`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208700Orig1s000
`
`MULTI-DISCIPLINE REVIEW
`Summary Review
`Office Director
`Cross Discipline Team Leader Review
`Clinical Review
`Non-Clinical Review
`Statistical Review
`Clinical Pharmacology Review
`
`

`

`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`Food and Drug Administration
`Center for Drug Evaluation and Research
`
`Memorandum
`
`FROM: Steven Lemery, M.D., M.H.S.
`Associate Director
`Division of Oncology Products 2
`Office of Hematology and Oncology Products
`Office of New Drugs
`Center for Drug Evaluation and Research
`
`SUBJECT: Addendum to Review, NDA 208700
`
`Applicant: Advanced Accelerator Applications
`
`On January 18, 2018, FDA and AAA held a telephone conference to discuss the appropriate
`administration recommendations for Lutathera. The primary concerns regarding the method of
`administration of Lutathera would be to administering health care staff as long as the intravenous
`line is intact and the instructions regarding “do not administer as a bolus” are followed [the risk
`of bolus administration may also be most pertinent to health care staff administering Lutathera
`due to manipulations that would be required to prepare the bolus].
`
`
`The FDA review team suggested to AAA during the review of the NDA that the product should
`be diluted and then hung. After further consideration, based on the applicant’s justification, this
`procedure (to dilute), would increase the risk of radiation exposure to staff. The proposed
`procedure without dilution leaves the Lutathera vial in the lead container or behind appropriate
`shielding during the entirety of the infusion. Conversely, shielding a 500 mL bag may be a
`challenge to health care providers. Furthermore, AAA stated that they have no studies supporting
`the proposed dilution and that manipulation risks sterility failure.
`
`AAA also stated that they have experience administering Lutathera safely during the NETTER-1
`trial in more than 35 centers in the US and the EU. Lutathera has been administered to over
`1,000 patients in the clinical development program and Lutathera stated during the call that they
`have not reported serious adverse events related to the procedure during the development
`program.
`
`A review of the ADAE dataset for NETTER-1 was conducted to assess potential adverse events
`related to the procedure (e.g., in the SOCs General Disorders and Administration Site Conditions
`and Injury, Poisoning and Procedural Complications). There was one instance of extravasation
`
`Reference ID: 4212057
`
`(b) (4)
`
`

`

`reported (verbatim term of right arm IV infiltration); however, the event was Grade 1 in severity
`and the patient recovered (infiltration can occur, however, irrespective of method for infusion).
`Other reports of injection site reaction or pain were included in the dataset; however, these
`occurred across both arms and the majority appeared related to IM injections of long-acting
`octreotide (which were administered in both arms). Grade 3 or greater events appeared unrelated
`to the infusion of Lutathera (e.g., pneumothorax during pacemaker insertion, SMV stent device
`occlusion, and G-tube malfunction). Review of SAEs from the Erasmus study did not appear to
`show any serious adverse events related to the administration of Lutathera (this reviewer
`acknowledges; however, that medication errors could have occurred without a report in the
`adverse event datasets if the patient was not affected).
`
`Prior to the call, an internal meeting was held (see t-con memo) with review staff from DMEPA,
`ONDQA, DOP2, and DMIP. DMIP (with prior consultation with their radiopharmacist) agreed
`that the proposed procedure would be a safer procedure compared with the suggested method for
`dilution (and that the product should remain in the vial prior to administration). Although the
`administration procedure is unique, radiopharmaceuticals have a limited distribution and are only
`administered by physicians/centers that have met the requirements for an NRC license.
`Furthermore, there are a limited number of radiopharmaceuticals approved for the treatment of
`cancer. These products have different radioisotopes and different administration/storage
`considerations. DMIP stated that it is common for drug companies to submit brochures to the
`radiopharmacist (i.e., outside of the label). AAA has developed educational pieces intended to
`assist staff in the safe administration of the product. As stated above, these educational pieces
`will primarily be directed at the safety of the health care provider (and that these health care
`providers are limited to specially trained staff qualified in the safe handling and administration of
`radiopharmaceutical products).
`
`During the call, DOP2 and DMEPA agreed that Section 2.5 of product labeling should be revised
`to provide more specific (and clear) instructions regarding the administration procedure.
`Educational pieces could then be drafted that are consistent with final agreed upon labeling.
`
`Reference ID: 4212057
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`STEVEN J LEMERY
`01/25/2018
`
`Reference ID: 4212057
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`NDA/BLA Multi-Disciplinary Review and Evaluation
`Application Type New Drug Application/New Molecular Entity
`Application Number(s) 208700
`Priority or Standard Priority review
`Submit Date(s)
`July 24, 2017 (resubmission)
`Received Date(s)
`July 26, 2017
`PDUFA Goal Date
`January 26, 2018
`Division/Office Division of Oncology Products 2/OHOP
`Review Completion Date
`
`Established Name Lutetium Lu 177 Dotatate
`(Proposed) Trade Name LUTATHERA
`Pharmacologic Class Radiolabeled somatostatin analog
`Code name None
`Applicant Advanced Accelerator Applications USA, Inc. (AAA)
`Formulation(s)
`Intravenous
`Dosing Regimen 7.4 GBq every 8 weeks for four doses
`Applicant Proposed
`Treatment of adult patients with somatostatin receptor positive
`Indication(s)/Population(s)
`gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
`including foregut, midgut and hindgut, neuroendocrine tumors
`Recommendation on
`Regulatory Action Approval
`Recommended
`For the treatment of somatostatin receptor positive GEP-NETs
`Indication(s)/Population(s)
`including foregut, midgut, and hindgut neuroendocrine tumors in
`(if applicable)
`adults
`
`1
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`
`Table of Contents
`
`Reviewers of Multi-Disciplinary Review and Evaluation ................................................................ 9
`
`Additional Reviewers of Application ............................................................................................... 9
`
`Glossary ......................................................................................................................................... 10
`
`1. Executive Summary ............................................................................................................... 12
` Product Introduction ...................................................................................................... 12
` Conclusions on the Substantial Evidence of Effectiveness ............................................ 12
` Benefit-Risk Assessment ................................................................................................ 13
` Patient Experience Data ................................................................................................. 21
`
`2. Therapeutic Context .............................................................................................................. 23
`
`2.1 Analysis of Condition ............................................................................................................. 23
`2.2
`Analysis of Current Treatment Options ......................................................................... 24
`
`3. Regulatory Background ......................................................................................................... 26
`3.1 U.S. Regulatory Actions and Marketing History ............................................................. 26
`3.2
`Summary of Presubmission/Submission Regulatory Activity ........................................ 26
`
`4. Significant Issues from Other Review Disciplines Pertinent to Clinical Conclusions on
`Efficacy and Safety................................................................................................................. 29
`4.1 Office of Scientific Investigations (OSI) .......................................................................... 29
`4.2
`Product Quality .............................................................................................................. 29
`4.3
`Clinical Microbiology ...................................................................................................... 29
`4.4 Devices and Companion Diagnostic Issues .................................................................... 29
`
`5. Nonclinical Pharmacology/Toxicology................................................................................... 30
`5.1
`Executive Summary ........................................................................................................ 30
`5.2
`Referenced NDAs, BLAs, DMFs ....................................................................................... 31
`5.3
`Pharmacology ................................................................................................................. 31
`5.4
`ADME/PK ........................................................................................................................ 37
`5.5
`Toxicology ....................................................................................................................... 39
`5.5.1 General Toxicology .................................................................................................. 39
`5.5.2 Genetic Toxicology .................................................................................................. 40
`5.5.3 Carcinogenicity ........................................................................................................ 40
`
`2
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`5.5.4 Reproductive and Developmental Toxicology ........................................................ 40
`5.5.5 Other Toxicology Studies ........................................................................................ 40
`
`6. Clinical Pharmacology ............................................................................................................ 41
`6.1
`Executive Summary ........................................................................................................ 41
`6.2
`Recommendations ......................................................................................................... 41
`6.3
`Postmarketing Requirements and Commitments ......................................................... 42
`6.4
`Summary of Clinical Pharmacology Assessment ............................................................ 42
`6.5
`Pharmacology and Clinical Pharmacokinetics ................................................................ 43
`6.6 General Dosing and Therapeutic Individualization ........................................................ 43
`6.6.1 General Dosing ........................................................................................................ 43
`6.6.2 Therapeutic Individualization ................................................................................. 44
`6.6.3 Outstanding Issues .................................................................................................. 44
`6.6.4 Summary of Labeling Recommendations ............................................................... 44
`Comprehensive Clinical Pharmacology Review ............................................................. 45
`6.7.1 General Pharmacology and Pharmacokinetic Characteristics ................................ 45
`Clinical Pharmacology Questions ................................................................................... 47
`6.8.1 To what extent does the available clinical pharmacology information provide
`pivotal or supportive evidence of effectiveness? ............................................................. 47
`6.8.2 Is the proposed dosing regimen appropriate for the general patient population for
`which the indication is being sought? .............................................................................. 48
`6.8.3 Is an alternative dosing regimen or management strategy required for
`subpopulations based on intrinsic patient factors? ......................................................... 48
`6.8.4 Are there clinically relevant food-drug or drug-drug interactions, and what is the
`appropriate management strategy? ................................................................................. 51
`
`6.7
`
`6.8
`
`7. Sources of Clinical Data and Review Strategy ....................................................................... 52
`7.1
`Table of Clinical Studies .................................................................................................. 52
`7.2
`Review Strategy .............................................................................................................. 54
`
`8. Statistical and Clinical and Evaluation ................................................................................... 56
`8.1
`Review of Relevant Individual Trials Used to Support Efficacy ...................................... 56
`8.1.1 NETTER-1 (AAA-III-01; NCT01578239) Trial Design ................................................ 56
`8.1.2 NETTER-1 Trial Study Results .................................................................................. 70
`8.1.3 Erasmus Medical Center (EMC) Clinical Trial (MEC127.545/1993/84) ................... 90
`8.1.4 Assessment of Efficacy Across Trials ..................................................................... 110
`
`3
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`8.2
`Review of Safety ........................................................................................................... 113
`8.2.1 Safety Review Approach ....................................................................................... 113
`8.2.2 Review of the Safety Database ............................................................................. 115
`8.2.3 Adequacy of Applicant’s Clinical Safety Assessments .......................................... 119
`8.2.4 Safety Results ........................................................................................................ 120
`8.2.5 Analysis of Submission-Specific Safety Issues ....................................................... 129
`8.2.6 Clinical Outcome Assessment (COA) Analyses Informing Safety/Tolerability ...... 137
`8.2.7 Safety Analyses by Demographic Subgroups ........................................................ 138
`8.2.8 Specific Safety Studies/Clinical Trials .................................................................... 138
`8.2.9 Additional Safety Explorations .............................................................................. 138
`8.2.10
`Safety in the Postmarket Setting ................................................................... 139
`8.2.11
`Integrated Assessment of Safety ................................................................... 140
`
`SUMMARY AND CONCLUSIONS .................................................................................................. 140
`8.3
`Statistical Issues ........................................................................................................... 140
`8.4
`Conclusions and Recommendations ............................................................................ 141
`
`9. Advisory Committee Meeting and Other External Consultations ....................................... 146
`
`10. Pediatrics ............................................................................................................................. 147
`
`11. Labeling Recommendations ................................................................................................ 148
`11.1
`Prescription Drug Labeling ....................................................................................... 148
`
`12. Risk Evaluation and Mitigation Strategies (REMS) .............................................................. 152
`
`13. Postmarketing Requirements and Commitment ................................................................ 153
`
`14. Division Director (DHOT) ..................................................................................................... 155
`
`15. Division Director (OCP) ........................................................................................................ 156
`
`16. Division Director (OB) .......................................................................................................... 157
`
`17. Division Director (Clinical) ................................................................................................... 158
`
`18. Office Director (or designated signatory authority) ............................................................ 160
`
`19. Appendices .......................................................................................................................... 161
`19.1
`References ................................................................................................................ 161
`
`4
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`19.2
`Financial Disclosure .................................................................................................. 163
`19.3
`Nonclinical Pharmacology/Toxicology...................................................................... 163
`19.4
`OCP Appendices (Technical documents supporting OCP recommendations) ......... 164
`19.5
`Additional Clinical Outcome Assessment Analyses .................................................. 164
`19.5.1 MedDRA Adverse Event Diagnosis (MAED) Tool Analysis ............................. 164
`19.5.2
`Analysis of Patient Reported Outcomes ........................................................ 169
`
`
`
`5
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`
`Table of Tables
`
`
`Table 1: Summary of FDA Approved Treatments for GEP-NETS .................................................. 25
`Table 2: IC50s (nM) For Displacement of Somatostatin ................................................................ 32
`Table 3: Binding Activity of Somatostatin Analog Constructs ..................................................... 32
`Table 4: Summary of Internalization and Retention of Radiolabeled Compounds in AR42J Cells33
`Table 5: Biodistribution of [177Lu]-DOTA-Y3-Octreotate in CA20948 Tumor Bearing Lewis Rats
`....................................................................................................................................................... 33
`Table 6: Listing of Clinical Trials Relevant to this NDA .................................................................. 53
`Table 7: Modification of Amino Acid Infusion Rate for Nausea and Vomiting During Infusion ... 60
`Table 8: Visit Schedule: 177Lu-DOTA0-Tyr3-Octreotate Treatment Arm .................................... 61
`Table 9: Visit Schedule: Octreotide LAR (Octreotide) Treatment Arm ......................................... 63
`Table 10: NETTER-1 Trial: OS Analysis Timing and 2-Sided Stopping Boundary for OS on the ITT
`....................................................................................................................................................... 66
`Table 11: NETTER-1 Trial: Actual Censoring Rule for Priamry PFS Analysis .................................. 67
`Table 12: NETTER-1 Trial: Disposition by Treatment on the ITT .................................................. 72
`Table 13: NETTER-1 Trial: Overview of Major Protocol Deviations .............................................. 73
`Table 14: NETTER-1 Trial: Demographic Characteristics of Patients in the ITT Population ......... 74
`Table 15: NETTER-1 Trial: Disease Characteristics of Patients in the ITT Population ................... 76
`Table 16: NETTER-1 Trial: Prior Treatment for Midgut Carcinoid in Patients on the ITT ............. 77
`Table 17: NETTER-1 Trial: Distribution of Stratification Factors in the ITT Population ................ 78
`Table 18: NETTER-1 Trial: Neuroendocrine Tumor Markers at Baseline in the ITT Population ... 79
`Table 19: NETTER-1 Trial: Applicant’s PFS Analyses, Per IRC assessment .................................... 80
`Table 20: NETTER-1 Trial: Time from randomization to tumor assessment date as per IRC tumor
`assessment .................................................................................................................................... 81
`Table 21: NETTER-1 Trial: Time from treatment start to tumor assessment date as per IRC tumor
`assessment .................................................................................................................................... 81
`Table 22: NETTER-1 Trial: FDA’s PFS Analyses, Per IRC assessment ............................................. 83
`Table 23: NETTER-1 Trial: ORR Results Based on the IRC Measurements .................................... 84
`Table 24: NETTER-1 Trial: OS Analyses (CSR) ................................................................................ 85
`Table 25: NETTER-1 Trial: Updated OS Analyses in the ITT without Imputed Date ..................... 86
`Table 26: NETTER-1 Trial: Global Health Status QLQ changes from baseline between both
`treatment Arms............................................................................................................................. 88
`Table 27: NETTER-1 Trial: FDA’s PFS Subgroup Analyses ............................................................. 88
`Table 28: ERASMUS: Study Assessments ...................................................................................... 95
`Table 29: ERASMUS: Demographic Characteristics of the FAS and SAF Analyses Sets .............. 103
`Table 30: ERASMUS: Disease Characteristics ............................................................................. 105
`Table 31: ERASMUS: Overall Response Rate (ORR) and Duration of Response (DoR) for Overall
`Study Population (SAF) and Selected Subgroups........................................................................ 107
`Table 32: Response Rate Following Treatment with 177Lu-DOTA0-Tyr3-Octreotate in Patients
`with Progressive Midgut Carcinoid Tumors. Comparison Between Findings in the NETTER-01
`and EMC Study Subsets .............................................................................................................. 110
`Table 33: Key Differences between design of NETTER and EMC................................................ 111
`
`6
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`Table 34: NETTER-1: Cumulative Lutathera Exposure (GBq/mCi) in the Safety Population (n=111)
`..................................................................................................................................................... 116
`Table 35: NETTER-1: Distribution of Lutathera Administrations in the Safety Population (N=111)
`..................................................................................................................................................... 116
`Table 36: Cumulative Lutathera Exposure (GBq/mCi) in the Safety Population: Comparison of
`ERASMUS and NETTER-1 ............................................................................................................. 117
`Table 37: ERASMUS: Cumulative Lutathera Exposure (GBq/mCi) in Patients Treated at Doses in
`Excess of 29. 6GBq (800 mCi) (n=216) ........................................................................................ 117
`Table 38: Key Demographic and Disease Characteristics Which Differ Between the NETTER-1
`and ERASMUS Trials .................................................................................................................... 118
`Table 39: NETTER-1: Per-patient Incidence of Serious Adverse Events Occurring More
`Frequently in Lutathera Treated Patient with an Incidence of ≥ 2% .......................................... 122
`Table 40: ERASMUS: Per-Patient Incidence of Serious Adverse Events (SAEs) Occurring in ≥ 2%
`of Patients in the SAF .................................................................................................................. 123
`Table 41: ERASMUS: Per-patient Incidence of Serious Adverse Events Occurring in ≥ 2% of
`Patients receiving >800 mCi Lutathera and Occurring More Frequently* than in Patients
`Receiving ≤ 800 mCi by Lutathera Dose Level (SAF) ................................................................... 124
`Table 42: NETTER-1: Per-Patient Incidence of Treatment Emergent Adverse EVENTS Occurring at
`a Higher Incidence in Patients Treated with Lutathera [Between Arm Difference of ≥ 5% (all
`Grades) or ≥ 2% (Grades 3-4)] .................................................................................................... 126
`Table 43: Per-Patient Incidence of Selected Laboratory Abnormalities Occurring in Study 1 at a
`Higher Incidence in Lutathera-Treated Patients [Between Arm Difference of ≥5% (All Grades)1 or
`≥2% (Grades 3-4)]* ..................................................................................................................... 128
`Table 44: NETTER-1: Patients in the SAF Identified to have Hematologic Malignancies/MDS .. 133
`Table 45: NETTER-1: Exploration of MedDRA Primary Terms (MedDRA PT) Potentially related to
`Radiation Effects on the Kidney .................................................................................................. 135
`Table 46: Clinical Trials of Lutathera .......................................................................................... 138
`Table 47: Efficacy Results in ERASMUS by Tumor ...................................................................... 143
`Table 48: Exploratory MedDRA -Based Adverse Event Diagnostic (MAED) Service Analysis of
`Lutathera by MedDRA SOC Classification ................................................................................... 165
`Table 49: Exploratory MedDRA -Based Adverse Event Diagnostic (MAED) Service Analysis of
`Lutathera by MedDRA HLGT Classification ................................................................................. 166
`Table 50: Exploratory MedDRA -Based Adverse Event Diagnostic (MAED) Service Analysis of
`Lutathera by MedDRA HLT Classification ................................................................................... 167
`Table 51: Exploratory MedDRA -Based Adverse Event Diagnostic (MAED) Service Analysis of
`Lutathera by MedDRA PT Classification...................................................................................... 168
`
`
`7
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`
`Table of Figures
`
`
`Figure 1: Radiotherapeutic Effect of a Single Dose Administration of [177Lu]-DOTA-Y3-
`Octreotate to CA20948 Tumor Bearing Lewis Rats (established tumors) .................................... 34
`Figure 2: Effects of Multiple Dose Administration on Tumor Volume ........................................ 35
`Figure 3: Survival of Rats Treated with [177Lu]-DOTA-Y3-Octreotate (3 doses at 30-day interval)
`....................................................................................................................................................... 35
`Figure 4: Anti-Tumor Activity and Renal Injury in CA20948-Implanted Rats .............................. 36
`Figure 5: Fractionation and Amino Acid Effects on Renal Damage ............................................. 37
`Figure 6: Association of 177Lu-DOTA0-Tyr3-Octreotate exposure and baseline creatinine
`clearance ....................................................................................................................................... 49
`Figure 7: Association of 177Lu-DOTA0-Tyr3-Octreotate kidney exposure and renal function using
`Cockcroft-Gault equation ............................................................................................................. 49
`Figure 8: Effect of renal dysfunction on platelet levels per treatment group .............................. 50
`Figure 9: Association of 177Lu-DOTA0-Tyr3-Octreotate exposure and baseline bilirubin .............. 50
`Figure 10: Treatment schema for the LU Treatment Arm ............................................................ 58
`Figure 11: Dose Modifying Schemes for 177Lu-DOTA0-Tyr3-Octreotate Treatment Arm .......... 59
`Figure 12: NETTER-1 Trial: Study Populations .............................................................................. 72
`Figure 13: NETTER-1 Trial: Applicant’s K-M curves for PFS .......................................................... 80
`Figure 14: NETTER-1 Trial: FDA’s K-M curves for PFS ................................................................... 84
`Figure 15: NETTER-1 Trial: K-M Curves for OS -CSR Results ......................................................... 86
`Figure 16: NETTER-1 Trial: K-M Curves for OS Updated Analysis without Imputed Date ............ 87
`Figure 17: ERASMUS: Safety (SAF) and Full Analysis Set (FAS) Data Analysis Sets (A) ............... 100
`Figure 18: ERASMUS: Midgut Progressive Analyses Set (B) ....................................................... 101
`Figure 19: Composition of the Integrated Lutathera Safety Database....................................... 115
`Figure 20: NETTER-1: Patients in Follow-up Over Time .............................................................. 119
`Figure 21: NETTER-1: Time to Platelet Count Nadir by Treatment Group, SAF (N= 123)........... 131
`Figure 22: NETTER-1 Platelet Count Change from Baseline (%) in Patients with
`Thrombocytopenia Following Lutathera Treatment (N=59) ...................................................... 132
`Figure 23: NETTER-1: Change in Creatinine and Creatinine Clearance Over Time by Study Arm,
`SAF............................................................................................................................................... 134
`Figure 24: ERASMUS: Change from baseline in Inhibin B (ng/l) by visit and response. (n=84)
`(Dutch Subset, SAF) ..................................................................................................................... 139
`
`8
`
`
`Version date: February 1, 2016 for initial rollout (NME/original BLA reviews)
`
`Reference ID: 4211167
`
`

`

`NDA/BLA Multidisciplinary Review and Evaluation NDA 207800
`Lutetium Lu 177 Dotatate (Lutathera)
`Reviewers of Multi-Disciplinary Review and Evaluation
`
`
`Regulatory Project Manager
`Nonclinical Reviewer
`Nonclinical Team Leader
`Office of Clinical Pharmacology Reviewer(s)
`Office of Clinical Pharmacology Team Leader(s)
`Clinical Reviewer
`Clinical Team Leader
`Statistical Reviewer
`Cross-Disciplinary Team Leader
`Division Director (DHOT)
`Division Director (OCP)
`Divis