Proven to reduce duration of severe neutropenia1-3

  1. Duration of SN
  2. ANC Profile
  3. Incidence of FN
  4. Cycles 2 to 4
  5. Safety Profile

Demonstrated noninferiority vs pegfilgrastim1-3

Primary endpointMean Duration of Severe Neutropenia (Days) in Cycle 11-3

Chart: Mean Duration of Severe NeutropeniaChart: Mean Duration of Severe Neutropenia

Selected Safety Information

Adverse Reactions

  • Permanent discontinuation due to an adverse reaction occurred in 4% of patients who received ROLVEDON. The adverse reaction requiring permanent discontinuation in 3 patients who received ROLVEDON was rash.

Every day you help a cancer patient avoid severe neutropenia is critical4

Incidence and duration of Severe Neutropenia (DSN) by Day in Cycle 11-3

Chart: Incidence and duration of Severe Neutropenia, Study 1Chart: Incidence and duration of Severe Neutropenia, Study 2
Chart: Incidence and duration of Severe Neutropenia, Study 1

~84% of ROLVEDON patients had no severe neutropenia (compared to ~76% of pegfilgrastim patients)1,2

Chart: Incidence and duration of Severe Neutropenia, Study 2

~80% of ROLVEDON patients had no severe neutropenia (compared to ~77% of pegfilgrastim patients)2,3

Legend visual for study design chart
  • Comparisons were conducted on patients with no SN and on individual days. The data do not support any day-to-day comparison advantages
  • Demonstrated noninferiority vs pegfilgrastim1-3

Selected Safety Information

Adverse Reactions

  • The most common adverse reactions (≥20%) were fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain.

The first long-acting myeloid growth factor in over 20 years with a unique molecular structure

Review Structure/MOA
  1. Duration of SN
  2. ANC Profile
  3. Incidence of FN
  4. Cycles 2 to 4
  5. Safety Profile

ANC profile vs pegfilgrastim 1,2,5

Secondary endpointTime to ANC Recovery (Mean [SD] Days) in Cycle 1*

Study 11,5Study 23,5
Eflapegrastim-xnst
(n=196)		Pegfilgrastim
(n=210)		Eflapegrastim-xnst
(n=118)		Pegfilgrastim
(n=119)
3.24 (3.565)3.49 (3.589)3.49 (3.723)3.35 (3.745)

Depth of ANC Nadir (Mean [SD] ANC x 109/L) in Cycle 1*

Study 15Study 25
Eflapegrastim-xnst
(n=196)		Pegfilgrastim
(n=210)		Eflapegrastim-xnst
(n=118)		Pegfilgrastim
(n=119)
2.56 (3.086)2.53 (3.317)2.67 (3.504)2.06 (2.034)

SD=standard deviation.

  • Time to ANC recovery and depth of ANC nadir were secondary endpoints. The differences did not meet threshold to support statistical significance.

Secondary endpointTime to ANC Recovery (Mean [SD] Days) in Cycle 1*

Study 11,5
Eflapegrastim‑xnst
(n=196)		Pegfilgrastim
(n=210)
3.24 (3.565)3.49 (3.589)
Study 23,5
Eflapegrastim‑xnst
(n=118)		Pegfilgrastim
(n=119)
3.49 (3.723)3.35 (3.745)

Depth of ANC Nadir (Mean [SD] ANC x 109/L) in Cycle 1*

Study 15
Eflapegrastim‑xnst
(n=196)		Pegfilgrastim
(n=210)
2.56 (3.086)2.53 (3.317)
Study 25
Eflapegrastim‑xnst
(n=118)		Pegfilgrastim
(n=119)
2.67 (3.504)2.06 (2.034)

SD=standard deviation.

  • Time to ANC recovery and depth of ANC nadir were secondary endpoints. The differences did not meet threshold to support statistical significance.

Mean ANC Over Time in Cycle 11,3

Chart: Mean ANC Over Time in Cycle in Study 1Chart: Mean ANC Over Time in Cycle in Study 1
Chart: Mean ANC Over Time in Cycle in Study 2Chart: Mean ANC Over Time in Cycle in Study 2
  • All data supporting endpoints were contained within days 5 through 8
  • ANC=absolute neutrophil count; SD=standard deviation.

Selected Safety Information

Leukocytosis

  • White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving rhG-CSF products. Monitor complete blood count (CBC) during ROLVEDON therapy. Discontinue ROLVEDON treatment if WBC count of 100 x 109/L or greater occurs.

Secondary endpointIncidence of febrile neutropenia in cycle 11,3

From a total of 643 patients in both studies, febrile neutropenia was observed in 11 patients in cycle 1.1,3

Chart: The incidence of febrile neutropeniaChart: The incidence of febrile neutropenia
  • The incidence of febrile neutropenia in cycle 1 was a secondary endpoint, the data were insufficient to support statistical analysis.

Selected Safety Information

Sickle Cell Crisis in Patients with Sickle Cell Disorders

  • Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving rhG-CSF products, such as ROLVEDON. Discontinue ROLVEDON if sickle cell crisis occurs.

Efficacy across 4 cycles of chemotherapy1,2,5

Additional secondary endpointMean DSN (Days) in Cycles 2 to 41,2,5

Chart: Mean DSN (Days) in Cycles 2 to 4Chart: Mean DSN (Days) in Cycles 2 to 4
Mean DSN values for cycles 2 to 4 are secondary endpoints with demonstrated noninferiority between treatment arms.

Selected Safety Information

Splenic Rupture

  • Splenic rupture, including fatal cases, can occur following the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) products. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

Proven safety profile2

Common Adverse Reactions with a Frequency of ≥10% Through Week 14 in Patients with Early-Stage Breast Cancer in Study 1 and Study 2

Adverse ReactionROLVEDON (n=314)%Pegfilgrastim** (n=326)%
Fatigue*181 (58%)192 (59%)
Nausea162 (52%)166 (51%)
Diarrhea125 (40%)126 (39%)
Bone pain119 (38%)121 (37%)
Headache*92 (29%)90 (28%)
Pyrexia*87 (28%)84 (26%)
Anemia*77 (25%)52 (16%)
Rash*77 (25%)99 (30%)
Myalgia69 (22%)49 (15%)
Arthralgia66 (21%)48 (15%)
Back pain*63 (20%)55 (17%)
Decreased appetite61 (19%)50 (15%)
Peripheral edema*57 (18%)53 (16%)
Abdominal pain*53 (17%)67 (21%)
Dizziness*50 (16%)38 (12%)
Dyspnea*49 (16%)44 (13%)
Cough*48 (15%)51 (16%)
Thrombocytopenia*44 (14%)17 (5%)
Pain37 (12%)42 (13%)
Pain in extremity36 (11%)42 (13%)
Local administration reactions*34 (11%)27 (8%)
Flushing32 (10%)27 (8%)

*Grouped Terms
**Study 1 and Study 2 were not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the ROLVEDON and the pegfilgrastim treatment groups.

References:

  1. Schwartzberg LS, Bhat G, Peguero J, et al. Eflapegrastim, a long-acting granulocyte-colony stimulating factor for the management of chemotherapy-induced neutropenia: results of a phase III trial. Oncologist. 2020;25(8):e1233-e1241.
  2. ROLVEDON [package insert]. Lake Forest, IL: Spectrum Pharmaceuticals, Inc.
  3. Cobb PW, Moon YW, Mezei K, et al. A comparison of eflapegrastim to pegfilgrastim in the management of chemotherapy-induced neutropenia in patients with early-stage breast cancer undergoing cytotoxic chemotherapy (RECOVER): a phase 3 study. Cancer Med. 2020;9(17):6234–6243.
  4. Li Y, Klippel Z, Shih X, Reiner M, Wang H, Page JH. Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies. Support Care Cancer.2016;24(10):4377-4383.
  5. Data on file. Spectrum Pharmaceuticals, Inc.

The first long-acting myeloid growth factor in over 20 years with a unique molecular structure

Review Structure/MOA

Indication

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

Important Safety Information

Contraindications

  • ROLVEDON is contraindicated in patients with a history of serious allergic reactions to eflapegrastim, pegfilgrastim, or filgrastim products. Reactions may include anaphylaxis.

Indications and Usage

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

Limitations of Use

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

Important Safety Information

Contraindications

  • ROLVEDON is contraindicated in patients with a history of serious allergic reactions to eflapegrastim, pegfilgrastim or filgrastim products. Reactions may include anaphylaxis.

Warnings and Precautions

Splenic Rupture

  • Splenic rupture, including fatal cases, can occur following the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) products. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

Acute Respiratory Distress Syndrome (ARDS)

  • ARDS can occur in patients receiving rhG-CSF products. Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue ROLVEDON in patients with ARDS.

Serious Allergic Reactions

  • Serious allergic reactions, including anaphylaxis, can occur in patients receiving rhG-CSF products. Permanently discontinue ROLVEDON in patients who experience serious allergic reactions.

Sickle Cell Crisis in Patients with Sickle Cell Disorders

  • Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving rhG-CSF products. Discontinue ROLVEDON if sickle cell crisis occurs.

Glomerulonephritis

  • Glomerulonephritis has occurred in patients receiving rhG-CSF products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation. Evaluate and consider dose reduction or interruption of ROLVEDON if causality is likely.

Leukocytosis

  • White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving rhG-CSF products. Monitor complete blood count (CBC) during ROLVEDON therapy. Discontinue ROLVEDON treatment if WBC count of 100 x 109/L or greater occurs.

Thrombocytopenia

  • Thrombocytopenia has been reported in patients receiving rhG-CSF products. Monitor platelet counts.

Capillary Leak Syndrome

  • Capillary leak syndrome has been reported after administration of rhG-CSF 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. If symptoms develop, closely monitor and give standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells

  • The granulocyte colony-stimulating factor (G-CSF) receptor through which ROLVEDON acts has been found on tumor cell lines. The possibility that ROLVEDON acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which ROLVEDON is 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 rhG-CSF 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 rhG-CSF products. It may occur as early as the first week after start of therapy. Consider aortitis in patients who develop generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count) without known etiology. Discontinue ROLVEDON 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.

Adverse Reactions

  • The most common adverse reactions (≥20%) were fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain.
  • Permanent discontinuation due to an adverse reaction occurred in 4% of patients who received ROLVEDON. The adverse reaction requiring permanent discontinuation in 3 patients who received ROLVEDON was rash.

    To report SUSPECTED ADVERSE REACTIONS, contact Assertio Holdings, Inc. at 1‑866‑458‑6389 or FDA at 1‑800‑FDA‑1088 or www.fda.gov/medwatch.

    Please see accompanying full Prescribing Information for ROLVEDON.