The FDA has issued a CRL to the new drug application (NDA) seeking the approval of LNTH-2501, an investigational radioactive diagnostic kit intended for the preparation of gallium-68 edotreotide injection use with PET for the localization of somatostatin receptor (SSTR)–positive neuroendocrine tumors (NETs) in adult and pediatric patients.1
The FDA reported that it cannot approve the NDA due to third-party facility manufacturing-related conditions that were unresolved at the time of the NDA review. These facility inspection–related conditions must be resolved to a satisfactory level before an NDA for LNTH-2501may be approved, according to the FDA. Notably, the CRL did not cite any concerns about the data that supported the NDA. The CRL also did not note any issues related to the safety or efficacy of the diagnostic kit.
“We remain confident in LNTH-2501 and are committed to bringing this imaging agent to NETs patients and health care providers as soon as possible,” Mary Anne Heino, executive chairperson and chief executive officer of Lantheus, stated in a news release. “The feedback received from the FDA relates solely to our third-party manufacturer, and not to the clinical performance of the product. We are working closely with our partner and the agency to address these facility manufacturing-related conditions and advance the program.”
What data supported the NDA submission for LNTH-2501 in patients with SSTR-positive NETs?
The diagnostic accuracy of gallium-68 edotreotide in SSTR-positive NETs was demonstrated in 2 trials.2
FDA Issues CRL to LNTH-2501 for SSTR-positive NETs
- The FDA issued a CRL to the NDA seeking the approval of the LNTH-2501 kit for the preparation of gallium-68 edotreotide injection with PET for the localization of SSTR-positive NETs in adult and pediatric patients.
- The FDA reported that they cannot approve the NDA due to third-party facility manufacturing-related conditions that were unresolved at the time of the NDA review.
- The CRL did not cite any concerns about the data that supported the NDA.
The first phase 1/2 study (NCT01619865) compared gallium-68 edotreotide PET/CT with standard-of-care indium 111-pentetreotide (Octreoscan) SPECT combined with high-resolution, contrast-enhanced CT to determine its relative diagnostic performance.3 A total of 177 patients with known or suspected SSTR-positive NETs were enrolled.2
Results showed that gallium-68 edotreotide PET/CT demonstrated strong diagnostic concordance with reference standards. Reader 1 identified 121 true positive results and 39 true negative results, yielding positive and negative agreement rates of 91% (95% CI, 85%-95%) and 89% (95% CI, 75%-96%), respectively. Reader 2 produced similar findings, with 120 true positive results and 38 true negative results, corresponding to 90% (95% CI, 84%-95%) positive and 86% (95% CI, 73%-95%) negative agreement.
The second study, a phase 2 trial (NCT01869725), compared the diagnostic accuracy of gallium-68 edotreotide PET/CT with standard indium 111-pentetreotide imaging combined with contrast-enhanced CT or MRI in patients with SSTR–expressing tumors.4 All patients received intravenous gallium-68 edotreotide followed by PET/CT scanning. Within 120 days, they underwent standard indium 111-pentetreotide imaging with high-resolution, contrast-enhanced CT or MRI for diagnostic comparison. A second PET/CT scan was permitted within 3 to 6 months if initial findings required confirmation.
The study enrolled 62 patients with histologically confirmed NETs or other SSTR-positive tumors who were undergoing disease evaluation before or after treatment.2 Of these, 59 patients had sufficient data for efficacy assessment per the composite reference standard. Results demonstrated strong diagnostic agreement between gallium-68 edotreotide PET/CT and the reference standard, with positive and negative percent agreements of 92% and 75%, respectively, for reader 1, and 90% and 75% for reader 2.
What details are important to note about the potential clinical formulation and administration of LNTH-2501 in patients with SSTR-positive NETs?
LNTH-2501 would be supplied to radiopharmacies in the form of a kit containing 2 vials to allow for the direct preparation of gallium-68 edotreotide with Gallium eluate from an on-site generator at the radiopharmacy.1
References
- Lantheus receives complete response letter from FDA for LNTH-2501 (Ga 68 edotreotide). News release. Lantheus. June 26, 2026. Accessed June 29, 2026. https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-complete-response-letter-fda-lnth-2501-ga-68
- Prescribing information for GALLIUM Ga 68 EDOTREOTIDE§ INJECTION. US FDA. Updated July 2023. Accessed June 29, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210828s003lbl.pdf
- Safety of 68Ga-DOTA-tyr3-octreotide PET in diagnosis of solid tumors (GA-68). ClinicalTrials.gov. Updated July 27, 2021. Accessed June 29, 2026. https://clinicaltrials.gov/study/NCT01619865
- Comparative study of sensitivity of Ga-DOTATOC PET vs octreoscan SPECT + CT. ClinicalTrials.gov. Updated September 22, 2021. Accessed June 29, 2026. https://clinicaltrials.gov/study/NCT01869725
