Referral to Amgen Safety Net Foundation Enrollment in .../media/amgen/full/parsabivhcp-com/content/...Amgen Safety Net Foundation may be able to provide Parsabiv™ at no cost to eligible

IndicationParsabiv™ (etelcalcetide) is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.

Limitations of Use:Parsabiv™ has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations.

Important Safety InformationParsabiv™ is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred.

Please see additional Important Safety Information on page 15.

Parsabiv™—the control of calcimimetic delivery you’ve always wanted, the sustained lowering of sHPT lab values your patients deserve1

sHPT = secondary hyperparathyroidism.

Not an actual Parsabiv™ vial. The displayed vial is for illustrative purposes only.

Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 www.amgen.com

©2017 Amgen Inc. All rights reserved. Not for reproduction. USA-416-050663 06-17

References1. Parsabiv™ (etelcalcetide) prescribing information, Amgen.

2. Dataonfile,Amgen;[SummaryofClinicalEfficacy;2015].

3. Dataonfile,Amgen;[CombinedPhase3LabValuesMultipleImputationApproach;2017].

4. BlockGA,BushinskyDA,CunninghamJ,etal.Effectofetelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: two randomized clinical trials. JAMA. 2017;317:146-155.

5. Dataonfile,Amgen;[CombinedPhase3LabValuesOverTime;2016].

6. Dataonfile,Amgen;[IntegratedSummaryofEfficacy;2015].

7. Dataonfile,Amgen;[IntegratedSummaryofSafety;2015].

8. Dataonfile,Amgen;[SummaryofClinicalSafety;2015].

9. Dataonfile,Amgen;[ClinicalStudyReport20120231;2015].

10.CentersforMedicare&MedicaidServices(CMS),HHS.MedicareProgram;End-StageRenalDiseaseProspectivePaymentSystem,andQualityIncentiveProgram. FinalRule.Fed Regist.2015;80(215):68967-69077.

27

Comprehensive coverage and reimbursement support

Medicare reimbursementParsabiv™willbepaidforbyMedicarethroughanadd-onadjustmenttotheESRDPPSbase rate10

*Providedthroughindependentcharitablepatientassistanceprograms;programeligibilityisbasedonthecharity’scriteria.Amgenhasnocontroloverindependent,third-partyprogramsandprovidesreferralsasacourtesy only.

ESRDPPS=end-stagerenaldiseaseprospectivepaymentsystem.

Coverage supportImportant coverage considerations for Parsabiv™

Contact Amgen Assist® at 1-800-272-9376 Monday through Friday, 8:00 am to 8:00 pm ET for coverage and reimbursement support information

Medicare Patients Commercial Insurance Patients

Referral to Independent Co-pay Foundations*

Commercial Insurance Patients

Can reduce Parsabiv™ co-pay to as low as $5 for eligible patients

Enrollment in Parsabiv™ Co-pay Card Program

†

Uninsured/Underinsured Patients

Amgen Safety Net Foundation may be able to provide Parsabiv™ at no cost to eligible patients

Referral to Amgen Safety Net Foundation



Uninsured Patients



2

Getting to know Parsabiv™

Table of Contents

4 What are the fundamentals of Parsabiv™

6 What effect does Parsabiv™ have on parathyroid hormone (PTH) levels

8 How does Parsabiv™ impact PTH level to achieve the study treatment goal

10 What impact does Parsabiv™ have on PTH, phosphate, and corrected calcium levels

12 What adverse reactions were experienced in Parsabiv™ combined phase 3 studies

14 What safety information for Parsabiv™ do I need to know

16 WhatifmypatientsarecurrentlyonSensipar® (cinacalcet) and want to switch to Parsabiv™

Important Safety InformationParsabiv™ lowers serum calcium and can lead to hypocalcemia, sometimes severe.


18 How do I start my patients on Parsabiv™

20 How do I monitor and titrate Parsabiv™

22 How do I manage calcium levels in patients on Parsabiv™

24 How might I expect calcium levels to change in response to Parsabiv™

26 Are there programs available to help my patients

3

4 5

What are the fundamentals of Parsabiv™?

Parsabiv™ gives you control over calcimimetic delivery at the end of hemodialysis1

LOWER 3 key secondary HPT

lab values1*

MAINTAIN lab reductions up to

78weeks1†

CONTROL deliverywithIVadministration1

About Parsabiv™


Important Safety InformationSignificantloweringofserumcalciumcancauseQTintervalprolongationandventriculararrhythmia.PatientswithconditionsthatpredisposetoQTintervalprolongationandventriculararrhythmiamaybeatincreasedriskforQTintervalprolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv™.CloselymonitorcorrectedserumcalciumandQTintervalinpatients at risk on Parsabiv™.


*Resultsarecombinedfromtwo26-week,randomized,double-blind,placebo-controlledstudiescomparingParsabiv™ with placebo in patients with chronic kidney disease (CKD) on hemodialysis.

†Open-labelextension(OLE):datapooledforpatientsreceivingParsabiv™acrosstwoplacebo-controlledparentstudiesandasubsequentOLEstudy,startingfromthebaselineoftheparentstudyuntiltheendortheprespecifiedcutoffdateoftheOLEstudy,whicheverwasearlier.2

P=phosphate;cCa=correctedcalcium;IV=intravenous.

PTHP

cCa

PTHPcCa

PTHP

cCa

PTHPcCa

6 7

What effect does Parsabiv™ have on parathyroid hormone (PTH) levels?

78%ofpatientswhoreceivedParsabiv™ achieved>30%reductioninmeanPTH3

Combined Placebo-Controlled Studies

80

90

100

Parsabiv™ + vitamin D and/or

phosphate binders*(n = 509)

Placebo + vitamin D and/or

phosphate binders*(n = 514)

78.0%

70

60

50

40

30

20

10

0

% o

f pat

ient

s ac

hiev

ing

> 3

0% re

duct

ion

in m

ean

iPTH

from

bas

elin

e

11.1%

P < 0.001

Resultsarecombinedfromtwo26-week,randomized,double-blind,placebo-controlledstudiescomparingParsabiv™ with placebo in patients with chronic kidney disease (CKD) on hemodialysis with intact parathyroid hormone(iPTH)>400pg/mLandcorrectedcalcium≥8.3mg/dL(N=1023).PatientsinbothtreatmentarmscouldbetreatedwithvitaminDsterolsand/orphosphatebinders.MeanbaselineiPTHintheParsabiv™groupandplacebogroupwere847pg/mLand836pg/mL,respectively.Theprimaryendpointofeachstudywastheproportionofpatientswhoachieveda>30%reductionfrombaselineinmeaniPTHduringtheefficacyassessmentperiod(definedasweeks20through27,inclusive).1,2,4

*VitaminDand/orphosphatebinders,ifprescribed.4

Important Safety InformationSignificantreductionsincorrectedserumcalciummaylowerthethresholdforseizures. Patients with a history of seizure disorder may be at increased risk for seizuresiftheydevelophypocalcemiaduetoParsabiv™.Monitorcorrectedserumcalcium in patients with seizure disorders on Parsabiv™.


8 9

How does Parsabiv™ impact PTH level to achieve the study treatment goal?

Initiating Parsabiv™atPTH>400to<600 pg/mLenabled73%ofpatientstoachievethestudy PTH treatment goal3

Patients achieving study iPTH treatment goal by screening iPTH3,4

Parsabiv™ + vitamin D and phosphate binders*

Placebo + vitamin D and phosphate binders*

80

90

100

> 400 to < 600 pg/mL

72.7%

50.7%

10.7%

4.3%

600to≤1000pg/mL

70

60

50

40

30

20

10

0

%ofpatientsachievingiPTH≤300pg/mL

30.4%

1.8%

> 1000 pg/mL

Screening iPTH

(n = 172) (n = 169) (n = 225) (n = 233) (n = 112) (n = 112)

Combined Placebo-Controlled Studies

Resultsarecombinedfromtwo26-week,randomized,double-blind,placebo-controlledstudiescomparingParsabiv™withplaceboinpatientswithCKDonhemodialysiswithiPTH>400pg/mLandcorrectedcalcium≥8.3mg/dL(N=1023).PatientsinbothtreatmentarmscouldbetreatedwithvitaminDsterolsand/orphosphatebinders.MeanbaselineiPTHintheParsabiv™groupandplacebogroupwere847pg/mLand836pg/mL,respectively.Theprimaryendpointofeachstudywastheproportionofpatientswhoachieveda>30%reductionfrombaselineinmeaniPTHduringtheefficacyassessmentperiod(definedasweeks20through 27,inclusive).1,2,4

*VitaminDand/orphosphatebinders,ifprescribed.4

Secondary endpoint: in phase 3 trials, overall, 53.4% of Parsabiv™ patients achieved iPTH ≤ 300 pg/mL vs 5.8% of placebo patients during the efficacy assessment period (P < 0.001)3

•Overall,theaveragedoseofParsabiv™duringtheefficacyassessmentperiodwas7.2mgthreetimesperweek1

• PatientsinitiatedatscreeningiPTH<600pg/mLhadanaveragedoseof5.7mg three times per week1

• PatientsinitiatedatscreeningiPTH600to≤1000pg/mLhadanaveragedoseof7.4mgthreetimesperweek1

• PatientsinitiatedatscreeningiPTH>1000pg/mLhadanaveragedoseof8.7mg three times per week1

Important Safety InformationConcurrent administration of Parsabiv™ with another oral calcimimetic could result in severe,life-threateninghypocalcemia.PatientsswitchingfromcinacalcettoParsabiv™shoulddiscontinuecinacalcetforatleast7dayspriortoinitiatingParsabiv™.Closelymonitor corrected serum calcium in patients receiving Parsabiv™ and concomitant therapies known to lower serum calcium.


10 11

What impact does Parsabiv™ have on PTH, phosphate, and corrected calcium levels?

Combined Placebo-Controlled and Open-Label Extension Studies

Important Safety InformationMeasurecorrectedserumcalciumpriortoinitiationofParsabiv™.Donotinitiateinpatientsifthecorrectedserumcalciumislessthanthelowerlimitofnormal.Monitorcorrectedserumcalciumwithin1weekafterinitiationordoseadjustmentandevery4weeksduringtreatmentwithParsabiv™.MeasurePTH4weeksafterinitiationordoseadjustmentofParsabiv™.Oncethemaintenancedosehasbeenestablished,measure PTH per clinical practice.


Parsabiv™ lowered PTH, phosphate, and corrected calcium3,5

Mean iPTH, phosphate, and corrected calcium over time

-48.5%

Parsabiv™+16.9%

Placebo

n=509

-8.0%

Parsabiv™-1.9%

Placebo

-7.0%

Parsabiv™+0.1%

Placebo

Placebo-controlledtreatmentperiod:resultsarecombinedfromtwo26-week,randomized,double-blind,placebo-controlledstudiescomparingParsabiv™ with placebo in patients with CKD on hemodialysis with iPTH>400pg/mLandcorrectedcalcium≥8.3mg/dL(N=1023).PatientsinbothtreatmentarmscouldbetreatedwithvitaminDsterolsand/orphosphatebinders.MeanbaselineiPTHintheParsabiv™ group and placebo groupwere847pg/mLand836pg/mL,respectively.Theprimaryendpointofeachstudywastheproportionofpatientswhoachieveda>30%reductionfrombaselineinmeaniPTHduringtheefficacyassessmentperiod(definedasweeks20through27,inclusive).1,2,4

Pleaseseepage25forstudydesignofopen-labelextension.

*ValuesrepresentmeaniPTH,P,cCaduringefficacyassessmentperiod,definedasweeks20through27,inclusive.3

†VitaminDand/orphosphatebinders,ifprescribed.4

vs

vs

vs

iPTH

P

cCa

Reductions in PTH, phosphate, and corrected calcium levels were maintained for up to 78 weeks1

Mean % change from baselineP<0.001vsplacebo

Parsabiv™ + vitamin D and phosphate binders†

Placebo + vitamin D and phosphate binders†

n=514

n=509 n=514

n=509 n=514

Starting at week 27, no study drug was administered as part of a 30-day follow-up while patients transitioned studies


n = 514 n = 414Placebo


Placebo n = 514 n = 411


Reductions in phosphate levels were maintained for up to 78 weeks

Reductions in iPTH levels were maintainedfor up to 78 weeks

Reductions in corrected calcium levels were maintainedfor up to 78 weeks

Open-label extension study period

30-day washout phase



200

Baseline

n = 509 n = 431

n = 501 n = 437

n = 509 n = 436

Mea

n iP

TH (p

g/m

L)

Study week4 8 12 16 20 24

400

600

800

1000

0

Parsabiv™

Parsabiv™

Mea

n ph

osph

ate

(mg/

dL)

4.5

5.0

5.5

6.0

8.5

Mea

n co

rrec

ted

calc

ium

(mg/

dL)

9.0

9.5

10.0

10.5

8.0

Parsabiv™

936* 836

5.6*

5.8

9.7*9.7

5.3*

5.9

9.0*

9.6

421*

847

Open-label extension study periodBaseline

Study week4 8 12 16 20 24


Study week4 8 12 16 20 24

345‡

5.0‡

8.9‡

n = 364 n = 147

n = 380 n = 144

n = 381 n = 146

27 31 35 39 47 55 63 71 78

27 31 35 39 47 55 63 71 78

27 31 35 39 47 55 63 71 78





Placebo n = 514 n = 411









200

Baseline

n = 509 n = 431

n = 501 n = 437

n = 509 n = 436

Mea

n iP

TH (p

g/m

L)

Study week4 8 12 16 20 24

400

600

800

1000

0

Parsabiv™

Parsabiv™

Mea

n ph

osph

ate

(mg/

dL)

4.5

5.0

5.5

6.0

8.5

Mea

n co

rrec

ted

calc

ium

(mg/

dL)

9.0

9.5

10.0

10.5

8.0

Parsabiv™

936* 836

5.6*

5.8

9.7*9.7

5.3*

5.9

9.0*

9.6

421*

847


Study week4 8 12 16 20 24


Study week4 8 12 16 20 24

345‡

5.0‡

8.9‡

n = 364 n = 147

n = 380 n = 144

n = 381 n = 146

27 31 35 39 47 55 63 71 78

27 31 35 39 47 55 63 71 78

27 31 35 39 47 55 63 71 78





Placebo n = 514 n = 411









200

Baseline

n = 509 n = 431

n = 501 n = 437

n = 509 n = 436

Mea

n iP

TH (p

g/m

L)

Study week4 8 12 16 20 24

400

600

800

1000

0

Parsabiv™

Parsabiv™

Mea

n ph

osph

ate

(mg/

dL)

4.5

5.0

5.5

6.0

8.5

Mea

n co

rrec

ted

calc

ium

(mg/

dL)

9.0

9.5

10.0

10.5

8.0

Parsabiv™

936* 836

5.6*

5.8

9.7*9.7

5.3*

5.9

9.0*

9.6

421*

847


Study week4 8 12 16 20 24


Study week4 8 12 16 20 24

345‡

5.0‡

8.9‡

n = 364 n = 147

n = 380 n = 144

n = 381 n = 146

27 31 35 39 47 55 63 71 78

27 31 35 39 47 55 63 71 78

27 31 35 39 47 55 63 71 78

12 13

What adverse reactions were experienced in Parsabiv™ combined phase 3 studies?

Adversereactionsreportedin≥5%of Parsabiv™-treatedpatients1

*Includedadversereactionsreportedwithatleast1%greaterincidenceintheParsabiv™groupcomparedtotheplacebo group.

†Asymptomaticreductionsincorrectedserumcalciumbetween8.3mg/dLand>7.5mg/dL(clinicallysignificantreductionsthatrequiredmedicalmanagement)orreductionsincalciumbelow7.5mg/dL.

‡Symptomaticreductionsincorrectedserumcalcium<8.3mg/dL.

§ Paresthesia includes preferred terms of paresthesia and hypoesthesia.

Discontinuations•Overall,inplacebo-controlledstudies,1.8%ofpatientsintheParsabiv™group and2.5%ofpatientsintheplacebogroupdiscontinuedtreatmentduetoan adverse event7

Low serum calcium•Mosteventsofbloodcalciumdecreaseorhypocalcemiaweremildormoderatein

severity in both the placebo and Parsabiv™ groups7,8

• Incombinedplacebo-controlledstudies,1%ofpatientswhoreceivedParsabiv™discontinuedtreatmentduetolowcorrectedserumcalciumvs0%withplacebo1

Adverse Reactions

Combined placebo-controlled studies

Diarrhea

Nausea

Vomiting

Adverse Reaction*

Blood calcium decreased†

Muscle spasms

Diarrhea

Nausea

Vomiting

Headache

Hypocalcemia‡

Paresthesia§

Placebo(N = 513)

%

10

7

9

6

5

6

0.2

1

64

12

11

11

9

8

7

6

%

Parsabiv™(N = 503)

Please see Important Safety Information on page 15.

14 15

Important Safety Information

What safety information for Parsabiv™ do I need to know?

Contraindication: Parsabiv™ is contraindicated in patients with known hypersensitivity to etelcalcetide or any of its excipients. Hypersensitivity reactions, including pruritic rash, urticaria, and face edema, have occurred.

Hypocalcemia: Parsabiv™ lowers serum calcium and can lead to hypocalcemia, sometimessevere.SignificantloweringofserumcalciumcancauseQTintervalprolongationandventriculararrhythmia.PatientswithconditionsthatpredisposetoQTintervalprolongationandventriculararrhythmiamaybeatincreasedriskforQTinterval prolongation and ventricular arrhythmias if they develop hypocalcemia due to Parsabiv™.CloselymonitorcorrectedserumcalciumandQTintervalinpatientsatriskon Parsabiv™.

Significantreductionsincorrectedserumcalciummaylowerthethresholdforseizures.Patients with a history of seizure disorder may be at increased risk for seizures if they develophypocalcemiaduetoParsabiv™.Monitorcorrectedserumcalciuminpatientswith seizure disorders on Parsabiv™.

Concurrent administration of Parsabiv™ with another oral calcimimetic could result in severe,life-threateninghypocalcemia.PatientsswitchingfromcinacalcettoParsabiv™shoulddiscontinuecinacalcetforatleast7dayspriortoinitiatingParsabiv™.Closelymonitor corrected serum calcium in patients receiving Parsabiv™ and concomitant therapies known to lower serum calcium.

MeasurecorrectedserumcalciumpriortoinitiationofParsabiv™.Donotinitiateinpatientsifthecorrectedserumcalciumislessthanthelowerlimitofnormal.Monitorcorrectedserumcalciumwithin1weekafterinitiationordoseadjustmentandevery4weeksduringtreatmentwithParsabiv™.MeasurePTH4weeksafterinitiationordoseadjustmentofParsabiv™.Oncethemaintenancedosehasbeenestablished,measurePTH per clinical practice.

Worsening Heart Failure: In Parsabiv™ clinical studies, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. Closely monitor patients treated with Parsabiv™ for worsening signs and symptoms of heart failure.

Upper Gastrointestinal Bleeding: In clinical studies, 2 patients treated with Parsabiv™ in1253patientyearsofexposurehaduppergastrointestinal(GI)bleedingatthetimeof death. The exact cause of GI bleeding in these patients is unknown and there were too few cases to determine whether these cases were related to Parsabiv™.

Patients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may be at increased risk for GI bleeding with Parsabiv™. MonitorpatientsforworseningofcommonParsabiv™GIadversereactionsandforsigns and symptoms of GI bleeding and ulcerations during Parsabiv™ therapy.

Adynamic Bone: Adynamic bone may develop if PTH levels are chronically suppressed.

Adverse Reactions: In clinical trials of patients with secondary HPT comparing Parsabiv™ to placebo, the most common adverse reactions were blood calcium decreased(64%vs.10%),musclespasms(12%vs.7%),diarrhea(11%vs.9%), nausea(11%vs.6%),vomiting(9%vs.5%),headache(8%vs.6%),hypocalcemia (7%vs.0.2%),andparesthesia(6%vs.1%).

Please see accompanying Parsabiv™ full Prescribing Information.

ImportantSafetyInformation

16 17

What if my patients are currently on Sensipar® (cinacalcet) and want to switch to Parsabiv™?

PatientsmustdiscontinueSensipar® (cinacalcet) foratleast7daysbeforestartingParsabiv™

How to Switch to Parsabiv™

How to switch from Sensipar® to Parsabiv™EnsureyourpatientdiscontinuesuseofSensipar®tabletsforatleast7dayspriorto starting Parsabiv™.1

after day 7, if correctedserum calcium is at or above lower limit of normal*

7-day discontinuation of Sensipar®

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

Initiate Parsabiv™

Pills are not actual size

*Lowerlimitofreferencerangeinphase3trialswas8.3mg/dL.1,4

Important Safety InformationIn Parsabiv™ clinical studies, cases of hypotension, congestive heart failure, and decreased myocardial performance have been reported. Closely monitor patients treated with Parsabiv™ for worsening signs and symptoms of heart failure.


18 19

How do I start my patients on Parsabiv™?

• EnsurecorrectedserumcalciumisatorabovethelowerlimitofnormalpriortoParsabiv™ initiation, a dose increase, or reinitiation after dosing interruption1

• InitiateParsabiv™at5mg,3timesperweek1

•AdministerParsabiv™byintravenousbolusinjectionintothevenouslineofthe dialysiscircuitattheendofthehemodialysistreatmentduringrinsebackorIV after rinse back1

• Do not administer Parsabiv™ more frequently than 3 times per week1

Initiating patients on Parsabiv™

Initiating Parsabiv™

Important Safety InformationInclinicalstudies,2patientstreatedwithParsabiv™in1253patientyearsofexposurehad upper gastrointestinal (GI) bleeding at the time of death. The exact cause of GI bleeding in these patients is unknown and there were too few cases to determine whether these cases were related to Parsabiv™.


• If a regularly scheduled hemodialysis treatment is missed, DONOT administer anymisseddoses.ResumeParsabiv™ at the end of the next hemodialysis treatment at the prescribed dose1

• If doses of Parsabiv™ are missed for more than 2 weeks, reinitiate Parsabiv™ at the recommended starting dose of5mg(or2.5mgifthat was the patient’s last dose)1

5 mg 3xa weekstarting dose

Duringrinse back

orIV after

rinse back2.5mg/

0.5mL

10mg/

2mL1mL

5mg/

Parsabiv™ is available in 3 different, single-use, single-dose vials

Vials shown are actual size

2.5mg/ 0.5mL

5mg/ 1mL

10mg/ 2mL

20 21

How do I monitor and titrate Parsabiv™?

Lab monitoring during Parsabiv™ treatment

Titrating up:

• IncreasethedoseofParsabiv™in2.5mgor5mgincrementsuntilPTHiswithinrecommended target range and corrected serum calcium is within normal range

• Increase no more frequently than every 4weeksuptoamaximumdoseof15mgthree times per week

Titrating down:

• Decrease or temporarily discontinue Parsabiv™ when PTH is below target range

• Consider decreasing or temporarily discontinuing Parsabiv™, or use concomitant therapies,* when corrected serum calcium is below lower limit of normal†but≥7.5mg/dLwithout symptoms of hypocalcemia

Reinitiating Parsabiv™:

• If dose is stopped, reinitiate Parsabiv™ at a lower dose when PTH is within target range and hypocalcemia has been corrected

*Concomitanttherapiesincludecalcium,calcium-containingphosphatebinders,and/or vitamin D sterols or increases in dialysate calcium concentration.†Lowerlimitofreferencerangeinphase3trialswas8.3mg/dL.1,4

Flexible dosing that you control with IVadministration1

Titrate up or down as needed based on PTH and corrected serum calcium

Lab Monitoring and Titration

Important Safety InformationPatients with risk factors for upper GI bleeding, such as known gastritis, esophagitis, ulcers or severe vomiting, may be at increased risk for GI bleeding with Parsabiv™. MonitorpatientsforworseningofcommonParsabiv™GIadversereactionsandforsigns and symptoms of GI bleeding and ulcerations during Parsabiv™ therapy.


PTH Corrected Serum Calcium

Lab measurements afterinitiation or dose adjustment

Lab measurements once maintenance dose is established

after 4 weeks at 1 week

per clinical practice every 4 weeks

MAXIMUM DOSE15 mg

12.5 mg

7.5 mg

5 mg

2.5 mg

10 mg

STARTING DOSE

Titrateup or down

MAXIMUM DOSE15 mg

12.5 mg

7.5 mg

2.5 mg

10 mgTitrateup or down

5 mg STARTING DOSE

22 23

How do I manage calcium levels in patients on Parsabiv™?

ManagingcalciuminpatientstakingParsabiv™1

Managing Calcium

Important Safety InformationAdynamic bone may develop if PTH levels are chronically suppressed.


• Consider decreasing or temporarily discontinuing Parsabiv™ or use concomitant therapies to increase corrected serum calcium (including calcium,calcium-containingphosphatebinders,and/orvitaminDsterolsor increases in dialysate calcium concentration)

Adjust Treatment as Needed

• Stop Parsabiv™ and treat hypocalcemia

• Start or increase calcium supplementation (including calcium, calcium-containingphosphatebinders,and/or vitamin D sterols or increases in dialysate calcium concentration)

Withhold Parsabiv™

and Monitor

Initiate Parsabiv™

• Do not initiate Parsabiv™ if corrected serum calcium is less than the lower limit of normal*

• Monitor corrected serum calcium within 1 week after initiation or dose adjustment and every 4 weeks during treatment with Parsabiv™.Educatepatients on the symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur

• Throughout the studies, dialysate calcium concentration could be adjusted but had to remain ≥ 2.25 mEq/L1

• Significant lowering of serum calcium can cause paresthesias, myalgias, muscle spasms, seizures, QT interval prolongation, and ventricular arrhythmias1

*Lowerlimitofreferencerangeinphase3trialswas8.3mg/dL.1,4

≥ 8.3 mg/dL*

< 8.3 mg/dL to

≥ 7.5 mg/dL*without symptoms of hypocalcemia

< 7.5 mg/dLor with symptoms of hypocalcemia

When cCa returns ≥ 8.3 mg/dL* —

Reinitiate Parsabiv™

• When corrected serum calcium levels are within normal limits, symptoms of hypocalcemia have resolved, and predisposing factors for hypocalcemia have been addressed, reinitiate Parsabiv™ at a dose 5mglowerthanthelastadministereddose.Ifpatient’s last administered dose of Parsabiv™ was 2.5mgor5mg,reinitiateatadoseof2.5mg

24 25

How might I expect calcium levels to change in response to Parsabiv™?

Calcium reductions were most prominent early in treatment5

•RefertorecommendationsonmonitoringandmanagingcalciuminpatientstakingParsabiv™ on page 23

Placebo-controlledtreatmentperiod:resultsarecombinedfromtwo26-week,randomized,double-blind,placebo-controlledstudiescomparingParsabiv™withplaceboinpatientswithCKDonhemodialysiswithiPTH >400pg/mLandcorrectedcalcium≥8.3mg/dL(N=1023).PatientsinbothtreatmentarmscouldbetreatedwithvitaminDsterolsand/orphosphatebinders.MeanbaselineiPTHintheParsabiv™groupandplacebogroupwere847pg/mLand836pg/mL,respectively.Theprimaryendpointofeachstudywastheproportionofpatientswhoachieveda>30%reductionfrombaselineinmeaniPTHduringtheefficacyassessmentperiod(definedasweeks20through27,inclusive).1,2,4

Open-labelextension:datapooledforpatientsreceivingParsabiv™acrosstwoplacebo-controlledparentstudiesandasubsequentopen-labelextension(OLE)study,startingfromthebaselineoftheparentstudyuntiltheendortheprespecifiedcutoffdateoftheOLEstudy,whicheverwasearlier.Weeks27to31werethe30-daydrug-freeperiod(the30-dayfollow-upperiodofthephase3studybeforeentryintotheextensionstudy).2DuringtheOLE,thestartingdoseofParsabiv™forallsubjectswas5mg.TheParsabiv™dosecouldbeincreasedatOLEweeks5,9,17,25,33,41,and49toamaximumdoseof15mgtoachievepredialysisserumiPTH≤300pg/mLwhilemaintainingappropriateserumcCaconcentrations.InvestigatorswereblindedtoiPTHresultsduringthefirst10weeksoftreatment.Subsequentdoseadjustmentwasdeterminedbytheinvestigatorperprotocolguidelines.9

*Startingatweek27,nostudydrugwasadministeredaspartofa30-dayfollow-upwhilepatients transitioned studies.2

†ValuerepresentscCameasuredatthefirsthemodialysissessioninweek79.5

Managing Calcium

Mean corrected calcium was maintained above the lower limit of normal for up to 78 weeks5

Important Safety InformationIn clinical trials of patients with secondary HPT comparing Parsabiv™ to placebo, themostcommonadversereactionswerebloodcalciumdecreased(64%vs.10%),musclespasms(12%vs.7%),diarrhea(11%vs.9%),nausea(11%vs.6%),vomiting(9%vs.5%),headache(8%vs.6%),hypocalcemia(7%vs.0.2%),andparesthesia(6%vs.1%).


Return to baseline after 4-week discontinuation2,5*

Study week

Placebo-controlled parent study period


30-daywashoutphase

12 20 31 780

8.5

9.0

9.5

10.0

10.5

8.0

Mea

n co

rrec

ted

calc

ium

(mg/

dL)

9.6

8.9†9.0

9.6

4 8 16 24 27 35 39 47 55 63 71

n = 509 n = 436Parsabiv™ n = 381 n = 146

26

Are there programs available to help my patients?

Coverage

Please see Important Safety Information on page 15.




















27












†






Uninsured Patients






















27












†






Uninsured Patients



Documents

Referral to Amgen Safety Net Foundation Enrollment in .../media/amgen/full/parsabivhcp-com/content/...Amgen Safety Net Foundation may be able to provide Parsabiv™ at no cost to eligible