Delving into the Latest Updates on Filgrastim biosimilar(Dong-A Pharmaceutical Co., Ltd.) with Synapse

Overview

Basic Info

Drug Type

Biosimilar, Colony-stimulating factors

Synonyms

Filgrastim biosimilar, Leucostim, Leukopoeitin

+ [4]

Target

CSF-3R

Mechanism

CSF-3R agonists(Colony stimulating factor 3 receptor agonists)

Therapeutic Areas

Hemic and Lymphatic Diseases

Active Indication

Neutropenia

Inactive Indication

Diabetic peripheral neuropathic pain

Originator Organization

Dong-A Pharmaceutical Co., Ltd.

Active Organization

Dong-A Pharmaceutical Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

KR (07 Jun 1995),

Neutropenia

Regulation-

Login to view timeline

Gene Sequence

Sequence Code 4190

The sequence is quoted from: *****

Severe congenital neutropenia (CN) is an inherited pre-leukemia bone marrow failure syndrome commonly caused by autosomal-dominant ELANE mutations (ELANE-CN). ELANE-CN patients are treated with daily injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF). However, some patients do not respond to rhG-CSF, and approximately 15% of ELANE-CN patients develop myelodysplasia or acute myeloid leukemia. Here, we report the development of a curative therapy for ELANE-CN through inhibition of ELANE mRNA expression by introducing two single-strand DNA breaks at the opposing DNA strands of the ELANE promoter TATA box using CRISPR-Cas9D10A nickases-termed MILESTONE. This editing effectively restored defective neutrophil differentiation of ELANE-CN CD34⁺ hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, without affecting the functions of the edited neutrophils. CRISPResso analysis of the edited ELANE-CN CD34⁺ HSPCs revealed on-target efficiencies of over 90%. Simultaneously, GUIDE-seq, CAST-Seq, and rhAmpSeq indicated a safe off-target profile with no off-target sites or chromosomal translocations. Taken together, ex vivo gene editing of ELANE-CN HSPCs using MILESTONE in the setting of autologous stem cell transplantation could be a universal, safe, and efficient gene therapy approach for ELANE-CN patients.

01 Apr 2024·Indian Journal of Hematology and Blood Transfusion

The Effectiveness and Optimal Timing of PEG-rhG-CSF After Autologous Peripheral Blood Stem Cell Transplantation: A Multicenter Experience

Article

Author: Liu, Hui ; Dong, Fei ; Yang, Ping ; Jing, Hongmei ; Li, Jiangtao ; Li, Sen

No consensus has been made on the use of PEG-modification recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in patients receiving autologous peripheral blood stem cell transplantation (PBSCT). To evaluate the efficacy and safety of PEG-rhG-CSF in provision of neutrophil support for lymphoma patients receiving autologous PBSCT. This retrospective study included lymphoma patients receiving either PEG-rhG-CSF or rhG-CSF after autologous PBSCT from 2018 to 2021 in two clinics. Hematologic recovery time, incidence of infectious complications and toxicity were compared between these two rhG-CSFs and among different initiation time of PEG-rhG-CSF. Of the 139 subjects included, 93 received PEG-rhG-CSF and 46 received rhG-CSF after transplantation. Compared with rhG-CSF, PEG-rhG-CSF marginally but significantly accelerated the neutrophil engraftment by 1 day (10 vs. 9 days, respectively) with no increasing on the risk of infectious complication and toxicity. In the PEG-rhG-CSF group, 50 patients received the growth factor on day 1, 19 received on day 3 and 24 received on day 5. The neutrophil engraftment was significantly shorter in day 1 and day 3 subgroup (9, 9, and 10 days, respectively), with a lower incidence of febrile neutropenia (82%, 100%, 100%) and documented infections (76%, 100%, 100%) in day 1 subgroup. PEG-rhG-CSF might be an alternative to rhG-CSF for lymphoma patients received autologous PBSCT. Administrating PEG-rhG-CSF on day 1 can achieve both faster hematologic recovery and lower infectious complications.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12288-023-01704-8.

01 Apr 2024·Biochemical and Biophysical Research Communications

Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production

Article

Author: Zhao, Zhenhu ; Wang, Shaozheng ; Zhang, Hong ; Wang, Junke ; Meng, Ruoxi ; Li, Zhongtang ; Liu, Xiaoyan ; Jin, Yiguang ; Liu, Xiaolan ; Zuo, Zongchao ; Ouyang, Zhangyi ; Wang, Limei ; Liu, Xinyu ; Cong, Yuwen ; Shan, Yajun

To date only four recombinant growth factors, including Filgrastim (rhG-CSF), have been approved by FDA as radiomitigators to ameliorate hematopoietic acute radiation syndrome (H-ARS). These approved agents are not stable under room-temperature, needing to be stored at 2-8 °C, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (δ-T3H), the most potent G-CSF-inducing agent among vitamin E isoforms, exhibited efficiency and selectivity on G-CSF production in comparison with TLR and STING agonists in mice. Five-dose δ-T3H was utilized as the optimal therapeutic regimen due to long-term G-CSF production and the best peripheral blood (PB) recovery of irradiated mice. Comparable with rhG-CSF, sequential administration of δ-T3H post-irradiation improved hematologic recovery and accelerated the regeneration of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow (BM) and spleen of 6.5Gy irradiated mice; and consistently enhanced repopulation of BM-HSCs. In 4.0Gy irradiated nonhuman primates, δ-T3H exhibited comparable efficacy as rhG-CSF to promote PB recovery and colony-formation of BM-HPCs. Altogether, we demonstrated that sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production, indicated δ-T3H as a promising radiomitigator for the management of H-ARS, particularly in a mass casualty scenario.

100 Deals associated with Filgrastim biosimilar(Dong-A Pharmaceutical Co., Ltd.)

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L03AA02	-

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Neutropenia	KR	Dong-A Pharmaceutical Co., Ltd.	07 Jun 1995

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Diabetic peripheral neuropathic pain	Preclinical	KR	Dong-A Pharmaceutical Co., Ltd.	01 Jun 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


P304 (EBMT2023)	Not Applicable	Myeloid Tumor Maintenance	24	rhG-CSF+Decitabine	(ijfbvrgcmi) = hjoetvqzbt emtpurwiso (roowpavrit, 9.57 - NA)	-	23 Apr 2023
EHA2015	Not Applicable	-	29	Biosimilar filgrastim (Leucostim®)	ogtlptmqjd(lwwnnysbqa) = uwcpboqght eiwoerkrjd (myqzxrgkht ) View more	-	21 May 2015
EHA2015	Not Applicable	-	29	Lenograstim (Granocyte®)	ogtlptmqjd(lwwnnysbqa) = vudlvxqcum eiwoerkrjd (myqzxrgkht ) View more	-	21 May 2015
ASCO2006	Phase 2	Non-small cell lung cancer stage III	22	Induction docetaxel/cisplatin with rhG-CSF	litbyxcvzt(cigzhuemkl) = vyqxhhomuk civzecseaq (dhqlfxwikv ) View more	-	20 Jun 2006
ASCO2006	Phase 2	Non-small cell lung cancer stage III	22	Concurrent pulsed docetaxel chemoradiation	litbyxcvzt(cigzhuemkl) = xjarklkhce civzecseaq (dhqlfxwikv )	-	20 Jun 2006
ASCO2004	Phase 2	Non-small cell lung cancer stage III	15	Induction Docetaxel/Cisplatin with rhG-CSF	(ttisatjmim) = zhhlxnqvij rmnzaloqur (yxrmfppojn )	-	15 Jul 2004