The FDA has granted final approval for Bravnetsa (formerly PNT2003; lutetium Lu 177 dotatate), a bioequivalent and therapeutically equivalent radiopharmaceutical to Lutathera, as a treatment for adult patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to a news release from the developer, Lantheus Holdings, Inc.1
Moreover, the Lutathera bioequivalent was approved through the FDA’s Abbreviated New Drug Application (ANDA) pathway.2 As part of this review, Bravnetsa is the sole radiopharmaceutical determined to be bioequivalent and therapeutically equivalent to the reference product, Lutathera. Bravnetsa was granted tentative approval in March 2026 for the same population, but was subject to existing patent protections or exclusivity periods associated with Lutathera.3
“As the only radiopharmaceutical the FDA has determined to be bioequivalent and therapeutically equivalent to [Lutathera] approved in the US, [Bravnetsa’s] approval marks an important milestone for Lantheus as we continue to expand our radiopharmaceutical portfolio, bringing additional treatment options to [patients] living with GEP-NETs,” Mary Anne Heino, executive chairperson and chief executive officer of Lantheus, stated in the release.1 “We are focused on a thoughtful launch and ensuring the right commercial and operational capabilities are in place to support reliable supply and broad patient access.”
What data support the final approval?
The clinical efficacy supporting the initial approval of Lutathera in GEP-NETs was primarily established through the phase 3 NETTER-1 trial (NCT01578239), which compared the radiopharmaceutical plus octreotide (Sandostatin) against octreotide alone.4 In this study, the use of lutetium Lu 177 dotatate conferred a significant improvement in progression-free survival (PFS; HR, 0.21; 95% CI, 0.13-0.32). At the time of the primary analysis, the median PFS for the group receiving lutetium Lu 177 dotatate had not been reached, whereas the control group experienced a median PFS of 8.5 months.
Moreover, the median overall survival (OS) was 48.0 months (95% CI, 37.4-55.2) in the lutetium Lu 177 dotatate arm and 36.3 months (95% CI, 25.9-51.7) in the control arm. The HR for OS was 0.84 (95% CI, 0.60-1.17; P = .30).
Further evidence came from the ERASMUS Medical Center (MC) trial, a single-arm study involving 1214 patients. In the subset of 360 patients with GEP-NETs, the objective response rate (ORR) per RECIST v1.1 criteria was 16%. Moreover, 3 complete responses were observed in this subset of patients.
In the NETTER-1 trial, patients in the experimental arm received lutetium Lu 177 dotatate at a dose of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses. This was administered with long-acting octreotide at 30 mg given every 4 weeks. The control group received long-acting octreotide intramuscularly at a dose of 60 mg every 4 weeks.
A total of 229 patients with progressive SSTR–positive midgut NETs were enrolled in the NETTER-1 trial. All patients included in the study had tumors that were well differentiated and demonstrated SSTR expression on imaging.
The second study, the ERASMUS MC trial, was an open-label, single-arm, single-institution study conducted in the Netherlands. This trial assessed 1214 patients with SSTR–positive tumors who received lutetium Lu 177 dotatate at the same dose of 7.4 GBq at 200 mCi every 6 to 13 weeks for up to 4 doses. Within this larger cohort, 360 patients were identified as having GEP-NETs.
The primary end point for the NETTER-1 trial was PFS, as determined by a blinded independent radiology committee using RECIST v1.1 criteria. Secondary end points included ORR and safety. For the ERASMUS MC trial, the primary end points were ORR, PFS, and OSl.
In the NETTER-1 trial, the most common grade 3 or 4 adverse effects reported included lymphopenia (44%), increased γ-glutamyltransferase (20%), and vomiting (7%). Additionally, myelodysplastic syndrome events were reported in 2.7% of patients in the radiopharmaceutical arm.
References
- Lantheus receives final FDA approval for BRAVNETSA™ (Lutetium Lu 177 Dotatate), the only radiopharmaceutical FDA has determined to be bioequivalent and therapeutically equivalent to LUTATHERA® for the treatment of GEP-NETs. News release. Lantheus Holdings Inc. September 22, 2026. Accessed September 22, 2026. https://tinyurl.com/52s3rmwf
- 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 September 22, 2026. https://tinyurl.com/2p9jpcv6
- Lantheus receives FDA tentative approval for lutetium Lu 177 dotatate (PNT2003), radioequivalent to LUTATHERA. News release. Lantheus Holdings Inc. March 2, 2026. Accessed September 22, 2026. https://tinyurl.com/mryt82jx
- Strosberg JR, Caplin ME, Kunz PL, et al. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(12):1752-1763. doi:10.1016/S1470-2045(21)00572-6
