FDA Approval Sought for Another Formulation of Lutetium Lu 177 Dotatate in SSTR+ GEP-NETs

Curium has submitted a 505(b)(2) new drug application (NDA) to the FDA, seeking the approval of the company’s formulation of lutetium Lu 177 dotatate injection for the treatment of patients with somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETS).¹

Lutetium Lu 177 dotatate (Lutathera), which is a product from Advanced Accelerator Applications, a Novartis company, was approved by the FDA in January 2018 for the treatment of adult patients with SSTR-positive GEP-NETs, including foregut, midgut, and hindgut neuroendocrine tumors in adults.2 The indication was expanded to include pediatric patients 12 years of age and older in April 2024.³

In the company’s announcement, Curium said it has been developing its formulation of lutetium Lu 177 dotatate for several years and has ensured its product does not infringe on any Orange Book patents.¹

“Curium’s 505(b)(2) NDA for lutetium Lu 177 dotatate injection marks another important milestone for Curium in its evolution to bring new tools for patients and health care providers to both diagnose and now potentially treat disease,” Michael Patterson, chief executive officer of Curium North America, stated in a news release. “Nuclear medicine-based cancer therapies must continue to be more widely and reliably available for patients and their caregivers.”

A 505(b)(2) NDA is used when 1 or more of the investigations cited by the applicant to support approval were not conducted by or for the applicant, and if the applicant has not acquired a right of reference or use for the investigations. For this type of NDA, the FDA is allowed to rely on data from a source other than the application, including published literature or the regulatory agency’s findings for safety and/or efficacy, of a previously approved drug.⁴

The initial 2018 approval of lutetium Lu 177 dotatate for adult patients with SSTR-positive GEP-NETs was supported by data from phase 3 NETTER-1 trial (NCT01578239). The pediatric approval in 2024 was also based on efficacy data from NETTER-1, as well as pharmacokinetic, dosimetry, and safety data from the phase 2 NETTER-P trial (NCT04711135).^2,3

Findings from NETTER-1 showed that patients treated with lutetium Lu 177 dotatate (n = 116) experienced a median progression-free survival (PFS) that was not reached vs 8.4 months (95% CI, 5.8-9.1) for those treated with high-dose long-acting octreotide (n = 113; HR, 0.21; 95% CI, 0.13-0.33; P < .001).5 The estimated 20-month PFS rates were 65.2% (95% CI, 50.0%-76.8%) for lutetium Lu 177 dotatate vs 10.8% (95% CI, 3.5%-23.0%) for octreotide.

The international, multicenter NETTER-1 trial enrolled adult patients with histologically confirmed and centrally verified, locally advanced or metastatic, inoperable midgut neuroendocrine tumors who experienced disease progression per RECIST 1.1 criteria over a maximum of 3 years during treatment with octreotide. Patients needed to have well-differentiated tumors and somatostatin receptors present on all target lesions.

Patients were randomly assigned 1:1 to receive lutetium Lu 177 dotatate at 7.4 GBq (200 mCi) every 8 weeks for up to 4 total doses with a maximum cumulative dose of 29.6 GBq in combination with long-acting octreotide at 30 mg once every 4 weeks; or high-dose long-acting octreotide alone at 60 mg once every 4 weeks.²

Blinded independent radiology committee–assessed PFS per RECIST 1.1 criteria served as the trial’s primary end point.

Regarding safety, the most common grade 3/4 adverse effects (AEs) reported in at least 4% of patients treated with lutetium Lu 177 dotatate plus long-acting octreotide were lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea (5%), increased aspartate aminotransferase (5%), increased alanine aminotransferase (4%), hyperglycemia (4%), and hypokalemia (4%).

NETTER-P featured 9 pediatric patients who were treated with lutetium Lu 177 dotatate, including 4 patients with GEP-NETs. Safety data showed that the AE profile of the agent was similar in pediatric patients compared with its known safety profile in adults.³

References

1. Curium submits new drug application for lutetium Lu 177 dotatate injection. News release. Curium. July 9, 2024. Accessed July 10, 2024. https://www.curiumpharma.com/2024/07/09/lutetium-lu-177-dotatate-injection/
2. FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS. FDA. January 26, 2018. Accessed July 10, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-dotatate-treatment-gep-nets
3. FDA approves lutetium Lu 177 dotatate for pediatric patients 12 years and older with GEP-NETS. FDA. April 23, 2024. Accessed July 10, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-dotatate-pediatric-patients-12-years-and-older-gep-nets
4. Engaging with the FDA during new drug development. FDA. Accessed July 10, 2024. https://www.accessdata.fda.gov/cder/sb-navigate/material/glossary.pdf
5. Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427