FDA Marketing Authorizations: LUTATHERA, REMODULIN Impant – Drug and Device Digest

FDA BRIEF: Week of January 22, 2018


LUTATHERA (lutetium Lu 177 dotatate) injection

 Advanced Accelerator Applications

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


  •  First FDA Approval for a Peptide Receptor Radionuclide Therapy (PRRT) –  targeting molecule that carries radioactive component
  • Approved indication is a rare disease and unmet need in NET community

MECHANISM OF ACTION:  Binds to somatostatin receptors including malignant somatostatin receptor-positive tumors, and is internalized; beta emission from Lu 177 induces cellular damage


  • Randomized, multicenter, open-label, active-controlled trial, n=229, patients with progressive, well-differentiated, locally advanced/inoperable or metastatic somatostatin receptor-positive midgut carcinoid tumor, LUTATHERA vs. high-dose long-acting octreotides
  • Major efficacy outcome measure: Progression free survival (PFS); additional efficacy outcome measures were overall response rate (ORR), duration of response, overall survival (OS), RECIST criteria


  • Median PFS was not reached for LUTATHERA vs. 8.5 mo. in octreotide (p<0.0001)
  • Efficacy in subset (n=360) of 1214 patients with GEP-NET tumors;  16% ORR  including 3 complete responses


  • Adverse Reactions:  Lymphopenia, increased GGT, vomiting, nausea, elevated AST,  increased ALT, hyperglycemia, hypokalemia
  • Myelodysplastic syndrome reported


  • Priority review, Orphan Drug Designation
  • Postmarketing Requirements: Safety analyses based on 5 and 10 yr followups, Overall Survival data
  • Complete Response Letter and Discipline Review Letter issued previously requesting additional data


  • Expanded Access Program
  • NETSPOT, another FDA-approved Molecular Nuclear Medicine from Advanced Accelerator,  granted Transitional Pass-Through status under “A-code” (A9587) for drug reimbursement
    • HCPCS “A Code” will be used on claims to private payers
  • However, UK medicines cost-effectiveness group, NICE, has published draft guidance not recommending LUTATHERA




INDICATIONS FOR USE:  For adult patients with Class I, II and III pulmonary arterial hypertension (PAH) receiving intravenous delivery of Remodulin.

Physicians prescribing this system for use with Remodulin must be familiar with the indications, contraindications, warnings, precautions, adverse events, and dosage and administration information described in the Remodulin drug labeling.

The Model 8551 Refill Kit is intended for use in refilling the Medtronic implantable  programmable infusion pumps with the exception of Medtronic MiniMed infusion pumps.


Consists of the following components:

  • Medtronic SynchroMed II 8637P Programmable Pump (the “pump”)
  • Medtronic 8201 Implantable Intravascular Catheter (the “catheter”)
  • Medtronic N’Vision 8840 Clinician Programmer with 8870 Application Card (the  “programmer”)
  • Remodulin (treprostinil) Injection stored in pump reservoir and, per a programmed prescription, moves through pump tubing, catheter port, and catheter to  intravascular delivery site
  • Programmer is handheld device for healthcare provider use only that is used to review and program pump parameters using telemetry, a radio frequency communication


  • Multi-center, prospective, single arm, non-randomized open label Investigational Device Exemption (IDE) clinical study, n=64, met the approved Remodulin indication, using approved concentrations, and approved intravenous route
  • Primary endpoint: Demonstrate safety when used with the Medtronic SynchroMed II Implantable Infusion System to deliver Remodulin
  • No effectiveness endpoint – effectiveness based on ability to provide accurate drug delivery
  • Clinical data, mathematical modeling, bench testing indicate that over the expected longevity of the pump, the accuracy ratio will decrease and plateau at ~ 0.8
  •  Primary safety objective met (p<0.0001); catheter revisions, early pump  replacement rates significantly less than literature reports


  • Device Generic Names: Pump, Infusion, Implanted, Programmable
    Implantable Intravascular Catheter, Clinician Programmer
  • Device Procode: LKK
  • Postmarketing requirements: Report on  pump failure analysis, validate the initial training program utilizing the to-be-marketed user interface, PAS reports


  • Existing codes and coverage for infusion pumps and associated parts
  • Information specific to this device not available


Image credit:  Advanced Accelerator Applications, Medtronic

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