Elrexfio

Description for Elrexfio

Elranatamab-bcmm is a bispecific B-cell maturation antigen (BCMA)directed CD3 T-cell engager. It is a bispecific, humanized immunoglobulin 2alanine (IgG2Δa) kappa antibody derived from two monoclonal antibodies (mAbs), an antiBCMA mAb and an antiCD3 mAb. Each of these mAbs contributes one distinct heavy (H) chain and one distinct light (L) chain to the bispecific elranatamab-bcmm. The resulting 4chain bispecific antibody is covalently linked via five inter-chain disulfide bonds. Elranatamab-bcmm is produced using two recombinant Chinese hamster ovary (CHO) cell lines, one that contains the DNA encoding the sequence for anti-BCMA monoclonal antibody (mAb) and one that contains the sequence for antiCD3 mAb, which are grown separately in suspension culture using chemically defined (CD), animal-derived component-free (ACF) media. The molecular weight of Elranatamab-bcmm is approximately 148.5 kDa.

ELREXFIO™ (elranatamab-bcmm) injection is a sterile, preservativefree, clear to slightly opalescent, and colorless to pale brown liquid solution for subcutaneous administration. ELREXFIO (Elranatamab-bcmm) is supplied at a concentration of 40 mg/mL in either 76 mg/1.9 mL or 44 mg/1.1 mL singledose vials. Each mL of solution contains 40 mg elranatamab-bcmm, edetate disodium (0.045 mg), histidine (1.12 mg), L-histidine hydrochloride monohydrate (2.67 mg), polysorbate 80 (0.2 mg), sucrose (85 mg) and Water for Injection. The pH is 5.8.

ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere in labeling:

• Cytokine Release Syndrome [see Warnings and Precautions (5.1)].
• Neurologic Toxicity, Including ICANS [see Warnings and Precautions (5.2)].
• Infections [see Warnings and Precautions (5.4)].
• Neutropenia [see Warnings and Precautions (5.5)].
• Hepatotoxicity [see Warnings and Precautions (5.6)].

Clinical Trials Experience

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.

Relapsed/Refractory Multiple Myeloma

MagnetisMM-3

The safety of ELREXFIO was evaluated in MagnetisMM-3 [see Clinical Studies (14)]. The safety population described (n = 183) includes patients who received the recommended dosage regimen of 12 mg subcutaneously on Day 1, 32 mg on Day 4, and 76 mg once weekly starting on Day 8. Among patients who received ELREXFIO, 42% were exposed for 6 months or longer and 9% were exposed for one year or longer.

The median age of patients who received ELREXFIO was 68 years (range: 36 to 88 years); 48% were female; 61% were White, 10% were Hispanic/Latino, 9% were Asian, and 6% were Black or African American.

Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule. Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis (13%), CRS (13%), upper respiratory tract infection (4.4%), acute kidney injury (3.8%), urinary tract infection (3.3%), COVID-19 (3.3%), encephalopathy (3.3%), pyrexia (2.2%), and febrile neutropenia (2.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.3%), sepsis (2.7%), acute respiratory distress syndrome (0.5%), cardio-respiratory arrest (0.5%), cardiogenic shock (0.5%), cardiopulmonary failure (0.5%), COVID-19 (0.5%), failure to thrive (0.5%), and pulmonary embolism (0.5%).

Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%).

Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia.

The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

Table 8 summarizes adverse reactions in MagnetisMM-3.

Table 8. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3

System Organ Class Preferred Term	ELREXFIO N= 183
	All Grades (%)	Grade 3 or 4 (%)
Immune system disorders
Cytokine release syndrome	58	0.5#
Hypogammaglobulinemia*	13	2.2#
General disorders and site administration conditions
Fatigue*	43	6#
Injection site reaction*	37	0
Pyrexia	21	2.7#
Edema*	18	1.1#
Gastrointestinal disorders
Diarrhea	36	1.1#
Nausea	21	0
Constipation	14	0
Vomiting	14	0
Infections
Upper respiratory tract infection*	36	4.9
Pneumoniaa	32	19
Sepsisb	15	11
Urinary tract infection*	12	4.4#
Musculoskeletal and connective tissue disorders
Musculoskeletal pain*	34	2.7#
Metabolism and nutrition disorders
Decreased appetite	26	1.1#
Skin and Subcutaneous Tissue disorders
Rashc	26	0
Dry skin	14	0
Skin exfoliation*	10	0
Respiratory, thoracic and mediastinal disorders
Cough*	24	0
Dyspnea*	15	3.3#
Nervous system disorders
Headache	18	0
Encephalopathyd	14	2.2
Sensory neuropathye	13	0.5#
Motor dysfunctionf	14	1.1#
Cardiac disorders
Cardiac arrhythmia*	16	1.6
Vascular disorders
Hemorrhage*	13	1.6
Psychiatric disorders
Insomnia	13	0
Injury, poisoning and procedural complications
Fall	10	0.5#
Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria. *      Includes other related terms. #      Only grade 3 adverse reactions occurred. Pneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. Sepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. Encephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor.

Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barré syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis and cytomegalovirus infection.

Table 9 summarizes laboratory abnormalities in MagnetisMM-3.

Table 9. Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3^a

Laboratory Abnormality	ELREXFIOb
	All Grades (%)	Grade 3 or 4 (%)
Hematology
Lymphocyte count decreased	91	84
White blood cell decreased	69	40
Hemoglobin decreased	68	43
Neutrophil count decreased	62	51
Platelet count decreased	61	32
Chemistry
Albumin decreased	55	6
AST increase	40	6
Creatinine increased	38	3.3
Potassium decreased	36	8
ALT increase	36	3.8
Alkaline phosphatase increased	34	1.1
Creatinine clearance decreased	32	10
Laboratory tests were graded according to NCI-CTCAE Version 0. The denominator used to calculate the rate varied from 181 to 183 based on the number of patients with a baseline value and at least one post-treatment value.

Drug Interactions for Elrexfio

For certain CYP substrates, minimal changes in the concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with ELREXFIO.

ELREXFIO causes release of cytokines [see Clinical Pharmacology (12.2)] that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur after the first dose of ELREXFIO Day 1 and up to 14 days after the 32 mg dose on Day 4 and during and after CRS [see Warnings and Precautions (5.1)].

Warnings for Elrexfio

Included as part of the PRECAUTIONS section.

Precautions for Elrexfio

Cytokine Release Syndrome (CRS)

ELREXFIO can cause CRS, including life-threatening or fatal reactions [see Adverse Reactions (6.1)].

In the clinical trial, CRS occurred in 58% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2)], with Grade 1 CRS in 44% of patients, Grade 2 CRS in 14% of patients, and Grade 3 CRS in 0.5% of patients. Recurrent CRS occurred in 13% of patients. Most patients experienced CRS after the first step-up dose (43%) or the second step-up dose (19%), with 7% of patients having CRS after the first treatment dose and 1.6% of patients after a subsequent dose. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose, with a median duration of 2 (range: 1 to 19) days.

Clinical signs and symptoms of CRS may include, but are not limited to, fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes.

Initiate therapy according to the ELREXFIO step-up dosing schedule to reduce risk of CRS and monitor patients following administration of ELREXFIO accordingly [see Dosage and Administration (2.2, 2.5)]. Administer pre-treatment medications prior to each dose in the step-up dosing schedule to reduce risk of CRS [see Dosage and Administration (2.3)].

Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, evaluate patients immediately for hospitalization. Manage CRS according to the recommendations and consider further management per current practice guidelines. Withhold or permanently discontinue ELREXFIO based on severity [see Dosage and Administration (2.5)].

ELREXFIO is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)].

Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

ELREXFIO can cause serious or life-threatening neurologic toxicity, including ICANS [see Adverse Reactions (6.1)].

In the clinical trial, neurologic toxicity occurred in 59% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2)], with Grade 3 or 4 neurologic toxicity occurring in 7% of patients.

Neurologic toxicities included headache (18%), encephalopathy (15%), motor dysfunction (13%), sensory neuropathy (13%), and Guillain-Barré Syndrome (0.5%).

In the clinical trial, ICANS occurred in 3.3% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2)]. Most patients had ICANS after the first step-up dose (2.7%), 1 (0.5%) patient had ICANS after the second step-up dose and 1 (0.5%) patient had ICANS after subsequent dose(s). Recurrent ICANS occurred in 1.1% of patients. The median time to onset was 3 (range: 1 to 4) days after the most recent dose, with a median duration of 2 (range: 1 to 18) days. The most frequent clinical manifestations of ICANS included a depressed level of consciousness and Grade 1 or Grade 2 Immune Effector Cell-Associated Encephalopathy (ICE) scores. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity occur. Monitor patients for signs and symptoms of neurologic toxicities during treatment with ELREXFIO. At the first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on severity. Withhold or permanently discontinue ELREXFIO based on severity per recommendations [see Dosage and Administration (2.5)] and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity including ICANS, patients receiving ELREXFIO are at risk of depressed level of consciousness. Advise patients not to drive or operate heavy or potentially dangerous machinery for 48 hours after completing each of the 2 step-up doses and the first treatment dose within the ELREXFIO step-up dosing schedule and in the event of new onset of any neurological toxicity symptoms until symptoms resolve [see Dosage and Administration (2.2)].

ELREXFIO is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)].

ELREXFIO REMS

ELREXFIO is available only through a restricted program under a REMS called the ELREXFIO REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].

Notable requirements of the ELREXFIO REMS include the following:

• Prescribers must be certified with the program by enrolling and completing
• Prescribers must counsel patients receiving ELREXFIO about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with ELREXFIO Patient Wallet Card.
• Pharmacies and healthcare settings that dispense ELREXFIO must be certified with the ELREXFIO REMS program and must verify prescribers are certified through the ELREXFIO REMS program.
• Wholesalers and distributers must only distribute ELREXFIO to certified pharmacies or healthcare

Further information about the ELREXFIO REMS program is available at www.ELREXFIOREMS.com or by telephone at 1-844-923-7845.

Infections

ELREXFIO can cause severe, life-threatening, or fatal infections. In the clinical trial, in patients who received ELREXFIO according to the recommended dosing schedule, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade 3 or 4 infections in 31%, and fatal infections in 7%. The most common serious infections reported (≥5%) were pneumonia and sepsis [see Adverse Reactions (6.1)].

Do not initiate treatment with ELREXFIO in patients with active infections. Monitor patients for signs and symptoms of infection prior to and during treatment with ELREXFIO and treat appropriately. Withhold or permanently discontinue ELREXFIO based on severity [see Dosage and Administration (2.5)]. Administer prophylactic antimicrobial and anti-viral medications according to current practice guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIG) as appropriate.

Neutropenia

ELREXFIO can cause neutropenia and febrile neutropenia. In patients who received ELREXFIO at the recommended dose in the clinical trial, decreased neutrophils occurred in 62% of patients, with Grade 3 or 4 decreased neutrophils in 51%. Febrile neutropenia occurred in 2.2% of patients [see Adverse Reactions (6.1)].

Monitor complete blood cell counts at baseline and periodically during treatment. Provide supportive care according to current practice guidelines. Monitor patients with neutropenia for signs of infection. Withhold ELREXFIO based on severity [see Dosage and Administration (2.5)].

Hepatotoxicity

ELREXFIO can cause hepatotoxicity. In the clinical trial, elevated ALT occurred in 36% of patients, with Grade 3 or 4 ALT elevation occurring in 3.8%; elevated AST occurred in 40% of patients, with Grade 3 or 4 AST elevation occurring in 6%. Grade 3 or 4 total bilirubin elevations occurred in 0.5% of patients [see Adverse Reactions (6.1)]. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold ELREXFIO or consider permanent discontinuation of ELREXFIO based on severity [see Dosage and Administration (2.5)].

Embryo-Fetal Toxicity

Based on its mechanism of action, ELREXFIO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ELREXFIO and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity or genotoxicity studies have been conducted with elranatamab-bcmm.

No animal studies have been performed to evaluate the effects of elranatamab-bcmm on fertility.

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Cytokine Release Syndrome (CRS)

Discuss the signs and symptoms associated with CRS, including fever, hypoxia, chills, hypotension, tachycardia, and elevated liver enzymes. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of CRS. Advise patients that they will be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose [see Dosage and Administration (2.5), Warnings and Precautions (5.1)].

Neurologic Toxicity, Including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)

Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, including headache,

encephalopathy, motor dysfunction, sensory neuropathy, and Guillain-Barré Syndrome. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery for 48 hours after completing each of the 2 step-up doses and the first treatment dose within the ELREXFIO step-up dosing schedule and in the event of new onset of any neurological toxicity symptoms until symptoms resolve [see Dosage and Administration (2.5), Warnings and Precautions (5.2)].

ELREXFIO REMS

ELREXFIO is available only through a restricted program called ELREXFIO REMS. Inform patients that they will be given an ELREXFIO Patient Wallet Card that they should carry with them at all times and show to all of their healthcare providers. This card describes signs and symptoms of CRS and neurologic toxicity, including ICANS which, if experienced, should prompt the patient to immediately seek medical attention [see Warnings and Precautions (5.3)].

Infections

Discuss the signs and symptoms of infection [see Dosage and Administration (2.5), Warnings and Precautions (5.4)].

Neutropenia

Discuss the signs and symptoms associated with neutropenia and febrile neutropenia [see Dosage and Administration (2.5), Warnings and Precautions (5.5)].

Hepatotoxicity

Advise patients that liver enzyme elevations may occur and that they should report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.6)].

Embryo-Fetal Toxicity

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use effective contraception during treatment with ELREXFIO and for 4 months after the last dose [see Warnings and Precautions (5.7), Use in Specific Populations (8.1, 8.3)].

Lactation

Advise women not to breastfeed during treatment with ELREXFIO and for 4 months after the last dose [see Use in Specific Populations (8.2)].

OVERDOSAGE

No information provided

Contraindications for Elrexfio

No information provided

Clinical Pharmacology for Elrexfio

Mechanism of Action

Elranatamab-bcmm is a bispecific B-cell maturation antigen (BCMA)-directed T-cell engaging antibody that binds BCMA on plasma cells, plasmablasts, and multiple myeloma cells and CD3 on T-cells leading to cytolysis of the BCMA-expressing cells. Elranatamab-bcmm activated T-cells, caused proinflammatory cytokine release, and resulted in multiple myeloma cell lysis.

Pharmacodynamics

Cytokine Concentrations

Transient elevation of circulating cytokines IL-2, IL-6, IL-8, IL-10, TNF-α, and IFN-γ was observed at dosage levels of 30 µg/kg (0.03 times the approved recommended dosage) and above. After administration of the approved recommended dosage of ELREXFIO, the highest elevation of cytokines was generally observed within 72 hours after first elranatamab-bcmm dose at 12 mg on Day 1, and generally returned to baseline prior to the administration of the first full dose 76 mg on Day 8.

Pharmacokinetics

Pharmacokinetic parameters are presented as geometric mean (coefficient of variation [CV]%) and are based upon subcutaneously administered unless otherwise specified.

Elranatamab-bcmm exhibits dose proportional pharmacokinetics over dose range from 6 to 76 mg (0.079 to 1 times the approved recommended dosage). Elranatamab-bcmm maximum concentration [33.0 mcg/mL (46%)] is achieved at the end of weekly dosing regimen (i.e., at week 24 of 76 mg weekly dosing). Pharmacokinetic exposures are summarized for the recommended dosage of ELREXFIO in Table 10.

Table 10. Pharmacokinetic Parameters of Elranatamab-bcmm in Subjects with Relapsed or Refractory Multiple Myeloma

Timepoint	Parameters
	Cavg (mcg/mL)	Cmax (mcg/mL)	Ctrough (mcg/mL)
First full 76 mg dose	3.1 (94%)	3.8 (94%)	3.3 (102%)
End of weekly dose (week 24)a	32.0 (46%)	33.0 (46%)	30.5 (48%)
Steady state (biweekly dosing)a,b	17.7 (53%)	19.5 (51%)	15.1 (60%)
Steady state (every 4 weeks dosing)a,c	8.8 (58%)	11.5 (54%)	5.9 (78%)
In patients who have achieved a Steady state exposure of elranatamab biweekly dose is approximated at week Steady state exposure of elranatamab once every 4 weeks dose is approximated at week

Absorption

The mean bioavailability of elranatamab-bcmm was 56.2% when administered subcutaneously. The median (min, max) Tmax after elranatamab SC administration was 7 (3 to 7) days.

Distribution

The steady state volume of distribution of elranatamab-bcmm was 7.76 L (33%).

Elimination

The half-life of elranatamab-bcmm is 22 (64%) days at the 76 mg dosage, with clearance of 0.324 L/day (100%) following 24 weeks dosing.

Metabolism

Elranatamab-bcmm is expected to be metabolized into small peptides by catabolic pathways.

Specific Populations

No clinically significant differences in the pharmacokinetics of elranatamab-bcmm were observed based on age (36 to 89 years), sex, race (White, Asian, or Black), body weight (37 to 160 kg), mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] by Modification of Diet in Renal Disease [MDRD] method: 30 to 89 mL/min), or mild hepatic impairment (total bilirubin 1 to ≤1.5 x ULN or any AST greater than ULN).

The effects of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR <15 mL/min), or moderate to severe hepatic impairment (total bilirubin >1.5 times ULN and any AST) on the PK of elranatamab-bcmm are unknown.

Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of elranatamab-bcmm or of other elranatamab products.

In the MagnetisMM-3 study, of the 168 participant who received recommended step-up and full dosage of ELREXFIO for up to 36 months and are evaluable for presence of ADA against elranatamab-bcmm, 9.5% (16/168) of patients tested positive for anti-elranatamab-bcmm-antibodies. Among the 16 patients who tested positive for ADAs, 56% (9/16) tested positive for neutralizing antibodies against elranatamab-bcmm. The effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of ELREXFIO products is unknown.

MEDICATION GUIDE
ELREXFIO^TM (el-reks-fe-o)
(elranatamab-bcmm)
injection, for subcutaneous use

What is the most important information I should know about ELREXFIO?

ELREXFIO may cause serious side effects, including:

• Cytokine Release Syndrome (CRS). CRS is common during treatment with ELREXFIO and can also be serious, life-threatening, or can lead to death. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS, including:

  fever of 100.4 °F (38 °C) or higher trouble breathing chills dizziness or light-headedness fast heartbeat

  headache increased liver enzymes in your blood. See “What are the possible side effects of ELREXFIO?” for more information about the signs and symptoms of liver problems.

  Due to the risk of CRS, you will receive ELREXFIO on a “step-up dosing schedule” and should be hospitalized for 48 hours after the first “step-up” dose and for 24 hours after the second “step-up” dose of ELREXFIO.

  • During the step-up dosing schedule:
    • for your first dose, you will receive a smaller “step-up” dose of ELREXFIO on Day 1 of your treatment
    • for your second dose, you will receive a larger “step-up” dose of ELREXFIO, which is usually given on Day 4 of your treatment
    • for your third dose, you will receive the first full “treatment” dose of ELREXFIO, which is usually given on Day 8 of your treatment
  • If your dose of ELREXFIO is delayed for any reason, you may need to repeat the step-up dosing schedule.
  • Before each step-up dose and the first full treatment dose of ELREXFIO, you will receive medicines to help reduce your risk of Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.
  • See “How will I receive ELREXFIO?” for more information about how you will receive ELREXFIO.

• Neurologic ELREXFIO can cause neurologic problems that can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of neurologic problems, including:

  headache agitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations) trouble speaking, thinking, remembering things, paying attention, or understanding things

  problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms numbness and tingling (feeling like “pins and needles”) burning, throbbing, or stabbing pain changes in your handwriting

• ELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare The ELREXFIO Patient Wallet Card lists symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the symptoms listed on the ELREXFIO Patient Wallet Card. You may need to be treated in a hospital.

Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with ELREXFIO, as well as other side effects, and will treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with ELREXFIO if you develop CRS, neurologic problems, or any other side effects that are severe.

If you have any questions about ELREXFIO, ask your healthcare provider.

See “What are possible side effects of ELREXFIO?” for more information about side effects.

What is ELREXFIO?

ELREXFIO is a prescription medicine used to treat adults with multiple myeloma who:

• have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and
• their cancer has come back or did not respond to prior treatment.

It is not known if ELREXFIO is safe and effective in children.

Before receiving ELREXFIO, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection.
• are pregnant or plan to become ELREXFIO may harm your unborn baby.

  Females who are able to become pregnant:

  • Your healthcare provider should do a pregnancy test before you start treatment with ELREXFIO.
  • You should use effective birth control (contraception) during treatment and for 4 months after your last dose of ELREXFIO.
  • Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO.
• are breastfeeding or plan to It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of ELREXFIO.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive ELREXFIO?

• ELREXFIO will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in your stomach-area (abdomen). Your thigh or another area of your body may also be used.
• See “What is the most important information I should know about ELREXFIO?” for more information about how you will receive ELREXFIO.
• After you receive your first full “treatment” dose, ELREXFIO is usually given 1 time each week through Week 24.
• Starting on Week 25, your future doses will usually be given 1 time every 2 weeks.
• Starting on Week 49, your future doses will usually be given 1 time every 4 weeks.
• Your healthcare provider will decide the time between doses and how long you will receive treatment with ELREXFIO.

If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. It is important for you to be monitored closely for side effects during treatment with ELREXFIO.

What should I avoid while receiving ELREXFIO?

Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities during treatment with ELREXFIO:

• for 48 hours after completing each of the 2 doses of ELREXFIO that are part of the “step-up dosing schedule” and your first full treatment dose, and
• at any time during treatment with ELREXFIO if you develop any new neurologic symptoms such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away.

See “What is the most important information I should know about ELREXFIO?” for more information about signs and symptoms of neurologic problems.

What are the possible side effects of ELREXFIO? ELREXFIO may cause serious side effects, including:

• See “What is the most important information I should know about ELREXFIO?”
• Upper respiratory tract infections and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death.
  • Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO.
  • Tell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including:

    fever of 100.4 °F (38 °C) or higher chills cough shortness of breath

    chest pain sore throat pain during urination feeling weak or generally unwell

• Decreased white blood cell counts. Decreased white blood cell counts are common during treatment with ELREXFIO and can also be Fever can happen with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will treat you as needed.

• Liver problems. ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:

  tiredness loss of appetite pain in your right upper stomach-area (abdomen)

  dark urine yellowing of your skin or the white part of your eyes

Your healthcare provider will check your blood and monitor you for signs and symptoms of these serious side effects before you start and during treatment with ELREXFIO and may temporarily or completely stop treatment with ELREXFIO if you develop certain side effects.

The most common side effects of ELREXFIO include:

tiredness injection site reaction, such as redness, itching, pain, bruising, rash, swelling, tenderness diarrhea muscle and bone pain

decreased appetite rash cough nausea fever

The most common severe abnormal blood test results with ELREXFIO include decreased white blood cells, red blood cells, and platelets.

These are not all of the possible side effects of ELREXFIO.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of ELREXFIO.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for more information about ELREXFIO that is written for health professionals.

What are the ingredients in ELREXFIO?

Active ingredient: elranatamab-bcmm

Inactive ingredients: edetate disodium, histidine, L-histidine hydrochloride monohydrate, polysorbate 80, sucrose, and Water for Injection

Manufactured by: Pfizer Inc., NY, NY 10001
US License No. 2001

LAB-1551-1.3

For more information on ELREXFIO, go to www.ELREXFIO.com

For more information on Pfizer, go to www.Pfizer.com or call 1-800-438-1985

This Medication Guide has been approved by the U.S. Food and Drug Administration.