Filgrastim
is a recombinant, non-pegylated human granulocyte colony stimulating factor
(G-CSF) analogue manufactured by recombinant DNA technology using a strain of
E. coli. Filgrastim is a 175 amino acid chain with molecular weight of 18,800
daltons. The protein has an amino acid sequence that is identical to the
natural sequence predicted from human DNA sequence analysis, except for the
addition of an N-terminal methionine necessary for expression in E. coli [1].
The
amino acid sequence is:
MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA
PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ
QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQP
Filgrastim
is used to treat neutropenia [a condition of an abnormally low number of neutrophils
(white blood cells)] stimulating the bone marrow to increase production of
neutrophils.
Filgrastim
is indicated for the following:
1. Cancer
Patients Receiving Myelosuppressive Chemotherapy: To decrease the incidence of
infection, as manifested by febrile neutropenia, in patients with non-myeloid
malignancies receiving myelosuppressive anti-neoplastic drugs. It can also used
for pediatric patients.
2. Patients
with Acute Myeloid Leukemia: For the reduction in the duration of neutropenia,
fever, antibiotic use and hospitalization.
3. Cancer
Patients Receiving Myeloablative Chemotherapy Followed by Bone Marrow
Transplantation: To reduce the duration
of neutropenia and neutropenia-related clinical sequelae.
4. Patients
with Severe Chronic Neutropenia (SCN): To increase neutrophil counts and to
reduce the incidence and duration of infection in patients with a diagnosis of
congenital, cyclic or idiopathic neutropenia.
5. Patients
with HIV Infection: For the prevention
and treatment of neutropenia.
Filgrastim
is marketed under several brand names, including: Neupogen (Amgen), Filcad
(Cadila Pharma), Nufil (Biocon), etc.
On March 6, 2015, the U. S. Food and Drug
Administration approved filgrastim-sndz (ZARXIO Injection, Sandoz Inc.), as a
biosimilar to US-licensed Neupogen for the five indications for which
US-licensed Neupogen is approved. The formulation of ZARXIO differs from that
of US-licensed Neupogen in one inactive component.
On
March 30, 2015, FDA approved use of Neupogen (filgrastim) to treat adult and
pediatric patients acutely exposed to myelosuppressive doses of radiation
(Hematopoietic Syndrome of Acute Radiation Syndrome, or H-ARS).
Myelosuppression occurs when radiation damages internal organs, including bone
marrow. Suppression of the bone marrow blocks the production of blood cells.
Neupogen can help patients with H-ARS by facilitating recovery of bone marrow
cells that develop into white blood cells, including neutrophils, that help
fight off infections. It was approved by FDA based on studies in animals (under
the Animal Rule), as studies in humans could not be ethically conducted.
In
addition, orphan drug designation was granted for this indication, and this
supplemental application received priority review.
The
drug, Neupogen, is the first ever approved for the treatment of acute radiation
injury.
About
Acute Radiation Syndrome [2]
Acute
Radiation Syndrome is an acute illness caused by irradiation of the entire body
(or most of the body) by a high dose of penetrating radiation in a short period
of time, usually a matter of minutes.
Patients
exposed to high doses of radiation will not be able to produce sufficient
numbers of new white blood cells, red blood cells, and platelets, a condition
called myelosuppression. Two major clinical manifestations of radiation bone
marrow injury are neutropenia (abnormally low level of neutrophils, a type of
white blood cell) and thrombocytopenia (abnormally low level of platelets) that
directly impact the survival of victims exposed to radiation. Severe
neutropenia increases the risk of sepsis and death due to infections, while
thrombocytopenia increases the risk of hemorrhage and death due to bleeding.
Until
patients' bone marrow recovers and creates enough new blood cells-a slow
process-these patients are at a high risk of death from infection and bleeding.
Neupogen can effectively reduce the duration and severity of neutropenia and
increase survival.
References:
1. Ahmed, K. E.; et. al. Complete sequencing of the recombinant granulocyte-colony
stimulating factor (filgrastim) and detection of biotinylation by mass
spectrometry. Amino Acids 2010, 38(4), 1043-1049.
