Indications

    BKEMV™ (eculizumab-aeeb) is indicated for the treatment of:

  • patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
  • patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
  • generalized myasthenia gravis (g...  Read moreMG) in adult patients who are anti- acetylcholine receptor (AchR) antibody positive.

    • BKEMV is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

    BKEMVTM (eculizumab-aeeb) is indicated for the treatment of:

  • patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
  • patients with atypical... Read more hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
  • generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive.

    • BKEMV is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

Indications Dosing Storage and Handling Prescribing Information Enroll in BKEMV™ REMS

BEHIND BKEMVTM

A ROBUST BIOSIMILARS PROGRAM

Totality of Evidence / Biosimilarity & Extrapolation

BKEMV™ MEETS THE FDA REQUIREMENTS FOR BIOSIMILARITY1-3

BKEMV™ is highly similar to Soliris® based on a totality of evidence, with no clinically meaningful differences in safety or efficacy.2

*BKEMV™ was studied in patients with PNH, a population considered sensitive due to robust treatment effect of the reference product in clinical trials, with relevant endpoints demonstrating efficacy and safety across indications. Sensitive patient populations help detect clinically meaningful differences between a biosimilar and reference drug.5,6

†Complement pathways including classical (CP), alternative (AP), and lectin (LP) pathways8

BKEMV™ IS APPROVED FOR PNH, aHUS AND gMG BASED ON THE TOTALITY OF EVIDENCE

BKEMV™ TOTALITY OF EVIDENCE3,7,‡
EXTRAPOLATION3, 9-11
APPROVED INDICATIONS FOR BKEMVTM 1

Comparative Clinical Study (Phase 3)

Paroxysmal nocturnal hemoglobinuria (PNH) (n=42)

Comparative Clinical Pharmacology (Phase 1)

Pharmacokinetics (PK) and
Pharmacodynamics (PD) (n = 219)

Analytical and Non-clinical studies

Multiple in vitro and in vivo analytical similarity studies including toxicology

Scientific justification for similarity

  • Mechanism of action
  • PK / PD
  • Immunogenicity
  • Safety

EXTRAPOLATION3, 9-11

The FDA extrapolates these data to consider approval of the biosimilar for all the indications of the reference drug.

APPROVED INDICATIONS
FOR BKEMVTM1

  • Paroxysmal nocturnal hemoglobinuria (PNH)
  • Atypical hemolytic uremic syndrome (aHUS)
  • Generalized myasthenia gravis (gMG)

PD = pharmacodynamic;
PK = pharmacokinetic.

‡Totality of evidence establishes structural and functional equivalence, and includes nonclinical evaluation, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and comparative clinical study data.

WHAT IS EXTRAPOLATION?

According to the FDA, extrapolation of data is used to support the approval of a proposed biosimilar product in one or more additional indications for which the reference product is approved, but for which the biosimilar has not been studied in clinical trials.11

Totality of Evidence / Study Design

BKEMV™ is the only approved eculizumab biosimilar with clinical data in Soliris-stable patients

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Primary endpoints:

  • LDH level at week 271
  • Time-adjusted AUEC of LDH from week 13 to 27, week 39 to 53, and week 65 to 79.

Key Secondary Endpoint:* Mean total complement (50% total hemolytic complement activity [CH50]) at baseline and various time points throughout the study1

AUEC = area under the effect curve;
AUC = area under curve;
LDH= lactate dehydrogenase;
PK = pharmacokinetics;
RBC = red blood cell;
Q2W= once every two weeks.

*Additional secondary endpoints: Total hemoglobin, Serum-free hemoglobin, Haptoglobin, Bilirubin, Degree of hemoglobinuria, Type III erythrocytes, Granulocytes, LDH at Week 53 and 79, LDH-time profile, Incidence of RBC transfusion, PK AUC of BKEMV and Soliris.1

SOLIRIS®-STABLE PATIENTS WERE ENROLLED TO REPLICATE A TREATMENT SCENARIO THAT MAY REFLECT REAL WORLD CLINICAL PRACTICE1,2

Totality of Evidence / Efficacy

BKEMV DEMONSTRATED HIGHLY SIMILAR EFFICACY TO SOLIRIS BY MEETING THE PRIMARY ENDPOINT1

efficacy
efficacy-1-mob
efficacy-2
efficacy-2-mob
efficacy-table
efficacy-table-mob

Totality of Evidence / Safety / Immunogenicity

SAFETY AND IMMUNOGENICITY WERE PROVEN CONSISTENT WITH SOLIRIS® in 79-week study with Soliris®-stable patients

INCIDENCE OF ADVERSE EVENTS (≥ 10% IN ANY TREATMENT GROUP) DURING PRIMARY ASSESSMENT (UP TO MONTH 12)1

AE category, n (%)* BKEMV™ (N = 41)‡ Soliris® (N = 42)
Any AE 33 (80.5) 39 (92.9)
Any Grade ≥3 AE 8 (19.5) 12 (28.6)
Any fatal AE 0 0
Any SAE† 7 (17.1) 2 (4.8)
Any AE leading to discontinuation of IP/study 0 1 (2.4)‡
Any event of interest 17 (41.5) 15 (35.7)
Infusion reaction AE§ 15 (36.6) 15 (35.7)
Serious infection AE** 3 (7.3) 0

AE = adverse event; AMQ = Amgen MedDRA query; IP = investigational product; SAE = serious adverse event; SMQ = standardized MedDRA Query; SOC = system organ class; TEAE = treatment emergent adverse events

*Only TEAEs were summarized. For each category, patients were included only once, even if they experienced multiple events in that category.

†One SAE was IP related; all others were single events with alternative etiology.

‡One subject in the SOLIRIS. treatment group discontinued IP/study due to AEs of Grade 2 non-serious asthenia and Grade 2 non-serious fatigue. The subject discontinued the study prior to treatment crossover, as reflected in BKEMV group n=41.

§Identified using the hypersensitivity SMQ (broad) and infusion reaction AMQ (broad) search strategies.

**Identified using the infections and infestations SOC (broad) search strategy.

NO PATIENTS IN EITHER TREATMENT ARM DEVELOPED NEUTRALIZING ANTIBODIES.2

Totality of Evidence / Clinical PK / Nonclinical

OVERLAPPING DATA CURVES DEMONSTRATE BKEMVTM BIOEQUIVALENCE TO SOLIRIS®

Serum concentrations of BKEMVTM and Soliris® were highly similar at all timepoints measured (in healthy volunteers)1

Study design: Healthy adult male subjects (N = 219) received BKEMV® or eculizumab (US and EU formulations) randomized (1:1:1) to receive a single IV dose of 300 mg. PK, PD, and safety were evaluated over 24 hours, then follow-up evaluations of PK, PD, and safety were conducted over time (days 3, 5, 8, 11, 15, 22, 29, 36, 43, 50, 57).

IV = intravenous; PD = pharmacodynamic; PK = pharmacokinetic.

Similar pharmacodynamics were demonstrated by area between the effect curve of ch50-time data (in healthy volunteers)1

Study design: Healthy adult male subjects (N = 219) received BKEMV™ or eculizumab (US and EU formulations) randomized (1:1:1) to receive a single IV dose of 300 mg. PK, PD, and safety were evaluated over 24 hours, then follow-up evaluations were conducted over time (days 3, 5, 8, 11, 15, 22, 29, 36, 43, 50, 57).

CH50 = 50% hemolytic complement; IV = intravenous; PD = pharmacodynamic; PK = pharmacokinetic.

Important Safety Information

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Eculizumab products, complement inhibitors, increase the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

  • Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of BKEMV, unless the risks of delaying therapy with BKEMV outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor. See Warnings and Precautions for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria.
  • Patients receiving eculizumab products are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected.

Because of the risk of serious meningococcal infections, BKEMV is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called BKEMV REMS.

Contraindications:BKEMV is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.

Other Infections

Use caution when administering BKEMV to patients with any other systemic infection. Serious infections with Neisseria species (other than Neisseria meningitidis), including disseminated gonococcal infections, have been reported.

Eculizumab products block terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections with Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with eculizumab products may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP recommendations. Patients receiving eculizumab products are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination.

Monitoring Disease Manifestations after BKEMV Discontinuation

Treatment Discontinuation for PNH:

Monitor patients after discontinuing BKEMV for at least 8 weeks to detect hemolysis.

Treatment Discontinuation for aHUS:

After discontinuing BKEMV, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis.

In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during BKEMV treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during BKEMV treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during BKEMV treatment.

If TMA complications occur after BKEMV discontinuation, consider reinstitution of BKEMV treatment, plasma therapy, or appropriate organ-specific supportive measures.

Thrombosis Prevention and Management

The effect of withdrawal of anticoagulant therapy during eculizumab products treatment has not been established. Therefore, treatment with eculizumab products should not alter anticoagulant management.

Infusion-Related Reactions

Administration of eculizumab products may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion-related reaction which required discontinuation of eculizumab. Interrupt BKEMV infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

The most frequently reported adverse reactions in:

  • the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea
  • the aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, and pyrexia
  • the gMG placebo-controlled clinical trial (≥10%) is musculoskeletal pain
Drug Interactions
  • Concomitant use of eculizumab products with plasma exchange (PE), plasmapheresis (PP) or fresh frozen plasma infusion (PE/PI) treatment can reduce serum eculizumab products concentrations and requires a supplement dose of BKEMV.
  • Concomitant use of eculizumab products with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of eculizumab products. Closely monitor for reduced effectiveness of BKEMV.

Please see full Prescribing Information for additional Important Safety Information.

INDICATIONS

BKEMV™ (eculizumab-aeeb) is indicated for the treatment:

  • patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
  • patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
  • generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive.

BKEMV is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

      *A stable patient was defined as a patient receiving eculizumab for ≥6 months and currently receiving 900 mg of eculizumab every 14 ± 2 days.2

      †BKEMV™ is not indicated for Neuromyelitis Optica Spectrum Disorder (NMOSD), for which Alexion has marketing exclusivity.1,3

References: 1. BKEMV (eculizumab-aeeb) Prescribing Information, Amgen. 2. Kulasekararaj A, et al. Am J Hematol. Published online August 22, 2024. 3. Soliris® (eculizumab) Prescribing Information, Alexion.

References: 1. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/media/82647/download. Accessed January 6, 2025. 2. US Food and Drug Administration. Overview of the regulatory guidance for the development and approval of biosimilar products in the US. www.fda.gov/media/90496/download. Accessed January 6, 2025. 3. Blauvelt A, Cohen AD, Puig L, Vender R, van der Walt J, Wu JJ. Biosimilars for psoriasis: preclinical analytical assessment to determine similarity. Br J Dermatol. 2016;174:282-286. 4. US Food and Drug Administration. Guidance for industry: pharmaceutical development. www.fda.gov/media/71535/download. Accessed January 6, 2025.

References: 1. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/media/82647/download. Accessed January 6, 2025. 2. US Food and Drug Administration. Guidance for industry: pharmaceutical development. www.fda.gov/media/71535/download. Accessed January 6, 2025. 3. US Food and Drug Administration. Generic drug facts. www.fda.gov/drugs/generic-drugs/generic-drug-facts. Accessed January 6, 2025. 4. Aspirin Prescribing Information, Bayer. 5. Taltz® (ixekizumab) Prescribing Information [revised 2021], Eli Lilly. 6. Amgen. A worldwide biologics leader. www.amgenbiosimilars.com/heritage/worldwide-biologics-leader. Accessed January 6, 2025. 7. Desanvicente-Celis Z, Gomez-Lopez A, Anaya JM. Similar biotherapeutic products: overview and reflections. Immunotherapy. 2012;4:1841-1857. 8. Amgen. Amgen Manufacturing. www.amgenbiosimilars.com/expertise/manufacturing. Accessed January 6, 2025.

References: 1. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/media/82647/download. Accessed January 6, 2025. 2. US Food and Drug Administration. Biosimilar product information. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information. Accessed January 6, 2025. 3. IQVIA. Biosimilars in the United States 2020-2024—competition, savings, and sustainability. October 2020.

Reference: 1. Risk Evaluation and Mitigation Strategy (REMS) Document. https://www.accessdata.fda.gov/drugsatfda_docs. Accessed Feb 24, 2025.
2. BKEMV™ (eculizumab-aeeb) Prescribing Information. Amgen, Inc.

References: 1. BKEMV™ (eculizumab-aeeb) Prescribing Information. Amgen, Inc. 2. US Food and Drug Administration, BKEMV FDA Approval Letter 2023. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information. Accessed January 17, 2025. 3. US Food and Drug Administration. Scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Accessed January 17, 2025. 4. US Food and Drug Administration. FDA webinar - overview of the regulatory framework and FDA's guidance for the development and approval of biosimilar and interchangeable products in the US. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm610901.htm. 5. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. April 2015. Accessed January 17, 2025. www.fda.gov/downloads/drugs/ guidances/ucm291128.pdf. 6. Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open. 2016;2:e000154. 7. Hutterer KM, Ip A, Kuhns S, Cao S, Wikström M, Liu J. Analytical Similarity Assessment of ABP 959 in Comparison with Eculizumab Reference Product. BioDrugs. 2021;35(5):563-577. 8. McBride HJ, Frazer-Abel A, Thiemann S, Lehto SG, Hutterer KM, Liu J. Functional similarity of ABP 959 and eculizumab in simulated serum models of aHUS and NMOSD. Ann Hematol. 2023;102(12):3299-3309. 9. Kenawy HI, Boral I, Bevington A. Complement-Coagulation Cross-Talk: A Potential Mediator of the Physiological Activation of Complement by Low pH. Front Immunol. 2015;6:215. 10. Chow V, Pan J, Chien D, Mytych DT, Hanes V. A randomized, double-blind, single-dose, three-arm, parallel group study to determine pharmacokinetic similarity of ABP 959 and eculizumab (Soliris®) in healthy male subjects. Eur J Haematol. 2020;105(1):66-74. 11. Kulasekararaj A, Lanza F, Arvanitakis A, et al. Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024;99(11):2108-2117.

References: 1. Kulasekararaj A, Lanza F, Arvanitakis A, et al. Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024,99(11):2108-2117. 2. Kulasekararaj A, Lanza F, Arvanitakis A, et al. Efficacy and safety of biosimilar candidate ABP959 as compared with eculizumab reference product in paroxysmal nocturnal hemoglobinuría.

Reference: 1. Kulasekararaj A, Lanza F, Arvanitakis A, et al. Efficacy and safety of biosimilar candidate ABP 959 as compared with eculizumab reference product in paroxysmal nocturnal hemoglobinuria.

References: 1. Kulasekararaj A, Lanza F, Arvanitakis A, et al. Efficacy and safety of biosimilar candidate ABP 959 as compared with eculizumab reference product in paroxysmal nocturnal hemoglobinuria. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 3893. 2. Kulasekararaj A, Lanza F, Arvanitakis A, et al. Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024;99(11):2108-2117.

Reference: 1. Chow V, Pan J, Chien D, Mytych DT, Hanes V. A randomized, double-blind, single-dose, three-arm, parallel group study to determine pharmacokinetic similarity of ABP 959 and eculizumab (Soliris®) in healthy male subjects. Eur J Haematol. 2020;105:66-74

References: 1. Amgen Biosimilars. Manufacturing. https://www.amgenbiosimilars.com/heritage/worldwide-biologics-leader. Accessed January 17, 2025. 2. Amgen Biosimilars. Amgen’s Heritage and Legacy. Available at: https://www.amgen.com.hk/science/biosimilars Accessed January 17, 2025.

References: 1. AVSOLA® (infliximab-axxq) Prescribing Information, Amgen Inc. 2. AMJEVITA™ (adalimumab-atto) Prescribing Information, Amgen Inc. 3. KANJINTI® (trastuzumab-anns) Prescribing Information, Amgen Inc. 4. MVASI® (bevacizumab-awwb) Prescribing Information, Amgen Inc. 5. RIABNI® (rituximab-arrx) Prescribing Information, Amgen Inc. 6. PAVBLUTM (aflibercept-ayyh) Prescribing Information, Amgen Inc. 7. BKEMV™ (eculizumabaeeb). Prescribing Information Amgen Inc. 8. Data on file, Amgen [Biosimilars Product Sales]; 2021. 9.Data on file, Amgen; [1]; 2024.

Reference: 1. Amgen. Amgen biosimilars. www.amgen.com/science/biosimilars.

Reference: 1. BKEMV™ (eculizumab-aeeb). Prescribing Information. Amgen Inc. 2. Kulasekararaj A, et al. Am J Hematol. Published online August 22, 2024

Reference: 1. BKEMV™ (eculizumab-aeeb). Prescribing Information. Amgen Inc.

References: 1. US Food and Drug Administration. FDA approves first interchangeable biosimilar for two rare diseases. https://www.fda.gov/news-events/ press-announcements/fda-approves-first-interchangeable-biosimilar-two-rare-diseases. 2. Amgen Biosimilars. Manufacturing. https://www.amgenbiosimilars.com/heritage/worldwide-biologics-leader. Accessed January 17, 2025. 3. Amgen Biosimilars. Amgen’s Heritage and Legacy Available at: https://www.amgen.com.hk/science/biosimilars Accessed January 17, 2025. 4. Amgen. Amgen History. Available at: https://www.amgen.com/about/%20amgen-history#:-:text=Over. Accessed January 17, 2025.

Important Safety Information

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
  • Eculizumab products, complement inhibitors, increase the risk of serious infections caused by Neisseria meningitidis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.