Drug Alert – FDA Approval – lutetium Lu 177 dotatate injection, for intravenous use ( LUTATHERA ®)

RJH – Drug Alert

FDA Drug Approval – lutetium Lu 177 dotatate ( LUTATHERA ®)

Generic Name Brand Name Manufacturer Approval Date Anticipated Availability Accelerated Review
lutetium Lu 177 dotatate Lutathera Advanced Accelerator Applications USA. Inc. 1/26/2018 Not available Priority Review with Orphan Drug Designation

Labeled Indication:

Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Drug Class:

Comparative Drugs in Class:

Peptide Receptor Radionuclide Therapy (PRRT) None – Innovator

Mechanism of Action:

Lutetium Lu 177 dotatate is a radiolabeled somatostatin analog which binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells.

Clinical Trial Summary:


A randomized, multicenter, open-label, active-controlled trial in 229 patients with progressive, somatostatin receptor-positive midgut carcinoid tumors were randomized (1:1).  Arms included LUTATHERA 7.4 GBq (200 mCi) administered every 8 to 16 weeks with long-acting octreotide (30mg after each Lutathera dose and every 4 weeks), or high-dose octreotide (60mg every 4 weeks).  Significant results (p-value<0.0001) were reported for reduction in risk of disease progression or death and progression free survival.



Results are based on data from an international, single-institution, single-arm, open-label trial of 1,214 patients with somatostatin receptor-positive tumors.  LUTATHERA was initially provided as expanded access under a general peptide receptor radionuclide therapy protocol at a single site in the Netherlands.  A retrospective medical record review was conducted on a subset of patients.  The investigator assessed (objective response rate) ORR was 16% (95% CI 13, 20) in the 360 patients with GEP-NETs.

Warnings and Adverse Effects (AE):


Risk from Radiation Exposure


Secondary Myelodysplastic Syndrome and Leukemia

Renal Toxicity


Neuroendocrine Hormonal Crisis

Embryo-Fetal Toxicity

Risk of Infertility



Adverse effects most observed in clinical trials include nausea (65%), vomiting (53%), fatigue (38%), abdominal pain (26%), diarrhea (26%), decreased appetite (21%), headache (17%), dizziness (17%), peripheral edema (16%), flushing (14%), back pain (13%), anxiety (12%), renal failure* (12%), alopecia (12%), hypertension (12%), pain in extremity (11%) and cough (11%).  For a complete list see the product labeling.  Abnormal lab values were observed in the hematologic, renal/metabolic and hepatic panels with the most common Grade 3-4 adverse reactions reported as lymphopenia (44%), increased GGT (20%), vomiting (7%), nausea (5%), elevated AST (5%), increased ALT (4%), hyperglycemia (4%), and hypokalemia (4%)

*Includes the terms: Glomerular filtration rate decreased, acute kidney injury, acute prerenal failure, azotemia, renal disorder, renal failure, renal impairment



The following rates of serious adverse reactions were reported per the ERASMUS trial safety data: myelodysplastic syndrome (2%), acute leukemia (1%), renal failure (2%), hypotension (1%), cardiac failure (2%), myocardial infarction (1%), and neuroendocrine hormonal crisis (1%)

NDC Strength Volume Single Dose Vial (SDV) Storage
69488-0003-01 370 MBq/mL (10 mCi/ml) 20.5 ml in a type I glass 30 mL vial SDV Below 25 °C (77 °F)

Vial is in a lead shielded container placed in a plastic sealed container

69488-0003-70       Shipped in a Type A package

Drug Sales Forecast (in millions):

2018(F) 2019(F) 2020(F) 2021(F) 2022(F) 2023(F)
Global 107 229 362 455 522 580


FDA press release https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594043.htm?utm_campaign=01262018_PR_FDA%20approves%20new%20treatment%20for%20digestive%20cancers&utm_medium=email&utm_source=Eloqua (Accessed 02/05/2018)

Product Labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208700s000lbl.pdf  (Accessed 02/05/2018)

Pharmaceutical Company press release https://www.novartis.com/news/media-releases/advanced-accelerator-applications-receives-fda-approval-lutatherar-treatment-gastroenteropancreatic-neuroendocrine-tumors (Accessed 02/05/2018)

RJ Health Web Site (Accessed 02/05/2018)

Pharma Intelligence Web Site (Accessed 02/05/2018)

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