HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`POMALYST safely and effectively. See full prescribing information for
`POMALYST.
`
`POMALYST® (pomalidomide) capsules, for oral use
`Initial U.S. Approval: 2013
`
`WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND
`ARTERIAL THROMBOEMBOLISM
`See full prescribing information for complete boxed warning
`EMBRYO-FETAL TOXICITY
`POMALYST is contraindicated in pregnancy. POMALYST is a
`
`thalidomide analogue. Thalidomide is a known human teratogen
`that causes severe life-threatening birth defects (4, 5.1, 8.1).
`For females of reproductive potential: Exclude pregnancy before
`start of treatment. Prevent pregnancy during treatment by the use
`of 2 reliable methods of contraception (5.1, 8.3).
`POMALYST is available only through a restricted program called
`POMALYST REMS® (5.2).
`
`
`
`VENOUS AND ARTERIAL THROMBOEMBOLISM
` Deep venous thrombosis (DVT), pulmonary embolism (PE),
`myocardial infarction, and stroke occur in patients with multiple
`myeloma treated with POMALYST. Antithrombotic prophylaxis is
`recommended (5.3).
`
`--------------------------RECENT MAJOR CHANGES----------------------------
`
`Warnings and Precautions (5.1, 5.4, 5.7)
`
`03/18
`
`---------------------------INDICATIONS AND USAGE----------------------------
`POMALYST is a thalidomide analogue indicated, in combination with
`dexamethasone, for patients with multiple myeloma who have received at
`least two prior therapies including lenalidomide and a proteasome inhibitor
`and have demonstrated disease progression on or within 60 days of
`completion of the last therapy (1.1).
`
`-----------------------DOSAGE AND ADMINISTRATION-----------------------
`Multiple Myeloma: 4 mg per day taken orally on Days 1-21 of repeated 28-
`day cycles until disease progression (2.1). Refer to section 14.1 for
`dexamethasone dosing (14.1)
`
`----------------------DOSAGE FORMS AND STRENGTHS--------------------
`Capsules: 1 mg, 2 mg, 3 mg, and 4 mg (3)
`
`-------------------------------CONTRAINDICATIONS------------------------------
`Pregnancy (4)
`
`
`
`
`
`
`
`
`-----------------------WARNINGS AND PRECAUTIONS-----------------------
`Increased Mortality: Observed in patients with multiple myeloma when
`
`pembrolizumab was added to dexamethasone and a thalidomide
`analogue (5.4).
`Hematologic Toxicity: Neutropenia was the most frequently reported
`Grade 3/4 adverse event. Monitor patients for hematologic toxicities,
`especially neutropenia (5.5).
`Hepatotoxicity: Hepatic failure including fatalities; monitor liver
`function tests monthly (5.6).
`Severe Cutaneous Reactions Including Hypersensitivity Reactions:
`Angioedema and severe cutaneous reactions including Stevens-Johnson
`syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia
`and systemic symptoms have been reported. Discontinue POMALYST
`for angioedema and severe reactions (5.7).
`Tumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e.,
`those with high tumor burden) and take appropriate precautions (5.11).
`
`
`
`-------------------------------ADVERSE REACTIONS------------------------------
`Most common adverse reactions (≥30%) included fatigue and asthenia,
`neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-
`respiratory tract infections, back pain, and pyrexia (6.1).
`
`To report SUSPECTED ADVERSE REACTIONS, contact Celgene
`Corporation at 1-888-423-5436 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`--------------------------------DRUG INTERACTIONS-----------------------------
`Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2
`inhibitors. If a strong CYP1A2 inhibitor must be used, reduce POMALYST
`dose by 50% (2.3, 7.1, 12.3).
`
`--------------------------USE IN SPECIFIC POPULATIONS---------------------
`Lactation: Advise women not to breastfeed (8.2).
`
`Renal Impairment: Reduce POMALYST dose by at least 25% in
`
`patients with severe renal impairment requiring dialysis. Take dose
`of POMALYST following hemodialysis on hemodialysis days
`(2.4, 8.6).
`Hepatic Impairment: Reduce POMALYST dose by 25% in patients
`with mild to moderate hepatic impairment, reduce POMALYST
`dose by 50% in patients with severe hepatic impairment (2.5, 8.7).
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`Revised: 05/2018
`
`ALVOGEN, Exh. 1027, p. 0001
`
`

`

`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`2
`
`3
`4
`
`WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND
`ARTERIAL THROMBOEMBOLISM
`1
`INDICATIONS AND USAGE
`1.1 Multiple Myeloma
`DOSAGE AND ADMINISTRATION
`2.1 Multiple Myeloma
`2.2 Dose Adjustments for Toxicities
`2.3 Dosage Adjustment for Strong CYP1A2 Inhibitors
`2.4 Dosage Adjustment for Patients with Severe Renal Impairment on
`Hemodialysis
`2.5 Dosage Adjustment for Patients with Hepatic Impairment
`DOSAGE FORMS AND STRENGTHS
`CONTRAINDICATIONS
`Pregnancy
`5 WARNINGS AND PRECAUTIONS
`5.1 Embryo-Fetal Toxicity
`5.2 POMALYST REMS Program
`5.3 Venous and Arterial Thromboembolism
`5.4
`Increased Mortality in Patients with Multiple Myeloma When
`Pembrolizumab Is Added to a Thalidomide Analogue and
`Dexamethasone
`5.5 Hematologic Toxicity
`5.6 Hepatotoxicity
`5.7 Severe Cutaneous Reactions Including Hypersensitivity Reactions
`5.8 Dizziness and Confusional State
`5.9 Neuropathy
`5.10 Risk of Second Primary Malignancies
`5.11 Tumor Lysis Syndrome
`ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`
`6
`
`8
`
`7
`
`6.2 Postmarketing Experience
`DRUG INTERACTIONS
`7.1 Drugs That Affect Pomalidomide Plasma Concentrations
`USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.3 Females and Males of Reproductive Potential
`8.4 Pediatric Use
`8.5 Geriatric Use
`8.6 Renal Impairment
`8.7 Hepatic Impairment
`8.8 Smoking Tobacco
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`14 CLINICAL STUDIES
`14.1 Multiple Myeloma
`15 REFERENCES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Storage
`16.3 Handling and Disposal
`PATIENT COUNSELING INFORMATION
`17
`*Sections or subsections omitted from the full prescribing information are not
`listed.
`
`ALVOGEN, Exh. 1027, p. 0002
`
`

`

`FULL PRESCRIBING INFORMATION
`
`WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM
`
`Embryo-Fetal Toxicity
` POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is
`a known human teratogen that causes severe birth defects or embryo-fetal death. In females of
`reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.
` Females of reproductive potential must use 2 forms of contraception or continuously abstain from
`heterosexual sex during and for 4 weeks after stopping POMALYST treatment [see Contraindications
`(4), Warnings and Precautions (5.1), and Use in Specific Populations (8.1, 8.3)].
`POMALYST is only available through a restricted distribution program called POMALYST REMS [see
`Warnings and Precautions (5.2)].
`Venous and Arterial Thromboembolism
` Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in
`patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were
`employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be
`based on assessment of the patient's underlying risk factors [see Warnings and Precautions (5.3)].
`
`1 INDICATIONS AND USAGE
`
`1.1 Multiple Myeloma
`POMALYST, in combination with dexamethasone, is indicated for patients with multiple myeloma who have
`received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated
`disease progression on or within 60 days of completion of the last therapy.
`
`2 DOSAGE AND ADMINISTRATION
`
`2.1 Multiple Myeloma
`Females of reproductive potential must have negative pregnancy testing and use contraception methods before
`initiating POMALYST [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].
`
`The recommended starting dose of POMALYST is 4 mg once daily orally on Days 1-21 of repeated 28-day
`cycles until disease progression. POMALYST should be given in combination with dexamethasone [see
`Clinical Studies (14.1)].
`
`POMALYST may be taken with water. Inform patients not to break, chew, or open the capsules. POMALYST
`may be taken with or without food.
`
`ALVOGEN, Exh. 1027, p. 0003
`
`

`

`2.2 Dose Adjustments for Toxicities
`
`Toxicity
`
`Table 1:Dose Modification Instructions for POMALYST for Hematologic Toxicities
`Dose Modification
`
`Neutropenia
` ANC <500 per mcL or febrile neutropenia (fever
`more than or equal to 38.5°C and ANC <1,000
`per mcL)
`
` ANC return to more than or equal to 500 per
`mcL
`
` Interrupt POMALYST treatment, follow CBC weekly
`
` Resume POMALYST treatment at 3 mg daily
`
` For each subsequent drop <500 per mcL
`
` Interrupt POMALYST treatment
`
` Return to more than or equal to 500 per mcL
`
` Resume POMALYST treatment at 1 mg less than the
`previous dose
`
`Thrombocytopenia
` Platelets <25,000 per mcL
`
` Interrupt POMALYST treatment, follow CBC weekly
`
` Platelets return to >50,000 per mcL
`
` Resume POMALYST treatment at 3 mg daily
`
` For each subsequent drop <25,000 per mcL
`
` Interrupt POMALYST treatment
`
` Return to more than or equal to 50,000 per mcL
`
` Resume POMALYST treatment at 1 mg less than
`previous dose
`
`ANC, absolute neutrophil count
`
`To initiate a new cycle of POMALYST, the neutrophil count must be at least 500 per mcL and the platelet
`count must be at least 50,000 per mcL. If toxicities occur after dose reductions to 1 mg, then discontinue
`POMALYST.
`
`Permanently discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe
`dermatologic reaction [see Warnings and Precautions (5.7)].
`
`For other Grade 3 or 4 toxicities, hold treatment and restart treatment at 1 mg less than the previous dose when
`toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion.
`
`2.3 Dosage Adjustment for Strong CYP1A2 Inhibitors
`Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a
`strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50% [see Drug Interactions (7.1) and
`Clinical Pharmacology (12.3)].
`
`2.4 Dosage Adjustment for Patients with Severe Renal Impairment on Hemodialysis
`For patients with severe renal impairment requiring dialysis, the recommended starting dose is 3 mg daily (25%
`dose reduction). Take POMALYST after completion of dialysis procedure on hemodialysis days [see Use in
`Specific Populations (8.6) and Clinical Pharmacology (12.3)].
`
`2.5 Dosage Adjustment for Patients with Hepatic Impairment
`For patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), the recommended starting
`dose is 3 mg daily (25% dose reduction). For patients with severe hepatic impairment (Child-Pugh class C), the
`
`ALVOGEN, Exh. 1027, p. 0004
`
`

`

`recommended dose is 2 mg (50% dose reduction) [see Use in Specific Populations (8.7) and Clinical
`Pharmacology (12.3)].
`
`
`
`3 DOSAGE FORMS AND STRENGTHS
`POMALYST is available in the following capsule strengths:
`1 mg: Dark blue opaque cap and yellow opaque body, imprinted “POML” on the cap in white ink and “1
`
`mg” on the body in black ink
`2 mg: Dark blue opaque cap and orange opaque body, imprinted “POML” on the cap and “2 mg” on the
`body in white ink
`3 mg: Dark blue opaque cap and green opaque body, imprinted “POML” on the cap and “3 mg” on the
`body in white ink
`4 mg: Dark blue opaque cap and blue opaque body, imprinted “POML” on the cap and “4 mg” on the
`body in white ink
`
`
`
`
`
`4 CONTRAINDICATIONS
`
`Pregnancy
`POMALYST can cause fetal harm when administered to a pregnant female [see Warnings and Precautions
`(5.1) and Use in Specific Populations (8.1)]. POMALYST is contraindicated in females who are pregnant.
`Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during
`the period of organogenesis. If this drug is used during pregnancy or if the patient becomes pregnant while
`taking this drug, the patient should be apprised of the potential risk to a fetus.
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Embryo-Fetal Toxicity
`POMALYST is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a
`known human teratogen that causes severe birth defects or embryo-fetal death [see Use in Specific Populations
`(8.1)]. POMALYST is only available through the POMALYST REMS program [see Warnings and Precautions
`(5.2)].
`
`Females of Reproductive Potential
`Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning POMALYST
`therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy.
`
`Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods
`of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy,
`during dose interruptions, and continuing for 4 weeks following discontinuation of POMALYST therapy.
`
`Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed
`within 10-14 days and the second test within 24 hours prior to prescribing POMALYST therapy and then
`weekly during the first month, then monthly thereafter in females with regular menstrual cycles, or every 2
`weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3)].
`
`Males
`Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex
`or synthetic condom during any sexual contact with females of reproductive potential while taking
`
`ALVOGEN, Exh. 1027, p. 0005
`
`

`

`POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful
`vasectomy. Male patients taking POMALYST must not donate sperm [see Use in Specific Populations (8.3)].
`
`Blood Donation
`Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation
`of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to
`POMALYST.
`
`5.2 POMALYST REMS Program
`Because of the embryo-fetal risk [see Warnings and Precautions (5.1)], POMALYST is available only through
`a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the “POMALYST REMS”
`program.
`
`Required components of the POMALYST REMS program include the following:
` Prescribers must be certified with the POMALYST REMS program by enrolling and complying with the
`REMS requirements.
` Patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements. In
`particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy
`testing and contraception requirements [see Use in Specific Populations (8.3)] and males must comply with
`contraception requirements [see Use in Specific Populations (8.3)].
` Pharmacies must be certified with the POMALYST REMS program, must only dispense to patients who are
`authorized to receive POMALYST and comply with REMS requirements.
`
`Further information about the POMALYST REMS program is available at www.celgeneriskmanagement.com
`or by telephone at 1-888-423-5436.
`
`5.3 Venous and Arterial Thromboembolism
`Venous thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial
`thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with
`POMALYST. In Trial 2, where anticoagulant therapies were mandated, thromboembolic events occurred in
`8.0% of patients treated with POMALYST and low dose-dexamethasone (Low-dose Dex), and 3.3% of patients
`treated with high-dose dexamethasone. Venous thromboembolic events (VTE) occurred in 4.7% of patients
`treated with POMALYST and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone.
`Arterial thromboembolic events include terms for arterial thromboembolic events, ischemic cerebrovascular
`conditions, and ischemic heart disease. Arterial thromboembolic events occurred in 3.0% of patients treated
`with POMALYST and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone.
`
`Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken
`to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is
`recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.
`5.4 Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a
`Thalidomide Analogue and Dexamethasone
`In two randomized clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a
`thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated,
`resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking
`antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of
`controlled clinical trials.
`
`ALVOGEN, Exh. 1027, p. 0006
`
`

`

`5.5 Hematologic Toxicity
`In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, neutropenia was the most frequently
`reported Grade 3/4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was
`reported in 51% of patients in both trials. The rate of Grade 3/4 neutropenia was 46%. The rate of febrile
`neutropenia was 8%.
`
`Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood counts weekly for
`the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification [see
`Dosage and Administration (2.2)].
`
`5.6 Hepatotoxicity
`Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of
`alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor
`liver function tests monthly. Stop POMALYST upon elevation of liver enzymes and evaluate. After return to
`baseline values, treatment at a lower dose may be considered.
`
`5.7 Severe Cutaneous Reactions Including Hypersensitivity Reactions
`Angioedema and severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal
`necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.
`DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever,
`and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis,
`and/or pericarditis. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe
`cutaneous reactions such as SJS, TEN or DRESS, and do not resume therapy [see Dosage and Administration
`(2.2)].
`
`5.8 Dizziness and Confusional State
`In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 14% of patients experienced dizziness
`and 7% of patients experienced a confusional state; 1% of patients experienced Grade 3 or 4 dizziness, and 3%
`of patients experienced Grade 3 or 4 confusional state. Instruct patients to avoid situations where dizziness or
`confusional state may be a problem and not to take other medications that may cause dizziness or confusional
`state without adequate medical advice.
`
`5.9 Neuropathy
`In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 18% of patients experienced
`neuropathy, with approximately 12% of the patients experiencing peripheral neuropathy. Two percent of
`patients experienced Grade 3 neuropathy in trial 2. There were no cases of Grade 4 neuropathy adverse
`reactions reported in either trial.
`
`5.10 Risk of Second Primary Malignancies
`Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an
`investigational therapy outside of multiple myeloma.
`
`5.11 Tumor Lysis Syndrome
`Tumor lysis syndrome (TLS) may occur in patients treated with pomalidomide. Patients at risk for TLS are
`those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate
`precautions taken.
`
`ALVOGEN, Exh. 1027, p. 0007
`
`

`

`6 ADVERSE REACTIONS
`The following adverse reactions are described in detail in other labeling sections:
` Fetal Risk [see Boxed Warning, Warnings and Precautions (5.1, 5.2)]
` Venous and Arterial Thromboembolism [see Boxed Warning, Warnings and Precautions (5.3)]
`Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a
`
`Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4)]
` Hematologic Toxicity [see Warnings and Precautions (5.5)]
` Hepatotoxicity [see Warnings and Precautions (5.6)]
` Severe Cutaneous Reactions Including Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
` Dizziness and Confusional State [see Warnings and Precautions (5.8)]
` Neuropathy [see Warnings and Precautions (5.9)]
` Risk of Second Primary Malignancies [see Warnings and Precautions (5.10)]
` Tumor Lysis Syndrome [see Warnings and Precautions (5.11)]
`
`6.1 Clinical Trials Experience
`Multiple Myeloma
`Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
`clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not
`reflect the rates observed in practice.
`
`In Trial 1, data were evaluated from 219 patients (safety population) who received treatment with POMALYST
`+ Low-dose Dex (112 patients) or POMALYST alone (107 patients). Median number of treatment cycles was 5.
`Sixty-seven percent of patients in the study had a dose interruption of either drug due to adverse reactions.
`Forty-two percent of patients in the study had a dose reduction of either drug due to adverse reactions. The
`discontinuation rate due to adverse reactions was 11%.
`
`In Trial 2, data were evaluated from 450 patients (safety population) who received treatment with POMALYST
`+ Low-dose Dex (300 patients) or High-dose Dexamethasone (High-dose Dex) (150 patients). The median
`number of treatment cycles for the POMALYST + Low-dose Dex arm was 5. In the POMALYST + Low-dose
`Dex arm, 67% of patients had a dose interruption of POMALYST, the median time to the first dose interruption
`of POMALYST was 4.1 weeks. Twenty-seven percent of patients had a dose reduction of POMALYST, the
`median time to the first dose reduction of POMALYST was 4.5 weeks. Eight percent of patients discontinued
`POMALYST due to adverse reactions.
`
`Tables 2 and 3 summarize the adverse reactions reported in Trials 1 and 2, respectively.
`
`Table 2: Adverse Reactions in Any POMALYST Treatment Arm in Trial 1*
`All Adverse Reactions ≥10% in
`Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`112 (100)
`
`Grade 3 or 4 ≥5% in Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`102 (91.1)
`
`POMALYST
`(N=107)
`98 (91.6)
`
`POMALYSTa
`(N=107)
`107 (100)
`
`Body System
`Adverse Reaction
`Number (%) of patients
`with at least one adverse
`reaction
`Blood and lymphatic
`system disorders
`
`ALVOGEN, Exh. 1027, p. 0008
`
`

`

`All Adverse Reactions ≥10% in
`Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`55 (49.1)
`47 (42.0)
`26 (23.2)
`22 (19.6)
`<10%
`17 (15.2)
`
`POMALYSTa
`(N=107)
`57 (53.3)
`41 (38.3)
`28 (26.2)
`14 (13.1)
` <10%
`4 (3.7)
`
`Grade 3 or 4 ≥5% in Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`46 (41.1)
`24 (21.4)
`21 (18.8)
`11 (9.8)
`3 (2.7)
`8 (7.1)
`
`POMALYST
`(N=107)
`51 (47.7)
`25 (23.4)
` 24 (22.4)
`7 (6.5)
`6 (5.6)
`2 (1.9)
`
`62 (57.9)
`27 (25.2)
`25 (23.4)
`11 (10.3)
`
`39 (36.4)
`38 (35.5)
`37 (34.6)
`15 (14.0)
`
`37 (34.6)
`25 (23.4)
`
`23 (21.5)
`18 (16.8)
`15 (14.0)
`13 (12.1)
`13 (12.1)
` 8 (7.5)
`
`70 (62.5)
`19 (17.0)
`36 (32.1)
`14 (12.5)
`
`27 (24.1)
`41 (36.6)
`40 (35.7)
`16 (14.3)
`
`36 (32.1)
`22 (19.6)
`
`22 (19.6)
`17 (15.2)
`15 (13.4)
` 8 (7.1)
`19 (17.0)
`16 (14.3)
`
`13 (12.1)
`0 (0.0)
` <5%
`0 (0.0)
`
`<5%
`<5%
`<5%
`<5%
`
`15 (14.0)
`<5%
`
`<5%
`<5%
`6 (5.6)
`<5%
`<5%
`0 (0.0)
`
`19 (17.0)
`0 (0.0)
`<5%
`0 (0.0)
`
`<5%
`<5%
`<5%
`0 (0.0)
`
`11 (9.8)
`0 (0.0)
`
`<5%
`<5%
`4 (3.6)
`<5%
`<5%
`<5%
`
`Body System
`Adverse Reaction
`Neutropenia b
`Anemia b
`Thrombocytopenia b
`Leukopenia
`Febrile neutropenia b
`Lymphopenia
`General disorders and
`administration site
`conditions
`Fatigue and asthenia b
`Edema peripheral
`Pyrexia b
`Chills
`Gastrointestinal
`disorders
`Nausea b
`Constipation b
`Diarrhea
`Vomiting b
`Musculoskeletal and
`connective tissue
`disorders
`Back pain b
`Musculoskeletal chest
`pain
`Muscle spasms
`Arthralgia
`Muscular weakness
`Bone pain
`Musculoskeletal pain
`Pain in extremity
`Infections and
`infestations
`
`ALVOGEN, Exh. 1027, p. 0009
`
`

`

`All Adverse Reactions ≥10% in
`Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`32 (28.6)
`
`POMALYSTa
`(N=107)
`40 (37.4)
`
`Grade 3 or 4 ≥5% in Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`<5%
`
`POMALYST
`(N=107)
`<5%
`
`30 (28.0)
`11 (10.3)
` <10%
`
`25 (23.4)
`23 (21.5)
`13 (12.1)
`12 (11.2)
`12 (11.2)
` <10%
` 6 (5.6)
`
`38 (35.5)
`18 (16.8)
`18 (16.8)
`10 (9.3)
`6 (5.6)
`
`24 (22.4)
`23 (21.5)
`16 (15.0)
`11 (10.3)
`
`22 (20.6)
`16 (15.0)
`10 (9.3)
`8 (7.5)
`
`38 (33.9)
`19 (17.0)
`<10%
`
`21 (18.8)
`13 (11.6)
`13 (11.6)
`17 (15.2)
`14 (12.5)
` <10%
`13 (11.6)
`
`50 (44.6)
`25 (22.3)
`12 (10.7)
`14 (12.5)
`12 (10.7)
`
`20 (17.9)
`20 (17.9)
`15 (13.4)
`15 (13.4)
`
`18 (16.1)
`10 (8.9)
`12 (10.7)
`18 (16.1)
`
`21 (19.6)
`2 (1.9)
`6 (5.6)
`
`<5%
`11 (10.3)
`<5%
`<5%
`<5%
`5 (4.7)
`0 (0.0)
`
`8 (7.5)
`0 (0.0)
`<5%
`0 (0.0)
`0 (0.0)
`
`<5%
`0 (0.0)
`0 (0.0)
`0 (0.0)
`
`0 (0.0)
`0 (0.0)
`0 (0.0)
`0 (0.0)
`
`32 (28.6)
`10 (8.9)
`5 (4.5)
`
`0 (0.0)
`1 (0.9)
`<5%
`<5%
`<5%
`6 (5.4)
`<5%
`
`14 (12.5)
`0 (0.0)
`0 (0.0)
`0 (0.0)
`0 (0.0)
`
`<5%
`0 (0.0)
`<5%
`0 (0.0)
`
`<5%
`0 (0.0)
`0 (0.0)
`0 (0.0)
`
`Body System
`Adverse Reaction
`Upper respiratory tract
`infection
`Pneumonia b
`Urinary tract infection b
`Sepsis b
`Metabolism and nutrition
`disorders
`Decreased appetite
`Hypercalcemia b
`Hypokalemia
`Hyperglycemia
`Hyponatremia
`Dehydration b
`Hypocalcemia
`Respiratory, thoracic and
`mediastinal disorders
`Dyspnea b
`Cough
`Epistaxis
`Productive cough
`Oropharyngeal pain
`Nervous system disorders
`Dizziness
`Peripheral neuropathy
`Headache
`Tremor
`Skin and subcutaneous
`tissue disorders
`Rash
`Pruritus
`Dry skin
`Hyperhidrosis
`
`ALVOGEN, Exh. 1027, p. 0010
`
`

`

`All Adverse Reactions ≥10% in
`Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`14 (12.5)
`
`POMALYSTa
`(N=107)
`5 (4.7)
`
`20 (18.7)
`
`11 (9.8)
`
`16 (15.0)
`1 (0.9)
`
`14 (13.1)
`13 (12.1)
`7 (6.5)
`
`10 (8.9)
`12 (10.7)
`
`8 (7.1)
`15 (13.4)
`18 (16.1)
`
`Grade 3 or 4 ≥5% in Either Arm
`POMALYST +
`Low-dose Dex
`(N=112)
`0 (0.0)
`
`POMALYST
`(N=107)
`0 (0.0)
`
`6 (5.6)
`
`0 (0.0)
`0 (0.0)
`
`0 (0.0)
`6 (5.6)
`0 (0.0)
`
`3 (2.7)
`
`0 (0.0)
`0 (0.0)
`
`0 (0.0)
`3 (2.7)
`0 (0.0)
`
`Body System
`Adverse Reaction
`Night sweats
`Investigations
`Blood creatinine
`increased b
`Weight decreased
`Weight increased
`Psychiatric disorders
`Anxiety
`Confusional state b
`Insomnia
`Renal and urinary
`disorders
`16 (15.0)
`Renal failure b
`* Regardless of attribution of relatedness to POMALYST.
`a POMALYST alone arm includes all patients randomized to the POMALYST alone arm who took study drug; 61 of the 107 patients had dexamethasone
`added during the treatment period.
`b Serious adverse reactions were reported in at least 2 patients in any POMALYST treatment arm.
`Data cutoff: 01 March 2013
`
`11 (9.8)
`
`9 (8.4)
`
`8 (7.1)
`
`Table 3:Adverse Reactions in Trial 2
`All Adverse Reactions
`(≥5% in POMALYST + Low-dose
`Dex arm, and at least 2% points
`higher than the High-dose-Dex arm)
`
`POMALYST +
`Low-dose Dex
`(N=300)
`297 (99.0)
`
`High-dose Dex
`(N=150)
`149 (99.3)
`
`Grade 3 or 4
`(≥1% in POMALYST + Low-dose
`Dex arm, and at least 1% point higher
`than the High-dose-Dex arm)
`POMALYST +
`Low-dose Dex
`(N=300)
`259 (86.3)
`
`High-dose Dex
`(N=150)
`127 (84.7)
`
`154 (51.3)
`89 (29.7) a
`38 (12.7)
`28 (9.3)
`
`31 (20.7)
`44 (29.3) a
`8 (5.3)
`0 (0.0)
`
`145 (48.3)
`66 (22.0) a
`27 (9.0)
`28 (9.3)
`
`24 (16.0)
`39 (26.0) a
`5 (3.3)
`0 (0.0)
`
`Body System
`Adverse Reaction
`Number (%) of patients with at
`least one adverse reaction
`Blood and lymphatic system
`disorders
`Neutropenia b
`Thrombocytopenia
`Leukopenia
`Febrile neutropenia b
`General disorders and
`administration site conditions
`
`ALVOGEN, Exh. 1027, p. 0011
`
`

`

`All Adverse Reactions
`(≥5% in POMALYST + Low-dose
`Dex arm, and at least 2% points
`higher than the High-dose-Dex arm)
`
`POMALYST +
`Low-dose Dex
`(N=300)
`140 (46.7)
`80 (26.7)
`52 (17.3)
`11 (3.7) a
`
`High-dose Dex
`(N=150)
`64 (42.7)
`35 (23.3)
`17 (11.3)
`3 (2.0) a
`
`Grade 3 or 4
`(≥1% in POMALYST + Low-dose
`Dex arm, and at least 1% point higher
`than the High-dose-Dex arm)
`POMALYST +
`Low-dose Dex
`(N=300)
`26 (8.7) a
`9 (3.0) a
`4 (1.3) a
`5 (1.7)
`
`High-dose Dex
`(N=150)
`18 (12.0) a
`7 (4.7) a
`3 (2.0) a
`1 (0.7)
`
`93 (31.0)
`
`19 (12.7)
`
`9 (3.0)
`
`1 (0.7)
`
`58 (19.3)
`3 (1.0) a
`
`66 (22.0)
`65 (21.7)
`45 (15.0)
`23 (7.7)
`
`59 (19.7)
`54 (18.0)
`46 (15.3)
`26 (8.7)
`20 (6.7) a
`
`76 (25.3)
`60 (20.0)
`5 (1.7) a
`
`52 (17.3)
`37 (12.3)
`23 (7.7)
`
`20 (13.3)
`0 (0.0) a
`
`28 (18.7)
`22 (14.7)
`17 (11.3)
` 6 (4.0)
`
`24 (16.0)
`21 (14.0)
`11 (7.3)
` 7 (4.7)
` 9 (6.0) a
`
`25 (16.7)
`15 (10.0)
`0 (0.0) a
`
`18 (12.0)
`14 (9.3)
`8 (5.3)
`
`47 (15.7)
`3 (1.0)
`
`3 (1.0) a
`7 (2.3)
`3 (1.0) a
`3 (1.0)
`
`15 (5.0)
`22 (7.3)
`1 (0.3) a
`2 (0.7) a
`6 (2.0)
`
`17 (5.7)
`2 (0.7) a
`4 (1.3)
`
`5 (1.7) a
`4 (1.3) a
`1 (0.3) a
`
`15 (10.0)
`0 (0.0)
`
`2 (1.3) a
`0 (0.0)
`2 (1.3) a
`0 (0.0)
`
`6 (4.0)
`7 (4.7)
`1 (0.7) a
`1 (0.7) a
`0 (0.0)
`
`7 (4.7)
`1 (0.7) a
`0 (0.0)
`
`2 (1.3) a
`2 (1.3) a
`0 (0.0) a
`
`Body System
`Adverse Reaction
`Fatigue and asthenia
`Pyrexia b
`Edema peripheral
`Pain
`Infections and infestations
`Upper respiratory tract
`infection b
`Pneumonia b
`Neutropenic sepsis b
`Gastrointestinal disorders
`Diarrhea
`Constipation
`Nausea
`Vomiting
`Musculoskeletal and
`connective tissue disorders
`Back pain b
`Bone pain b
`Muscle spasms
`Arthralgia
`Pain in extremity
`Respiratory, thoracic and
`mediastinal disorders
`Dyspnea b
`Cough
`Chronic obstructive
`pulmonary disease b
`Nervous system disorders
`Peripheral neuropathy
`Dizziness
`Headache
`
`ALVOGEN, Exh. 1027, p. 0012
`
`

`

`All Adverse Reactions
`(≥5% in POMALYST + Low-dose
`Dex arm, and at least 2% points
`higher than the High-dose-Dex arm)
`
`POMALYST +
`Low-dose Dex
`(N=300)
`17 (5.7)
`5 (1.7) a
`
`High-dose Dex
`(N=150)
`2 (1.3)
`0 (0.0) a
`
`Grade 3 or 4
`(≥1% in POMALYST + Low-dose
`Dex arm, and at least 1% point higher
`than the High-dose-Dex arm)
`POMALYST +
`Low-dose Dex
`(N=300)
`2 (0.7) a
`3 (1.0)
`
`High-dose Dex
`(N=150)
`0 (0.0) a
`0 (0.0)
`
`38 (12.7)
`28 (9.3) a
`12 (4.0) a
`
`23 (7.7)
`22 (7.3)
`15 (5.0)
`
`15 (5.0)
`10 (3.3) a
`8 (2.7) a
`
`7 (2.3) a
`
`4 (1.3) a
`
`3 (1.0) a
`
`12 (8.0)
`12 (8.0) a
` 9 (6.0) a
`
`2 (1.3)
`5 (3.3)
`1 (0.7)
`
`1 (0.7)
`3 (2.0) a
`1 (0.7) a
`
`2 (1.3) a
`
`2 (1.3) a
`
`1 (0.7) a
`
`3 (1.0) a
`12 (4.0)
`5 (1.7)
`
`3 (1.0)
`0 (0.0) a
`0 (0.0) a
`
`14 (4.7)
`8 (2.7)
`8 (2.7)
`
`5 (1.7)
`
`3 (1.0)
`
`3 (1.0)
`
`2 (1.3) a
`4 (2.7)
`1 (0.7)
`
`0 (0.0)
`0 (0.0) a
`0 (0.0) a
`
`1 (0.7)
`2 (1.3)
`0 (0.0)
`
`0 (0.0)
`
`0 (0.0)
`
`0 (0.0)
`
`31 (10.3) a
`
`18 (12.0) a
`
`19 (6.3)
`
`8 (5.3)
`
`5 (1.7) a
`
`1 (0.7) a
`
`5 (1.7)
`
`1 (0.7)
`
`6 (2.0) a
`
`3 (2.0) a
`
`4 (1.3)
`
`0 (0.0)
`
`Body System
`Adverse Reaction
`Tremor
`Depressed level of
`consciousness
`Metabolism and nutrition
`disorders
`Decreased appetite
`Hypokalemia
`Hypocalcemia
`Skin and subcutaneous tissue
`disorders
`Rash
`Pruritus
`Hyperhidrosis
`Investigations
`Neutrophil count decreased
`Platelet count decreased
`White blood cell count
`decreased
`Alanine aminotransferase
`increased
`Aspartate aminotransferase
`increased
`Lymphocyte count
`decreased
`Renal and urinary disorders
`Renal failure
`Injury, poisoning and
`procedural complications
`Femur fracture b
`Reproductive system and
`breast disorders
`Pelvic pain
`
`ALVOGEN, Exh. 1027, p. 0013
`
`

`

`a Percentage did not meet the criteria to be considered as an adverse reaction for POMALYST for that category of event (i.e., all adverse events or Grade 3
`or 4 adverse events).
`b Serious adverse reactions were reported in at least 3 patients in the POM + Low-dose Dex arm, AND at least 1% higher than the High-dose-Dex arm
`percentage.
`Data cutoff: 01 March 2013
`
`Other Adverse Reactions
`Other adverse reactions of POMALYST in patients with multiple myeloma, not described above, and
`considered important:
`
`Cardiac disorders: Myocardial infarction, Atrial fibrillation, Angina pectoris, Cardiac failure congestive
`Ear and labyrinth disorders: Vertigo
`Gastrointestinal disorders: Abdominal pain
`General disorders and administration site conditions: General physical health deterioration, Non-cardiac
`chest pain, Multi-organ failure
`Hepatobiliary disorders: Hyperbilirubinemia
`Infections and infestations: Pneumocystis jiroveci pneumonia, Respiratory syncytial virus infection,
`Neutropenic sepsis, Bacteremia, Pneumonia respiratory syncytial viral, Cellulitis, Urosepsis, Septic shock,
`Clostridium difficile colitis, Pneumonia streptococcal, Lo