Lutetium Lu 177 Dotatate Radioequivalent Receives Tentative FDA Approval for SSTR+ GEP-NETs

The FDA has granted tentative approval for the abbreviated new drug application (ANDA) for PNT2003—a lutetium lu 177 dotatate (Lutathera) radioequivalent—for the treatment of patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors.¹

PNT2003 is an SSTR-targeted radioligand therapy composed of no-carrier-added lutetium-177 (¹⁷⁷Lu).² SSTRs represent well-established therapeutic targets in NETs, and somatostatin analogs have long been used in NET management because of their antisecretory and antiproliferative activity, with clinical trial data demonstrating their clinical efficacy in this disease. PNT2003 is currently under phase 3 investigation. Lutathera received initial approval in 2018 and is currently indicated for the treatment of adult and pediatric patients 12 years and older with SSTR-positive GEP-NETs, including foregut, midgut, and hindgut neuroendocrine tumors.³

The FDA’s tentative approval of the ANDA for PNT2003 indicates that the agency has completed its review and determined that the application meets the requirements for approval.¹ However, full approval is contingent on the expiration of the 30-month regulatory stay, which is expected in June 2026.

“As the first radioequivalent to Lutathera to receive FDA tentative approval, PNT2003 marks an important step forward in Lantheus’ work to advance treatment options for patients with GEP-NETs. This milestone comes at a time when advances in imaging and evolving clinical guidelines are enabling the identification of more patients who stand to benefit from targeted radiopharmaceutical therapies. As the leading radiopharmaceutical-focused company, we remain committed to meeting this growing demand and look forward to making PNT2003 available to patients pending final FDA approval,” Mary Anne Heino, chief executive officer of Lantheus Holdings, Inc, stated in a news release.

What is the regulatory history of PNT2003?

In November 2022, Lantheus and POINT Biopharma announced several collaboration agreements, granting Lantheus worldwide exclusive licensing rights to POINT’s investigational agents PNT2002 and PNT2003.² Under the agreement, POINT was responsible for leading completion of the ongoing University Health Network–sponsored OZM-067 trial (NCT02743741) in Canada, while Lantheus managed regulatory submissions in the United States.

In January 2024, Lantheus announced that the FDA had accepted the ANDA filing for PNT2003 in its current indication.⁴

What was the design of OZM-067?

The prospective, single-arm, multicenter trial evaluated the safety and efficacy of PNT2003 in 195 patients with SSTR-positive NETs identified by gallium-68 dotatate PET imaging.^5,6

Patients were required to have radiographic evidence of disease progression within 6 months before enrollment, an ECOG performance status of 2 or less, a Ki-67 index of 30% or less, and adequate laboratory and hepatic function within 2 weeks prior to study entry.⁶ Patients with extensive bone metastases involving more than 25% bone marrow were also eligible, provided hematologic reserve was carefully monitored.

Eligible patients received 4 cycles of therapy. The primary end point was progression-free survival (PFS) at 12 months from the last dose of treatment.⁵

What results has OZM-067 reported?

Results from a quality-of-life (QOL) analysis, presented at the 2024 American Society of Clinical Oncology Annual Meeting, showed that patients with primary site–agnostic gallium-68 dotatate PET–positive NETs experienced improvements in multiple QOL domains, including symptoms, following treatment with PNT2003. At a median follow-up of 33 months (range, 3-71), the reported 12-month PFS and overall survival rates were 81% (95% CI, 75%-86%) and 92% (95% CI, 87%-95%), respectively.

References

1. Lantheus receives FDA tentative approval for Lutetium Lu 177 Dotatate (PNT2003), radioequivalent to Lutathera. News release. Lantheus Holdings, Inc. March 2, 2026. Accessed March 2, 2026. https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-fda-tentative-approval-lutetium-lu-177
2. Lantheus and POINT Biopharma announce strategic collaboration and exclusive license agreements for the commercialization of PNT2002 & PNT2003. News release. Lantheus Holdings, Inc. November 14, 2022. Accessed March 2, 2026. https://www.globenewswire.com/news-release/2022/11/14/2554779/0/en/Lantheus-and-POINT-Biopharma-Announce-Strategic-Collaboration-and-Exclusive-License-Agreements-for-the-Commercialization-of-PNT2002-PNT2003.html
3. Lutathera. Prescribing information. Novartis; 2024. Accessed March 2, 2026. https://www.novartis.com/us-en/sites/novartis_us/files/lutathera.pdf
4. Lantheus announces acceptance of its first-to-file ANDA for generic Lutathera (lutetium Lu 177 dotatate). News release. Lantheus Holdings, Inc. January 11, 2024. Accessed March 2, 2026. https://www.globenewswire.com/news-release/2024/01/11/2807869/0/en/Lantheus-Announces-Acceptance-of-its-First-to-File-ANDA-for-Generic-LUTATHERA-Lutetium-Lu-177-Dotatate.html
5. Wong RKS, Myrehaug S, Juergens RA, et al. Quality of life (QoL) benefits following ¹⁷⁷Lu-DOTATATE therapy in patients (pts) with ⁶⁸Ga-DOTATATE PET positive primary site agnostic neuroendocrine tumors (NET). J Clin Oncol. 2024;42(suppl 16):e16291. doi:10.1200/JCO.2024.42.16_suppl.e16291
6. Lu-dotatate treatment in patients with 68Ga-dotatate somatostatin receptor positive neuroendocrine tumors. ClinicalTrials.gov. Updated December 3, 2025. Accessed March 2, 2026. https://clinicaltrials.gov/study/NCT02743741