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
ADDRESSING UNMET NEED:
- 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
EFFICACY:
- 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
SAFETY:
- Adverse Reactions: Lymphopenia, increased GGT, vomiting, nausea, elevated AST, increased ALT, hyperglycemia, hypokalemia
- Myelodysplastic syndrome reported
REGULATORY PATHWAY: NDA
- 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
ACCESS & REIMBURSEMENT:
- 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- However, UK medicines cost-effectiveness group, NICE, has published draft guidance not recommending LUTATHERA
IMPLANTABLE SYSTEM for REMODULIN
Medtronic
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.
DEVICE DESCRIPTION:
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
EFFECTIVENESS & SAFETY:
- 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
REGULATORY PATHWAY: PMA
- 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
REIMBURSEMENT
- Existing codes and coverage for infusion pumps and associated parts
- Information specific to this device not available