FDA Accepts Abbreviated NDA for 177Lu-PNT2003 in SSTR+ GEP-NETs

If approved by the FDA, it is possible that 177Lu-PNT2003 will become available for 180 days of marketing exclusivity in the United States.

The FDA has accepted an abbreviated new drug application (ANDA) for Lutetium Lu 177 Dotatate (177Lu-PNT2003), a generic formulation of lutetium Lu 177 dotatate (Lutathera) for patients diagnosed with somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) including foregut, midgut, and hindgut NETs, according to a press release from Lantheus Holdings.¹

It is believed that the application is the first to be considered a substantially completed ANDA for lutetium Lu 177 dotatate containing a Paragraph IV certification under the provisions of the Hatch-Waxman Act.² Following approval from the FDA, it is possible that 177Lu-PNT2003 will become available for 180 days of marketing exclusivity in the United States.

177Lu-PNT2003 is a SSTR–targeted radioligand agent that is being created for those diagnosed with SSTR-positive NETs.³ Somatostatin analogs were created with anti-secretory and anti-proliferative mechanisms, with randomized clinical trials yielding efficacious findings with the class of drug.

The FDA approved lutetium Lu 177 dotatate for the treatment of GEP-NETs—including in the foregut, midgut, and hindgut—in January 2018.⁴ The approval was supported by data from the phase 3 NETTER-1 trial (NCT01578239). In the study, patients were randomly assigned 1:1 to be treated with either lutetium Lu 177 dotatate at 7.4 GBq every 8 weeks for up to 4 administrations at a maximum cumulative dose of 29.6 GBq and 30 mg of long-acting octreotide via intramuscular injection every 4 weeks, or 60 mg of octreotide every 4 weeks.

The median progression-free survival (PFS) was not reached in the lutetium Lu 177 dotatate cohort compared with 8.5 months in the high-dose, long-acting octreotide cohort (HR, 0.21; 95% CI, 0.13-0.32).

The agent was also assessed in a population of 360 of 1214 patients with GEP-NETs who were assessed via RECIST criteria as part of the ERASMUS Medical Center study. Lutetium Lu 177 dotatate, which was administered at a dose of 7.4 GBq every 6 to 13 weeks for a maximum of 4 doses resulted in an overall response rate (ORR) of 16%. Moreover, investigators reported 3 complete responses.

The primary end point of the NETTER-1 trial was PFS based on RECIST v1.1 criteria. Secondary end points included ORR, overall survival, time to tumor progression, duration of response, quality of life, and adverse effects (AEs).

Patients 18 years and older with metastatic or locally advanced inoperable midgut carcinoid tumors and progressive disease based on RECIST v1.1 guidelines were able to enroll on the trial. Additional eligibility criteria included having a Karnofsky performance status of at least 60 and 1 or more measurable sites of disease.

Several frequent grade 3/4 AEs were reported among patients in the experimental arm of the phase 3 NETTER-1 trial vs the control arm, including lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea (5%), elevated aspartate aminotransferase (5%), increased alanine transaminase (4%), hyperglycemia (4%), and hypokalemia (4%). Additionally, myelodysplastic syndrome was observed in 2.7% of patients who were treated with lutetium Lu 177 dotatate and long-acting octreotide compared with no patients in the control arm.

References

1. Lantheus announces acceptance of its first-to-file ANDA for generic LUTATHERA® (Lutetium Lu 177 Dotatate). News release. Lantheus Holdings. January 11, 2024. Accessed January 12, 2024. https://yhoo.it/3TSxTp7
2. FDA. Patent certifications and suitability petitions. January 10, 2024. Accessed January 12, 2024. https://bit.ly/3SeaIV4
3. Point Biopharma. Pipeline. Accessed January 12, 2024. https://bit.ly/3HeLwHN
4. FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS. News release. FDA. January 26, 2018. Accessed January 12, 2024. https://bit.ly/4aR8aDB