Mylan and Biocon’s Fulphila ™ – First Biosimilar to Pegfilgrastim (Neulasta®)

New Drug Overview: Pegfilgrastim-jmdb (Fulphila™)

The first FDA approved biosimilar to Pegfilgrastim (Neulasta®)

Generic Name Brand Name Manufacturer Approval Date Anticipated Availability Accelerated Review
Pegfilgrastim-jmdb Fulphila ™ Mylan GmbH June 4, 2018 In the coming weeks n/a
Labeled Indication:
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.
Limitation of Use – Fulphila™ is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
Drug Class: Comparative Drugs in Class:
Granulocyte colony-stimulating factors (G-CSFs) Neulasta (pegfilgrastim), Neupogen/Zarxio (filgrastim), Granix (tbo-filgrastim)
Mechanism of Action:
Act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation
Clinical Trial Summary:
Package insert safety data is based upon 932 patients receiving pegfilgrastim in seven randomized clinical trials.  The population was 21 to 88 years of age and 92% female, with most patients receiving a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

 

There are multiple randomized, double-blind, controlled studies reported in the package insert specific to the approved indication.

 

Studies 1 and 2

Chemotherapy: doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 administered every 21 days for up to 4 cycles for the treatment of metastatic breast cancer

Study 1: pegfilgrastim single fixed dose (6 mg) on day 2 verses daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day 2

Study 2: pegfilgrastim weight-adjusted dose (100mcg/kg) verses daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day 2

Primary endpoint: duration of severe neutropenia

Efficacy measure: comparability to filgrastim-treated patients in the mean days of severe neutropenia

Reported Outcome: the mean days of severe neutropenia of pegfilgrastim-treated patients did not exceed that of filgrastim-treated patients by more than 1 day in cycle 1 of chemotherapy

Study 1: Mean days 1.8 days (pegfilgrastim) verses 1.6 days (filgrastim) [95% CI: -0.2, 0.6]

Study 2: Mean days 1.8 days (pegfilgrastim) verses 1.6 days (filgrastim) [95% CI: -0.2, 0.4]

 

Study 3

Chemotherapy: docetaxel 100 mg/m2 administered every 21 days for up to 4 cycles for the treatment of metastatic or nonmetastatic breast cancer

Study 3: pegfilgrastim (6 mg) or placebo on day 2 of each chemotherapy cycle

Primary endpoint: incidence of febrile neutropenia as compared to placebo

Efficacy measure: comparability to filgrastim-treated patients in the mean days of severe neutropenia

Reported Outcome: febrile neutropenia defined as temperature ≥ 38.2°C and ANC ≤ 0.5 x109 /L

Study 3: 1% (pegfilgrastim) versus 17% (placebo), p < 0.001

 

Study 4

Pediatric: Multicenter, randomized, open-label study open to patients with sarcoma receiving chemotherapy age 0 to 21 years.

Study 4: Pegfilgrastim dose (100mcg/kg) verses filgrastim (5 mcg/kg/day) following myelosuppressive chemotherapy

Reported Outcome: neutrophil counts recovery was similar in both groups

Warnings and Adverse Effects (AE):
Warning: (Serious side effects) rupture of the spleen, acute respiratory distress syndrome (ARDS), serious allergic reactions including anaphylaxis, fatal sickle cell crises, acute inflammation of the kidney (glomerulonephritis), leukocytosis, capillary leak syndrome and tumor growth stimulatory effects on malignant cells
AE: (Most Common) bone pain and pain in extremities
NDC Strength Volume Single Dose/Multi Dose Storage
67457-0833-06 6mg/0.6ml 0.6ml Single-dose syringe Refrigeration
U.S. Drug Sales Forecast (in millions):
2018(F) 2019(F) 2020(F) 2021(F) 2022(F) 2023(F)
Pegfilgrastim-jmdb (Fulphila™) Not Reported
Pegfilgrastim (Neulasta®) 3,696 3,180 2,812 2,532 2,278 2,021

While global data has not provided a sales forecast for Pegfilgrastim-jmdb (Fulphila™), they do note in their December 2017 report PharmacFocus: Supportive Care in Oncology, “Neulasta (pegfilgrastim) represents one of Amgen’s most lucrative products, generating worldwide revenues of $4.648 billion in 2016…”


July Update: RJ Health anticipates CMS will create a Q-code for this drug which will be effective October 1st.


References:

U.S. Food & Drug Administration, FDA News & Events, FDA News Release https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609805.htm   (Accessed 06/05/2018)

Product Labeling https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761075s000lbl.pdf  (Accessed 06/05/2018)

Mylan, News, Press Releases http://newsroom.mylan.com/2018-06-04-U-S-FDA-Approves-Mylan-and-Biocons-Fulphila-TM-pegfilgrastim-jmdb-the-First-Biosimilar-to-Neulasta-R (Accessed 06/05/2018)

RJ Health Systems Web Site https://www.reimbursementcodes.com (Accessed 06/05/2018)

Global Data, Pharma Intelligence Web Site, View Drug Overview Site https://pharma.globaldata.com (Accessed 06/05/2018)


For a review of the 2018 drug pipeline please click here.

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