This information is for Healthoe re
`
`Go to Patients 5:.
`
`Caregivers site
`
`TDMOOO211740
`
`HI
`
`1 Professionals
`g.) Kadcyla
`sfln-tastuaurtsn erntarsins
`
`Safetv first! Read bElCrW to see the
`
`imports nt Safetv lnformat ion
`
`Important Safety Information
`
`Boxed WARNINGS:
`
`HEPATOTOXICITV, CARDIAC
`
`TIIIIII'ICIwGIT‘I'flr EMBRYD-FETAL
`
`TICIIIKIwIIIT‘IIr
`
`Iona-l .rlJlrilII-n 'I-rn-I'Irrlnn'l- Infill-I. "PEN-VI. A
`
`* Do Not Substitute ILADC‘I'LA for or With
`
`Trastuzu mah
`
`* Hepatotoxicitv: Serious hepatotonficitvllr has
`
`been reported, including liver failure and
`
`death in patients treated with KADIIVLA.
`Monitor serum transaminases and hiliruhin
`
`prior to initiation of ICADC‘I'LA treatment and
`
`prior to each KADCYLA dose. Fleduce dose
`
`or discontinue ILADC‘I'LA as appropriate in
`cases of increased serum transaminases or
`
`total hiliruhin
`
`* lIllardiac Toxicitv: ICADC‘I'LA administration
`
`mavllr lead to reductions in left ventricular
`
`ejection fraction [LVEFL Evaluate left
`
`ventricular function in all patients prior to
`
`IMMUNOGEN 2226. pg. 1
`Phigenix v. Immunogen
`|PR2014-00676
`
`1
`
`IMMUNOGEN 2226, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthee re
`
`Professionals
`
`@Kadcgla”
`
`allU-lT-E‘ElUEUlTfifl Bmlfll'filllfi
`I
`ll-'
`'.I
`
`Caregivers site
`
`Go to Patients 5:.
`
`
`
`
`Safetv first! Read below to see the
`
`lm ports nt Safetv lnformat ion
`
`ventricular function in all patients prior to
`
`and during treatment with KADEVLA.
`
`With hold treatment for clinicallvllr significant
`decrease in left ventricular function
`
`' Emhrvo-Fetal Toxicitv: Exposure to
`
`KADC‘I'LA can result in emhrvo-fetal death
`
`or birth defects. Advise patients of these
`rislts and the need for effective
`
`contraception
`
`Pregnancv Hegistrv
`
`Additional Important Safety
`
`Information
`
`Left Ventricular Dvsfunction ILVDI
`
`' Patients treated with KADCYLA are at
`
`increased risk of developing L‘UD. In EMILIA,
`
`L‘U'D occurred in 1.8% of patients in the
`
`KADCYLA—treated group and in 3.3% of
`
`patients in the comparator group.
`
`Permanentlyr discontinue KADCYLA if L‘v'EF
`
`has not improved or has declined further
`
`IMMUNOGEN 2226. pg. 2
`Phigenix v. Immunogen
`|PR2014-00676
`
`2
`
`IMMUNOGEN 2226, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Heslthoa re
`
`Professionals
`
`@Kadcgla”
`
`allU-lT-E‘ElUEUlTfifl Bmlfll'filllfi
`I
`ll-'
`'.I
`
`Caregivers site
`
`Go to Patients .'-
`
`
`
`
`Safety first! Read below to see the
`
`lmportant Safety information
`
`' Advise patients to contact their healthcare
`
`proyider immediately if they suspect they
`
`may be pregnant. Encourage women who
`
`may be exposed to KADCTLA during
`
`pregnancy to enroll in the MotHEH
`
`Pregnancy Registry by contacting
`
`1 [sum fififl-Eiflll}
`
`Pulmonary Toxicity
`
`permanentlyr discontinued due to infusion-
`
`' Cases of interstitial lung disease [ILDL
`
`including pneumonitis, some leading to
`
`acute respiratory distress syndrome or fatal
`
`outcome have been reported in clinical trials
`
`with KADCYLA. ln EMILIA, the overall
`
`frequency of pneumonitis was 1.2%
`
`* Treatment with KADCYLA should be
`
`permanently discontinued in patients
`
`diagnosed with IL[11I or pneumonitis
`
`Infusion—Related Reactions, Hypersensitivity Reactions
`
`' Treatment with KADCYLA has not been
`
`studied in patients who had trastuzumah
`
`IMMUNOGEN 2226. pg. 3
`Phigenix v. Immunogen
`|PR2014-00676
`
`3
`
`IMMUNOGEN 2226, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthee re
`
`Professionals
`
`@Kadcgla”
`
`allU-lT-E‘ElUEUlTfifl Bmlfll'filllfi
`I
`ll-'
`'.I
`
`Go to Patients .'-
`
`Caregivers site
`
`
`Safety first! Read lJElCrW to see the
`
`Important Safety information
`
`studied in patients who had trastuzumah
`
`permanently discontinued due to infusion-
`
`related reactions [lftft]: anda'or
`
`hypersensitivity reactions; treatment with
`KADCYLA is not recommended for these
`
`patients. In EMILIA, the overall frequency of
`
`IFtFts in patients treated with KADC‘I’LA was
`1.4%
`
`KADCYLA treatment should be interrupted
`
`in patients with severe lftft and permanently
`discontinued in the event of a life-
`
`threatening lFtFt. Patients should be closely
`
`monitored for lFtFt reactions, especially
`
`during the first infusion
`
`Thronimcytopenia
`
`lnE‘I'ii-u‘l'n .r'lnlen mnflifirnfinn: 5|: nnnrnnrin‘l'n
`
`' In EMILIA, the incidence of 3: Grade 3
`
`thromhocytopenia was ‘M.5% in the
`
`KADCYLA—treated group and {1.4% in the
`
`comparator group [overall incidence 31.2%
`
`and 3.3%, respectively}
`
`' Monitor platelet counts prior to initiation of
`
`KADCYLA and prior to each KADCYLA dose.
`
`IMMUNOGEN 2226. pg. 4
`Phigenix v. Immunogen
`|PR2014-00676
`
`4
`
`IMMUNOGEN 2226, pg. 4
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Heelthee re
`
`Professionals
`
`@Kadcgla”
`
`allU-lT-E‘ElUEUlTfifl Bmlfll'filllfi
`I
`ll-'
`'.I
`
`G o to Patients .'-
`
`Caregivers site
`
`
`Safety first! Read lJElCrW to see the
`
`Important Safety information
`
`Institute dose modifications as appropriate
`
`Neurotoxis'rty
`
`' In EMILIA, the incidence of 3: Grade 3
`
`peripheral neuropathy was 2.2% in the
`
`KADCYLA—treated group and {1.2% in the
`
`comparator group [overall incidence 21.2%
`
`and 13.5%, respectiyely}
`
`' Monitor for signs or symptoms of
`
`neurotoxicity. KADCTLA should be
`
`temporarily discontinued in patients
`
`experiencing Grade 3 or 4 peripheral
`
`neuropathy until resolution to 1: Grade 2
`
`I_ unnmn .l. _I:_:__I _J..__I:__ ____l.:___
`
`HERE Testing
`
`' Detection of HERE protein overexpression or
`
`gene amplification is necessary for selection
`
`of patients appropriate for KADCYLA.
`
`Perform using FDA approved tests by
`
`laboratories with demonstrated proficiency
`
`Extrayns-ation
`
`-
`
`IMMUNOGEN 2226. pg. 5
`Phigenix v. Immunogen
`|PR2014-00676
`
`5
`
`IMMUNOGEN 2226, pg. 5
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Heelthce re
`
`Professionals
`
`@Kadcgla”
`
`afln-h’aatuzun‘afl emtamins
`|
`iI-- '.I
`
`Go to Patients 5:.
`
`Caregivers site
`
`
`Safety first! Read below to see the
`
`Important Safety information
`
`'I In KADCYLA clinical studies, reactions
`
`secondary to extrayasation have been
`
`observed and were generally mild. The
`
`infusion site should be closely monitored
`
`for possible subcutaneous infiltration
`
`during drug administration. Specific
`treatment for KADCYLA extrayasation is
`
`unknown
`
`Nursing Mothers
`
`thrombocytooenia. increased
`
`' Discontinue nursing or discontinue
`
`KADCYLA taking into consideration the
`
`importance of the drug to the mother
`
`Adverse Reactions
`
`' The most common ADFts seen with
`
`KADCYLA in EMILIA [frequency 3:- 25%} we re
`
`nausea, fatigue, musculoslteletal pain,
`
`thrombocytopenia, increased
`
`transaminases, headache, and constipation.
`
`The most common NCI-CTCAE [version 3]: 3:
`
`Grade 3 ADHs [frequency es 2%} were
`
`IMMUNOGEN 2226. pg. 6
`Phigenix v. Immunogen
`|PR2014-00676
`
`6
`
`IMMUNOGEN 2226, pg. 6
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthoa re
`
`Professionals
`
`@Kadcgla”
`
`allU-lT-E‘ElUEUWfifl Bmlfli'fililfi
`I
`ll-'
`'.I
`
`Go to Patients .'-
`
`Caregivers site
`
`
`Safetjr first! Read lJElCrW to see the
`
`Important Safety lnformation
`ll-f'II—f'I-l'lI—I'I mun-u llll-‘I-f uu-uu-uu-u...u-- I-ll'I-f
`
`importance of the drug to the mother
`
`Adverse Reactions
`
`Boxed WAHMMGS.
`
`' The most common ADFts seen with
`
`KADCYLA in EMILIA [frequencyr :- 25%} we re
`
`nausea, fatigue, musculoslteletal pain,
`
`thromhocy'topenia, increased
`
`transaminases, headache, and constipation.
`
`The most common NCI-CTCAE [version 3]: 3:
`
`Grade 3 ADHs [freq uencyr es 2%} were
`
`thromhocy'topenia, increased
`
`transaminases, anemia, hypokalemia,
`
`peripheral neuronathyir and fatigue
`
`You are encouraged to re port side effects to Genentech and
`
`the FDA- 1|I"'ou n'1ia1,.lr contact Genentech by calling
`
`'I [333] 335-2555. 1||"'ou mam:r contact the FDA l:'_I1,.Ir 1.irisitin-g
`
`1I.tv.i'iilii'iilii'.fda.gomIrmedwatch or calling
`
`1 [301}! FDA-103:3.
`
`Please see swamps nving full Prescribing Info rmation
`
`for additional inmorta nt safety information, including
`
`IMMUNOGEN 2226. pg. 7
`Phigenix v. Immunogen
`|PR2014-00676
`
`7
`
`IMMUNOGEN 2226, pg. 7
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthca re
`
`IBrofessionals
`
`:QKadcgla"
`
`.n.
`.-.--\.r - ma.- afi- -\..--\.'
`.-.-.-
`..
`.t_. H s
`..
`.
`.t
`'JJ-l '* Llfl
`1| -=
`all“-
`
`Caregivers site
`
`=-=-
`
`'3 o to Patients Ell.
`
`
`
`
`Safety first! Press here to read the Important
`
`Safety Information
`
`The First antibcdg-drug conjugate For the treatment of
`
`HERE-positive [HEH2+] metastatic breast cancer
`
`[MEIE]
`
`View Prc posed Hec ha nisrn of Action
`
`l[Jontact a Representative
`
`Learn more about KADCYLA. Press below for an appointment
`
`with a clinical oncologist specialist.
`
`a l[iontactluns
`
`a Learn more
`
`Tools Sr Resources
`
`{/—
`
`1c Dosing and Administration saw TDM°°°1360901
`
`1c Dose Modification Worksheet
`
`TDM0001545301
`
`1c Mediation Distinction Poster9 TDM0001447200
`
`1: Nurse—tc-Patient Tear Sheet
`
`TDM0001361301
`
`ll'Jlinical Data Available
`
`Review significant su rvival results and the adverse reaction
`
`profile demonstrated in the Phase III EIu'lILIA trial-
`
`Indication
`
`IlliADIIZYLA= "l [ado—trastuzumab emtansine}, as a single
`agent, is indicated for the treatment of patients with HER2—
`
`positive [HER2+}, metastatic breast cancer [MBE} who
`
`previously received trastuzumab and a taxane, separately or
`
`in combination. Patients should have either:
`
`* Received prior therapy for metastatic disease, or
`
`* Developed disease recurrence during or within six
`
`months of completing adjuvant therapy
`
`Important Safety Information
`
`Boxed WARNINGS: HEPATICIIITICIIGl'lIIlIIIT"I"'.r
`
`lSARDIAlII Tliillll'lllllllT"|“'.r ENIRRYD-FEI'AL
`
`TDXIGITY
`
`* Do Not Substitute HEADCYLA for or with Trastuzumab
`
`* Hepatotoxicity: Serious hepatotoxicity has been
`
`reported, including liver failure and death in patients
`
`treated with KADCYLA. N'Ionitor serum transaminases
`
`and bilirubin prior to initiation of IEADflYLA treatment
`
`and prior to each IEADflYLA dose. Reduce dose or
`
`discontinue IEADtlYLA as appropriate in cases of
`
`increased serum transaminases or total bilirubin
`
`* l[lardiac Toxicity: IEADCYLA administration may lead
`
`to reductions in left ventricular ejection fraction
`
`[LVEFL Evaluate left ventricular function in all
`
`patients prior to and during treatment with IEADIIYLA.
`
`With hold treatment for clinically significant decrease
`
`in left ventricular function
`
`* Embryo-Fetal Toxicity: Exposure to IEAD'IIYLA can
`
`result in embryo-fetal death or birth defects. Advise
`
`patients of these risks and the need for effective
`
`contraception
`
`Additional Important Safety Information:
`
`Left Ventricular Dysfunction lLifDl
`
`* Patients treated with ICADCYLA are at increased risk of
`
`developing LYD. In EMILIA, LYD occurred in 1.3% of
`
`patients in the ICADCYLA—treated group and in 3.3% in
`
`the comparator group. Permanently discontinue
`
`KADCYLA if LYEF has not improved or has declined
`
`further
`
`Pregnancy Registry
`
`* Advise patients to contact their healthcare provider
`
`immediately if they suspect they may be pregnant.
`
`Encourage women who may be exposed to ICADEYLA
`
`during pregnancy to enroll in the MotHER Pregnancy
`
`Registry by contactng 1 {sec} Still-6220
`
`Pulmonary Toxicity
`
`* Cases of interstitial lung disease [|LD}, including
`
`pneumonitis, some leading to acute respiratory
`
`distress syndrome or fatal outcome have been
`
`reported in clinical trials with KADCYLA. In EMILIA,
`
`the overall frequency of pneumonitis was ‘1 .2%
`
`* Treatment with ICADEYLA should be permanently
`
`discontinued in patients diagnosed with ILD or
`
`pneumonitis
`
`Infusion-Related Reactions, Hypersensitivity Reactions
`
`* Treatment with ICADEYLA has not been studied in
`
`patients who had trastuzumab permanently
`
`discontinued due to infusion—related reactions [IRR}
`
`andlor hypersensitivity reactions; treatment with
`
`KADCYLA is not recommended for these patients. In
`
`EMILIA, the overall frequency of IRRs in patients
`
`treated with ICADCYLA was 1.4%
`
`* ICADEYLA treatment should be interrupted in patients
`
`with severe IRR and permanently discontinued in the
`
`event of a life-threatening IRR. Patients should be
`
`closely monitored for IRR re actions, especially during
`
`the first infusion
`
`Throniaocytopenia
`
`* In EMILIA, the incidence of 2 Grade 3
`
`thrombocytopenia was 111.5% in the ICADCYLA—treated
`
`group and {131% in the comparator group [overall
`
`incidence 31.2% and 3.3%, respectively}
`
`1* Monitor platelet counts prior to initiation of KADCYLA
`
`and prior to each ICADCYLA dose. Institute dose
`
`modifications as appropriate
`
`Neurotoxicity
`
`1* In EMILIA, the incidence of 2 Grade 3 peripheral
`
`neuropathy was 2.2% in the KADEYLA—treated group
`
`and l[1.2% in the comparator group [overall incidence
`
`21.2% and 13.5%, respectively}
`
`* Monitor for signs or symptoms of neurotoxicity.
`
`KADCYLA should be temporarily discontinued in
`
`patients experiencing Grade 3 or 4 peripheral
`
`neuropathy until resolution to 5 Grade 2
`
`HERI2 Testing
`
`* Detection of HER2 protein overexpression or gene
`
`amplification is necessary for selection of patients
`
`appropriate for KADCYLA. Perform using FDA
`
`approved tests by laboratories with demonstrated
`
`proficiency
`
`Extravasaticn
`
`* In KADEYLA clinical studies, re actions secondary to
`
`extravasation have been observed and were
`
`generally mild. The infusion site should be closely
`
`monitored for possible subcutaneous infiltration
`
`during drug administration. Specific treatment for
`
`ICADCYLA extravasation is unknown
`
`Nursing Mothers
`
`* Discontinue nursing or discontinue KADCYLA taking
`
`into consideration the importance of the drug to the
`
`mother
`
`Adverse Reactions
`
`* The most common ADRs seen with HADEYLA in
`
`EMILIA [frequency 1:- 25%} were nausea, fatigue,
`
`musculoskeletal pain, thrombocytopenia, increased
`
`transaminases, headache, and constipation. The
`
`most common NCl—CTCAE [version 3} 3: Grade 3 ADRs
`
`[frequency 3:- 2%} were th rombocytopenia, increased
`
`transaminases, anemia, hypokalemia, peripheral
`
`neuropathy and fatigue
`
`You are encouraged to report side effects to Genentech and
`
`the FDA. You may contact Genentech by calling
`
`1 {SEE} 335-2555. You may contact the FDA by visiting
`
`www.fda.govfmedwatch or calling 1 [8111]} FDA-103:3.
`
`Please see accompanying full Prescribing Information for
`
`additional important safety information, including
`
`Boxed WARNINGS.
`
`KADCYLA Access Solutions
`
`@Kaclcgla‘i
`
`EClII-iIE-EiLEJVuiil flll'E'E ifl
`
`Access Solutions
`
`ICADCYLA Access Solutions helps to resolve access and
`
`reimbursement issues for individual patients every day. Our
`
`dedicated Specialists help bring patient treatment and
`
`practice solutions together.
`
`Our staff can:
`
`* Help confirm benefits and coverage and resolve any
`
`related issues
`
`1* Refer underinsured patients for co- pay assistance
`
`* Provide free medicine to qualified uninsured patients
`
`through the Genentech= Access to Care Foundation
`
`[GATE-F}
`
`* lndividualize services to meet your patients' specific
`
`needs
`
`New! Unique III—code is now available for ICADCYLA
`
`reimbursement. lIllick here for more information.
`
`To speak live with one of our Specialists, call
`
`1 {SEE} 249-4913. You can also visit Genentech-
`
`Access.comII£ADtIYLA for more information.
`
`Additional resources
`
`* Get HADEYLA Access Solutions information
`
`1* See the latest list of distributors
`
`* Download the IEADIIYLA Material Safety Data Sheet
`
`The ICADCYLA and Access Solutions logos are registered
`
`trademarks of Genentech, Inc.
`
`Genentech
`.'I
`.ilu'ruullr'l I
`_' Erin. JI'Jll-IL'
`':.-Illlr_l|
`
`This site is intended for US residents only.
`
`lLiontact Us I Site Map I Important Safety
`Home I
`Information I Privacy Policy I Terms and IlLionditionts
`
`iii 2313 Genentech USA, Inc. All rights reserved.
`
`IMMUNOGEN 2226. Pg. 8
`Phigenix v. lmmunogen
`lPR2014-00676
`
`8
`
`IMMUNOGEN 2226, pg. 8
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`a fin to Patients EL
`
`Ce regivers site
`
` This iafsrr‘fietisa is fer Heelthee re
`s ,Kadcyla
`.
`
`Frefe ssiefiels
`
`'1
`
`a.
`-\..--\.-
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`“Cl ”in; Eli"-
`
`+ Safety' first! Press here to read the
`Important Safety Information
`
`The first antibody-d rug eenjugate fer the
`
`metastatic breast ea neer [H BE]
`
`treatment of HERE-positive [HEH2+]
`
`a Learn more
`
`Trestuzumeb
`
`Imeneelenel entihed'ri'
`Binds te HEFi'E at subdemsin
`
`Wte suppress dewnstream
`signaling
`
`IMMUNOGEN 2226. pg. 9
`Phigenix v. Immunogen
`|PR2014-00676
`
`9
`
`IMMUNOGEN 2226, pg. 9
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`10
`
`Profs ssiooels
`
`:1 Go to Patients Er.
`
`Co regivers site
`
` This ioforr‘oetioo is for Heelthee re
`.19... {Kadcyla
`.
`
`'1
`
`a.
`-\..--\.-
`.II
`- ”II
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`*Jfl-i ‘* LI-‘l
`“Cl -="'io Eli"-
`
`¢ Safety first! Pro-I here to read the
`Important Safety Information
`
`The first antibody-cl rug conjugate for the
`
`l'I'IEtHE'
`
`Dlul1* [cytotoxic mo'lrtorlrsinoill'.l
`Inhibits tubulin polymerization to
`induce cell-cycle arrest and cell
`death
`
`
`
`It Learn more
`
`‘4'
`
`* Emte nsine is the combination "
`
`of DM1 _ a cytotoxic
`
`meyrtensinoid, end the stable
`MEI: linker.
`
`IMMUNOGEN 2226. Pg. 10
`Phigenix v. Immunogen
`|PR2014-00676
`
`10
`
`IMMUNOGEN 2226, pg. 10
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This ififarr‘wetiafi is far Heelthee re
`
`1: Ga ta Patients 31
`
`11
`
`Prefessiafiels
`
`Caregivers site
`19.. {Kadcyla
`.
`
`a.
`-\..--\.-
`- ”a ll
`.I.--\.II
`.-.I
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`.t_. H .t
`.5
`..
`‘Jfl-i ‘* LI”
`{I -="'ic HIV-
`
`+ Safety first! Press here to read the
`-
`Important Safety Information
`
`The first antibacly-cl rug ccnjugate far the
`
`treatment at HERE-pcsitive [HEH2+] metastatic
`
`after entering the targ at cell
`It Learn more
`
`* En'lta nsine is the
`
`combination at DM1 , a
`
`cflataxic n1ay1ansinaid,
`and the stable I'III'IEC
`
`breast cancer [H "‘3'?“ stable linker}
`Stabilizes KADC‘I'IJ'L in
`circulation ta release Dlul1
`
`
`
`IMMUNOGEN 2226.139. 11
`Phigenix v. Immunogen
`|PR2014-00676
`
`11
`
`IMMUNOGEN 2226, pg. 11
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for
`Healthcare1|2rofessionals
`
`EQKadcglai
`
`.
`
`ETJLI-i'EETLIELNEEI 9“"i-1“31FE
`
`:-:- Go to Patients 3:.
`|Sereg ivers site
`
`
`
`
`Safety first! Press here to read the
`
`Important Safety Information
`
`1ii'ieiir Proposed Mechanism ofAction
`
`Contact a Representative
`
`a Learn more about ltADE‘i'LA. Press below
`
`for an appointment with a clinical
`
`nLeiInmore
`
`oncologist specialisL
`
`lGontactus
`
`Tools & Resources
`
`:1 Dosing incl Administration Guide
`
`:1 Dose Mortification Worksheet
`
`:1 Medication Distinction Poster
`
`:1 Hurse—to—Patient Tear Sheet
`
`Glinical Data Available
`
`Review significant survival results and the
`
`adverse reaction profile demonstrated in the
`Phase III EMILIA b'ial.
`
`Indication
`
`KADG‘I'LAI "1 {ado—trastuzumab emtansine}, as
`
`a single agent, is indicated for the treabhent of
`
`patients with HER2—positive [HER2+}, metastatic
`
`breast cancer {MEG} who previously received
`
`trastuzumab and a taxane, separately or in
`
`combination. Patients should have either:
`
`1* Received prior therapy for metastatic
`
`disease, or
`
`* Developed disease recurrence during or
`
`within six months of completing adjuvant
`
`therapy
`
`Important Safety lnfonnation
`
`Boxed WARNINGS:
`
`HEPATDTDXICITV. CARDIAC;
`
`TII'LiKIGI'I'II‘Er EMBRVD-FETAL
`
`TDXIGITV
`
`* DoflotSubstitutellIADG‘t'LAfororwith
`
`Trastuzumab
`
`* Hepatotoxicity: Serious hepatotoxicity
`
`has been reported, including liver failure
`
`and death in patients treated with
`
`HADE'I'LA. Monitor semm transaminases
`
`and bilirubin plior to initiation of
`
`flADfl‘i’LA treatment and prior to each
`
`HADE‘PLA dose. Reduce dose or
`
`discontinue KADGVLA as appropriate in
`
`cases of increased semm transaminases
`
`or total bilimbin
`
`* Cardiac Toxicity: KADG‘H'LA
`
`administiation may lead to reductions in
`
`left ventiicular eieclion fraction {LVEH.
`
`Evaluate left ventricular function in all
`
`pafients plior to and during treatment
`
`with IEADITI'LA. 1Il'll'ithhold treatment for
`
`clinically significant decrease in left
`
`ventricular function
`
`* Embryo-Fetal Toxicity: Exposureto
`
`KADS'I'LA can resuft in embryo-fetal
`
`death or b'lth defects. Advise patients of
`
`these Iislcs and the need for effective
`
`contraception
`
`Additional Important Safety
`
`lnfonnation:
`
`Left Ven'b'icular Dysfulction IIH'D]
`
`* Patients treated with HADEYLA are at
`
`increased risl: of developing DID. In
`
`EMILIA, DID occurred in 1.5% of patients
`
`in the KADG‘I'LA—treated group and in
`
`3.3% in the ccmpa rator group.
`
`Permanently discontinue KADGYLA if
`
`L'ul'EF has not improved or has declined
`
`further
`
`Pregnancy Registry
`
`* Advise patients to contact their
`
`healthcare provider immediately if they
`
`suspect they may be pregnant.
`
`Encourage women who may be exposed
`
`to ICADC‘I'LA during pregnancy to enroll
`
`in the Ili‘lotHER Pregnancy Registry by
`
`contacting 1 [30m Still-622"
`
`Pulnonary Toxicity
`
`* Cases of interstitial lung disease [ILD},
`
`including pneumonitis, some leading to
`
`acute respiratory distress syndrome or
`
`fatal outcome have been reported in
`
`clinical trials with ICADC‘I'LA. In EMILIA,
`
`the overall frequency of pneumonitis was
`
`1.2%
`
`* Treatment with HADEYLA should be
`
`permanently discontinued in patients
`
`diagnosed with ILD or pneumonitis
`
`Infusion—Related Reactions. Hypersensitivity Reactions
`
`* Treatment with HADEYLA has not been
`
`studied in patients who had trastuzumab
`
`permanently discontinued due to
`
`infusion—related reactions IIRR} andior
`
`hypersensitivity reactions: treatment with
`
`KADCTLA is not recommended for these
`
`patients. In EMILIA, the overall frequency
`
`of IRRs in patients treated with EADGYLA
`
`was 1.4%
`
`* KADCTLA treatment should be
`
`interrupted in patients with severe IRS
`
`and permanently discontinued in the
`
`event of a life—threatening IRR. Patients
`
`should be closely monitored for IRS
`
`reactions, especially during the first
`
`infusion
`
`Thrombocytopenia
`
`* In EMILIA, the incidence of: Grade 3
`
`thrombccytopenia was 14.5% in the
`
`KADETLA—treated group and D.4% in the
`
`comparator group [overall incidence
`
`31.2% and 3.3%, respectively}
`
`* Monitor platelet counts prior to initiation
`
`of ICADC‘I'LA and prior to each KADCTLA
`
`dose. Institute dose modifications as
`
`appropriate
`
`flecrrotomici'ty
`
`* In EMILIA, the incidence of: Grade 3
`
`peripheral neu ropathy was 2.2% in the
`
`KADETLA—treated group and D.2% in the
`
`comparator group [overall incidence
`
`21.2% and 13.5%, respectively}
`
`* Monitor for signs or symptoms of
`
`neurotoxicity. KADGTLA should be
`
`temporarily discontinued in patients
`
`experiencing Grade 3 or 4 peripheral
`
`neuropathy until resolution to :1 Grade 2
`
`HR Testing
`
`* Detection of HER2 protein
`
`overexpression or gene amplification is
`
`necessary for selection of patients
`
`appropriate for KADGYLA. Perform using
`
`FDA approved tests by laboratories with
`
`demonstrated proficiency
`
`Exbavasation
`
`* In KADG‘I'LA clinical studies, reactions
`
`secondary to extravasation have been
`
`observed and were generally mild. The
`
`infusion site should be closely monitored
`
`for possible subcutaneous infiltration
`
`during drug administration. Specific
`
`treatment for KADCTLA extravasation is
`
`unknown
`
`I'llursing Mothers
`
`* Discontinue nursing or discontinue
`
`EADGYLA taking into consideration the
`
`importance of the drug to the mother
`
`Adverse Reactions
`
`* The most common ADRs seen with
`
`KADCTLA in EMILIA {frequency 3: 25%]
`
`were nausea, fatigue, musculoslreletal
`
`pain, thrombocytopenia, increased
`
`transaminases, headache, and
`
`constipation. The most common
`
`HGI—GTCAE [version 3:: 2 Grade 3 ADRs
`
`{frequency 2:- 2%} were
`
`thrombocytopenia, increased
`
`transaminases, anemia, hypo Iralemia,
`
`peripheral neuropathy and fatigue
`
`You are encouraged to report side effects to
`
`Genentech and the FDA. You may contact
`
`Genentech by calling 1 {333] 335-2555. 1'i"'ou may
`
`contact the FDA by visiting
`
`www.fda.gov!medwatch or calling
`
`1 [SW] HltA-tllfl.
`
`Please see accompanying full Prescribing
`
`Information for additional important safety
`
`information, inclucing Boxed 1illitARf‘illfiIGS.
`
`KADC‘t'LA Access Solutions
`
`@Kadcgla‘
`
`.,'.Il|':'._'.‘5i|_.-'.ll' ._'.,lfl'|'-:1'|5~|'I,'I
`
`Access Solutions
`
`KADG‘I'LA Access Solutions helps to resolve
`
`access and reimbursement issues for individual
`
`patients every day. Our dedicated Specialists
`
`help bring patient treabnent and practice
`
`solutions together.
`
`Dur staff can:
`
`* Help confirm benefits and coverage and
`
`resolve any related issues
`
`* Refer underinsu red patients for con-pay
`
`assistance
`
`* Provide free medicine to qualified
`
`uninsured patients through the
`
`Genentech: Access to lCare Foundation
`
`{GATGFI
`
`* Individuaize servicls to meet your
`
`patients’ specific needs
`
`New! Unique C—mde is now available for
`
`KADG‘I'LA reimbursement. Click here for more
`
`information.
`
`To spealc live with one of our Specialists, call
`
`1 [SE] 243-1913. 1it"ou can also visit Genentech-
`
`AccesscomfllIADG‘t'LA for more information.
`
`Additional resources
`
`* Get KADE‘VLA Access Solutions
`
`inforrnafion
`
`* See the latest fist of ristributors
`
`* Dowrload the KADGYLA Material Safety
`
`Data Sheet
`
`The ICADC‘I'LA and Access Solutions logos are
`
`registered trademarks of Genentech, Inc.
`
`Genentech
`
`Home I Contact Us I Site Map I Important Safety
`Infomtation I Plivacy Policy I Terms and l[londitions
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`This site is intended for US residents: only.
`
`£22: 2013 Gene ntech |._.|E§.A, Inc. All rights
`
`reserved.
`
`IMMUNOGEN 2226, pg. 12
`Phigenix v. Immunogen
`|PR2014-00676
`
`12
`
`IMMUNOGEN 2226, pg. 12
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthca re
`
`11 Eio to Patients 3:.
`
`13
`
`Professionals
`
`Caregivers site
` @Kadcyla"
`
`;:|:I-t';£'.LIEL”::I 3” Pairs
`
`Home
`
`About HADEVLA
`
`Clinical Information
`
`Dosing and Administration
`
`Resources
`
`Patient Support
`
`}
`
`}
`
`}
`
`}
`
`}
`
`.L
`
`J;
`
`Contact s_
`Representative
`
`Tools 3:
`Resources
`
`m:
`
`Register for
`Updates
`
`
`
`Contact Us | Prescribing
`
`Information | Important Safety
`
`Information | Privacy Policy | Terms and
`Conditions
`
`IMMUNOGEN 2226. Pg. 13
`Phigenix v. Immunogen
`|PR2014-00676
`
`13
`
`IMMUNOGEN 2226, pg. 13
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthca re
`
`Professionals
`
`11 El o to Patients 3:.
`
`
`
`Caregivers site
`
`.
`
`@Kadcyla“‘
`
`fi'fin- d.” n..--\.'-\.-\.
`.-.--\.r-
`.-.-.-
`'IJ-i-‘~U-'| 4* Huh
`
`Ho me-
`
`Ahout KADCYLA
`
`:-:- KADCVLA Structure
`
`:-:- Proposed MBA
`
`Elinical Information
`
`:-:- Trial Design
`
`':- Crverall survival
`
`Progression-tree survival
`
`':- Citijective response rate
`
`Duration of response
`
`:-:- Adverse reaction profile
`
`Dose reductions and treatment
`' discontinuaticns
`
`SUI‘I‘lI‘I‘lEIy of adverse reactions
`
`':- Important Eatetvr Information
`
`Dosing and Administration
`
`:-:- Preparing and Storing KADCVLA
`
`:-:- Administering KADCVLA
`
`Resources
`
`Eonditions
`
`:-:- Professional Ftesources and Downloads
`
`:-:- Contact a Ftepresentative
`
`Patient Support:
`
`:-=- Financial Support for Your Patients
`
`:-:- Patient Support Line
`
`1
`CDF‘IIEIEII El
`Ftepresentative
`
`i.
`TDUIS El.
`Ftescurces
`
`M
`Hegigter fur
`Updates
`
`Contact Us | Prescribing
`
`Information | Important Safety
`
`Information | Privacy Policy | Terms and
`
`IMMUNOGEN 2226. Pg. 14
`Phigenix v. Immunogen
`|PR2014-00676
`
`14
`
`IMMUNOGEN 2226, pg. 14
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`Fieview significant survival results and the adverse reaction
`profile défimnstrated in the Phase III EMILIA trial.
`
`a: Learn more
`
`
`
`Indication
`
`.sasingle
`-
`'
`.
`.
`_
`_
`HM}
`
`with HERE—
`
`
`[I] who
`
`_ separatelyr or
`
`ase, or
`
`
`months of completing adjuvant thera py'
`
`ithin six
`
`Important Safety Information
`
`Boxed WARNINGS: HEPATDTOXICITY,
`
`CARDIAC Tlfllu‘tflfllT‘I".r EMBRYO-FETAL
`
`TICIIIJKIIHT‘IF
`
`* Do hlot Substitute ILADIII‘I'LA for or with Trastuzumah
`
`* Hepatotoxieitf: Serious hepatoto‘.u.'i~c:itvllr has been
`
`reported, including liver failure and death in patients
`'lrnn'hu'l Iui'l'h Hfiml fl Hflnni'lnr enrllrn irnnenminnm
`
`IMMUNOGEN 2226, pg. 15
`Phigenix v. Immunogen
`lPR2014-00676
`
`15
`
`IMMUNOGEN 2226, pg. 15
`Phigenix v. Immunogen
`IPR2014-00676
`
`

`

`This information is for Healthcare
`
`16
`
`Professionals
`
`.
`
`@Kadcylai
`
`-
`.ln-‘Lr
`F.-
`.t_. .s
`s
`‘JCI-l “~ U”
`
`I'l-
`'LF'I.‘
`I'I
`Ill-III
`.
`s
`..
`.t
`{Iii-.1 *Il'c
`
`Go to Patients 3'.
`
`Caregivers site
`
`
`
`
`Safety first! Press here to read the
`
`Important Safety lnformat ion
`
`The first antibcdg-drug conjugate for the
`
`treatment of HERE-positive [H EHE+]
`
`metastatic breast cancer [MEIC]
`
`a Learn more
`
`Page Name: HCP Homepage
`Page Title: KADCYLA® (ado-trastuzumab emtansine) Information for
`Healthcare Professionals
`
`Meta Description: Find information for healthcare professionals about
`KADCYLA® (ado-trastuzumab emtansine), a treatment for HER2-positive
`metastatic breast cancer patients.
`KADCYLA® (ado-trastuzumab emtansine), injection for intravenous use, as a
`single agent, is indicated for the treatment of patients with HER2-positive
`(HER2+), metastatic breast cancer (MBC) who previously received
`trastuzumab and a taxane, separately or in combination. Patients should have
`either: Received prior therapy for metastatic disease, or Developed disease
`recurrence during or within six months of completing adjuvant therapy.
`Important Safety Information: Boxed WARNINGS: HEPATOTOXICITY,
`CARDIAC TOXICITY, EMBRYOFETAL TOXICITY: Do Not Substitute
`
`KADCYLA for or with Trastuzumab, Hepatotoxicity: Serious hepatotoxicity has
`been reported, including liver failure and death in patients treated with
`KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of
`KADCYLA treatment and prior to each. KADCYLA dose. Reduce dose or
`discontinue KADCYLA as appropriate in cases of increased serum
`transaminases or total bilirubin, Cardiac Toxicity: KADCYLA administration
`may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left
`ventricular function in all patients prior to and during treatment with KADCYLA.
`Withhold treatment for clinically significant decrease in left ventricular function,
`Embryo-Fetal Toxicity: Exposure to KADCYLA can result in embryo-fetal death
`or birth defects. Advise patients of these risks and the need for effective
`contraception. The following additional serious adverse reactions have been
`reported in clinical trials with KADCYLA: Interstitial Lung Disease (ILD),
`including pneumonitis, some leading to acute respiratory distress syndrome or
`fatality: KADCYLA should be permanently discontinued in patients diagnosed
`with ILD or pneumonitis, Infusion-related reactions (IRR), Hypersensitivity:
`KADCYLA treatment should be interrupted in patients with severe IRR and
`permanently discontinued in the event of a life-threatening IRR,
`Thrombocytopenia: Monitor platelet counts prior to initiation of KADCYLA and
`prior to each dose. Institute dose modifications as appropriate, Peripheral
`neuropathy: KADCYLA should be temporarily discontinued in patients
`experiencing Grade 3 or 4 peripheral neuropathy until resolution to S Grade 2,
`Reactions secondary to extravasation: The infusion site should be closely
`monitored for possible subcutaneous infiltration during drug administration.
`Additional Important Safety Information: Detection of HER2 protein
`overexpression or gene amplification is necessary for selection of patients
`appropriate for KADCYLA therapy, Nursing mothers: Discontinue nursing or
`discontinue KADCYLA taking into consideration the importance of the drug to
`the mother, The most common adverse drug reactions (frequency > 25%)
`across clinical trials with KADCYLA were fatigue, nausea, musculoskeletal
`pain, thrombocytopenia, headache, increased transaminases, and
`constipation. You are encouraged to report side effects to Genentech and the
`FDA Ymr mm/ nnntqnt Gnnnntnnh hv nailinn 1_RRR_RRFI_7FIFIFI Ymr mm/ nnntqnt
`
`Review significant survival results and the adverse
`
`reaction profile demonstrated in the Phase III EMILIA
`trial-
`
`Indication
`
`KADG‘fLA3 "1 [ado—trastuzumab emtansine}, as a
`single agent, is indicated for the treatment of
`
`patients with HER2—positive [HER2+',I, metastatic
`
`breast cancer [MBGI who previously received
`
`trastuzumab and a taxane, separately or in
`
`combination. Patients should have either:
`
`1* Received prior therapy for metastatic disease,
`or
`
`1* Developed disease recurrence during or
`
`within six months of completing adjuvant
`
`therapy
`
`Important Safety Information
`
`Boxed WARNINGS:
`
`HEPATIIIITIIIIIrllltlilT'li‘llr CARDIAC
`
`TtIIIIII'lIItIIIT"'I"'.r EMBR‘I’D-FEI'AL T'IIIIIIIIIII'IIIIT‘II“r
`
`1* Do Not Substitute KADCYLA for or with
`
`Trastuzu mab
`
`* Hepatotoxicity: Serious hepatotoxicity has
`
`been reported, including liver failure and
`
`death in patients treated with IEADG‘I'LA.
`
`Monitor serum transaminases and bilirubin
`
`prior to initiation of KADCYLA treatment and
`
`prior to each KADCYLA dose. Reduce dose or
`
`discontinue KADCYLA as appropriate in cases
`
`of increased serum transaminases or total
`
`bilirubin
`
`* lGardiac Toxicity: IEADIIYLA administration
`
`may lead to reductions in left ventricular
`
`ejection fraction [LVEFL Evaluate left
`
`ventricular function in all patients prior to and
`
`during treatm