​​​​​​PFIZER IS BUILDING ONTO THE CLINICAL EXPERIENCE OF PEGFILGRASTIM

NYVEPRIA is an FDA-approved biosimilar to Neulasta® (pegfilgrastim)1*

Clinical Data in Support of Biosimilarity

Pharmacodynamic and pharmacokinetic profiles2

Study to assess PD/PK similarity in healthy volunteers

  • Treatment A: NYVEPRIA, 6-mg, single SC injection in the deltoid region
  • Treatment B: Neulasta-US, 6-mg, single SC injection in the deltoid region
  • Treatment C: Neulasta-EU, 6-mg, single SC injection in the deltoid region

Study description

  • A single-center, randomized, open-label, single-dose, comparator-controlled, 3-treatment, 3-period, 6-sequence crossover study that assessed the PD and PK of NYVEPRIA compared with Neulasta-US and Neulasta-EU following SC administration in healthy subjects

Primary PD endpoints

  • The primary PD endpoints were area under the effect vs time curve for ANC from the time of dose administration to 288 hours after dose administration (AUECANC) and the maximum observed value for ANC (ANC Cmax)
    • PD equivalence was assessed by constructing the 90% CIs for the GMR (test/reference) for AUECANC and ANC Cmax
  • The primary PK endpoints were the area under the serum pegfilgrastim vs time curve from the time of dose administration to time infinity (AUC0-inf) and Cmax
  • PK equivalence was assessed by constructing the 90% CIs for the GMR (test/reference) for AUC0-inf and Cmax. PK equivalence was concluded if the 90% CIs for both AUC0⁠-⁠inf and Cmax were completely contained within the acceptance limits of 80% to 125%
AUEC=area under the effect curve; ANC=absolute neutrophil count; CI=confidence interval; Cmax=maximum observed serum pegfilgrastim concentration; GMR=geometric mean ratio; PD=pharmacodynamics; PK=pharmacokinetics; SC=subcutaneous.


NYVEPRIA PD analysis established equivalence to Neulasta in support of biosimilarity2​​​​​​​

Mean ANC over time in healthy subjects

The 90% CIs for AUECANC and ANC Cmax were completely contained within the predefined equivalence limit of 80% to 125% for all study drug comparisons

   *Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar and the reference product.1

    †A total of 143 subjects, assigned to 1 of the 6 sequence groups, were included in the PK population and PD population; 10 subjects confirmed positive for antipegfilgrastim antibodies were excluded from PD and PK analyses.

Primary PK endpoint of mean serum concentration over time was similar across treatments among healthy subjects

​​​​​​​​​​​​​​The 90% CIs for AUC0-inf and Cmax were completely contained within the predefined equivalence limit of 80% to 125% for all study drug comparisons

Primary endpoints

The primary PK endpoints were the area under the serum pegfilgrastim vs time curve from the time of dose administration to time infinity (AUC0-inf), and the maximum observed serum pegfilgrastim concentration (Cmax). PK equivalence was assessed by constructing the 90% CIs for the GMR (test/reference) for AUC0-inf and Cmax. PK equivalence was concluded if the 90% CIs for both AUC0-inf and Cmax were completely contained within the acceptance limits of 80% to 125%.

Efficacy & Safety

  • Clinical Data in Support of Biosimilarity
  • Safety Data in Support of Biosimilarity

NYVEPRIA had a comparable safety profile vs Neulasta across adverse event categories2

Studies in support of biosimilarity in healthy volunteers

Review safety data
Contraindications
  • NYVEPRIA is contraindicated in patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products
  • Reactions have included anaphylaxis
Warnings and Precautions
Splenic Rupture
  • Splenic rupture, including fatal cases, can occur following the administration of pegfilgrastim products
  • Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving NYVEPRIA
Acute Respiratory Distress Syndrome (ARDS)
  • ARDS can occur in patients receiving pegfilgrastim products
  • Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving NYVEPRIA
  • Discontinue NYVEPRIA in patients with ARDS
Serious Allergic Reactions
  • Serious allergic reactions, including anaphylaxis, can occur in patients receiving pegfilgrastim products
  • The majority of reported events occurred upon initial exposure
  • Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti‐allergic treatment
  • Permanently discontinue NYVEPRIA in patients with serious allergic reactions
  • Do not administer NYVEPRIA to patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products
Use in Patients with Sickle Cell Disorders
  • Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving pegfilgrastim products
  • Discontinue NYVEPRIA if sickle cell crisis occurs
Glomerulonephritis
  • Glomerulonephritis has occurred in patients receiving pegfilgrastim products
  • The diagnoses were based on azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy
  • Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation of pegfilgrastim products
  • If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of NYVEPRIA
Leukocytosis
  • White blood cell counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim products
  • Monitoring of complete blood count (CBC) during NYVEPRIA therapy is recommended
Thrombocytopenia
  • Thrombocytopenia has been reported in patients receiving pegfilgrastim products
  • Monitor platelet counts
Capillary Leak Syndrome (CLS)
  • CLS has been reported after granulocyte-colony stimulating factor (G‐CSF) administration, including pegfilgrastim products, and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration
  • Episodes vary in frequency and severity and may be life‐threatening if treatment is delayed
  • Patients who develop symptoms of CLS should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care
Potential for Tumor Growth Stimulatory Effects on Malignant Cells
  • The G-CSF receptor through which pegfilgrastim and filgrastim products act has been found on tumor cell lines
  • The possibility that pegfilgrastim products act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer
  • MDS and AML have been associated with the use of pegfilgrastim products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer
  • Monitor patients for signs and symptoms of MDS/AML in these settings
Aortitis
  • Aortitis has been reported in patients receiving pegfilgrastim products. It may occur as early as the first week after start of therapy
  • Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, c-reactive protein and white blood cell count)
  • Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue NYVEPRIA if aortitis is suspected
Nuclear Imaging
  • Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results
Most Common Adverse Reactions
  • Bone pain
  • Pain in extremity

NYVEPRIA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Limitations of Use

NYVEPRIA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Please see full Prescribing Information, Patient Information, and Instructions for Use for NYVEPRIA.

Indication

NYVEPRIA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

 
Limitations of Use
 

NYVEPRIA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Please see full Prescribing Information, Patient Information, and Instructions for Use for NYVEPRIA.