to approve ITM Radiopharma's lutetium-177 edotreotide, known as ITM-11, for certain gastroenteropancreatic neuroendocrine tumors. The agency cited chemistry, manufacturing and controls deficiencies and issues involving a third-party commercial facility, according to ITM.

The complete response letter did not identify deficiencies in the submitted clinical efficacy or safety data, the company said. ITM plans to work with FDA and its manufacturing partners before resubmitting the application.

The application relied on the COMPETE study

ITM's filing included results from the phase 3 COMPETE trial, which compared ITM-11 with Novartis' Afinitor in patients with gastroenteropancreatic neuroendocrine tumors. The study showed an improvement in progression-free survival.

The trial did not show a statistically significant improvement in median overall survival. FDA's letter, as described by ITM, focused on manufacturing rather than requesting another efficacy study.

Radiopharmaceutical manufacturing has unusual constraints

Lutetium-177 products must be produced, tested and delivered within tightly controlled timeframes because the radioactive isotope decays. Commercial supply depends on coordination among isotope production, drug manufacturing, quality testing and treatment centers.

ITM is an established supplier of lutetium-177, including material used for Novartis' Pluvicto. The complete response letter shows that isotope experience does not remove the need to validate every facility and process supporting a new finished product.

The timing of a new review is not yet known

ITM has not said when it expects to complete corrective work or resubmit. FDA review timelines depend on the scope of the response and whether the agency classifies it as a shorter Class 1 review or a six-month Class 2 review.

Until the company provides a schedule, the launch remains delayed. ITM is continuing other studies of the drug in neuroendocrine tumors, including separate adult and pediatric programs.