Delving into the Latest Updates on Donafenib Tosylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Donafenib, Donafenib tosilate, Zeprosen

+ [4]

Target

CRAF x PDGFR x VEGFR

Mechanism

CRAF inhibitors(C-Raf kinase inhibitors), PDGFR antagonists(Platelet-derived growth factor receptor antagonists), VEGFR antagonists(Vascular endothelial growth factor receptor antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Thyroid CancerHepatocellular CarcinomaAdvanced Malignant Solid Neoplasm+ [1]

Inactive Indication

Advanced gastric carcinomaAdvanced Hepatocellular CarcinomaBiliary Tract Neoplasms+ [7]

Originator Organization

Suzhou Zelgen Biopharmaceuticals Co., Ltd.

Active Organization

Suzhou Zelgen Biopharmaceuticals Co., Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (08 Jun 2021),

Hepatocellular Carcinoma

RegulationSpecial Review Project (CN), Priority Review (CN)

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Structure/Sequence

Molecular FormulaC28H24ClF3N4O6S

InChIKeyIVDHYUQIDRJSTI-NIIDSAIPSA-N

CAS Registry1333386-17-6

View All Structures (2)

This study is a randomized, open label, parallel controlled trial aimed at evaluating and observing the efficacy and safety of the combination of donafenib and capecitabine as adjuvant therapy for postoperative treatment of biliary malignancies with high risk of recurrence.
The study selected patients with biliary malignant tumors who are at high risk of postoperative recurrence as the research subjects.
After the subjects sign the informed consent and pass the screening, they will be randomly divided into 1:1 groups. The experimental group consisted of Donafenib (200mg, bid) combined with capecitabine (1250mg/m2, bid, treated for 2 weeks and stopped for 1 week). The control group was capecitabine (1250mg/m2, bid, treated for 2 weeks and stopped for 1 week). Stop treatment until the subject experiences disease recurrence or intolerable toxic side effects.
The primary endpoint of the study was the 1y RFS rate. Plan to include 70 participants.

Start Date15 Nov 2024

Sponsor / Collaborator

Jiangsu Provincial People's Hospital

NCT06646198

/ RecruitingPhase 2IIT

Transjugular Intrahepatic Portosystemic Shunt (TIPS) Plus Half-dose Donafenib (a Kind of Anti-angiogenesis Agents) in Advanced HCC with Tumor Thrombosis-associated Portal Hypertension: a Prospective, Single-arm, Phase II Study. (DoTH Study)

The purpose of this study is to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension.

Start Date08 Oct 2024

Sponsor / Collaborator

Sun Yat-Sen University

NCT06609876

/ RecruitingNot ApplicableIIT

Thermal Ablation Combined With Low-dose Donafinib for Early Recurrent Hepatocellular Carcinoma: a Multicenter Prospective Study

This study intends to evaluate the efficacy and safety of low-dose adjuvant donafenib after thermal ablation for early recurrent HCC within Milan criteria.

Start Date01 Oct 2024

Sponsor / Collaborator

Sun Yat-Sen University

[+1]

100 Clinical Results associated with Donafenib Tosylate

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100 Translational Medicine associated with Donafenib Tosylate

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100 Patents (Medical) associated with Donafenib Tosylate

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12

Literatures (Medical) associated with Donafenib Tosylate

01 Sep 2023·Journal of Chromatography B

Simultaneous quantification of donafenib, sorafenib, and their N-oxide metabolites in rat plasma using a HPLC-MS/MS method

Article

Author: Hu, Qing ; Zheng, Xiaowei ; Gu, Jinping ; Bao, Meihua ; Liu, Yujia ; Zhang, Yiwen ; Chai, Yitao ; Qin, Hui ; Hu, Ying ; Sun, Zhiyong ; Lou, Yutao

Donafenib and sorafenib are small molecule chemotherapy drugs for the management of hepatocellular carcinoma, with donafenib being a deuterated derivative of sorafenib. To date, a high liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that quantify donafenib, sorafenib, and their main metabolites has not yet been developed. The objective of this study was to establish a HPLC-MS/MS method for the simultaneous detection of donafenib, donafenib-N-oxide, sorafenib, and sorafenib-N-oxide and for the pharmacokinetic studies in rat. The extraction of all analytes was achieved by simple protein precipitation utilizing acetonitrile. The Waters XBridge C₁₈ column (2.1 × 100 mm, 3.5 µm) was selected, and the analytes could be efficiently separated and quantitated during a 2.8 min gradient elution procedure. The method was linear within the predefined quantification ranges and provided acceptable precision (%CV < 9.4%), reproducible extraction recovery (99.4%-111.5%), and low matrix effect (88.1%-98.6%). The hemolysis effect did not interfere with the quantification of all analytes, and similar results were obtained by changing the anticoagulant K₂-EDTA to heparin or sodium citrate. Plasma pharmacokinetics revealed that the values of t_1/2, C_max, and AUC_0-t of donafenib were 1.4-, 6.2-, and 3.1-fold higher than those of sorafenib, respectively. In conclusion, the proposed bioassay was successfully applied to pharmacokinetic studies in rat after administration of donafenib and sorafenib. Our work not only improves the bioanalytical method for determining the plasma concentrations of donafenib, sorafenib, and their N-oxide metabolites, but also provides a scientific reference for clinical pharmacokinetic studies.

01 Jun 2023·Biomedicine & Pharmacotherapy

In vivo assessment of the pharmacokinetic interactions between donafenib and dapagliflozin, donafenib and canagliflozin in rats

Article

Author: Li, Ying ; He, Xueru ; Li, Yajing ; Dong, Zhanjun ; Fu, Yuhao ; Guo, Caihui ; Xun, Xuejiao ; Wang, Zhi

Donafenib (DONA), a deuterium derivative of sorafenib, is used for advanced hepatocellular carcinoma (HCC). Dapagliflozin (DAPA) and canagliflozin (CANA) are sodium-glucose co-transporter 2 (SGLT2) inhibitors used for T2DM, which is frequently comorbid with HCC. Three drugs are substrates of UGT1A9 isoenzyme. This study aimed to evaluate donafenib-dapagliflozin and donafenib-canagliflozin pharmacokinetic interactions and explore the potential mechanisms. Rats were divided into seven groups (n = 6) that received donafenib (1), dapagliflozin (2), canagliflozin (3), dapagliflozin and donafenib (4), canagliflozin and donafenib (5), donafenib and dapagliflozin (6), donafenib and canagliflozin (7). The concentrations of drugs were determined by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The messenger RNA (mRNA) expressions were measured by quantitative RT-PCR. Multiple doses of dapagliflozin caused donafenib maximum plasma concentration (C_max) to increase 37.01%. Canagliflozin increased donafenib C_max 1.77-fold and the area under the plasma concentration-time curves (AUC_0-t and AUC_inf) 1.39- and 1.41-fold, respectively, while reducing the apparent clearance (CL_z) 28.38%. Multiple doses of donafenib increased dapagliflozin AUC_0-t 1.61-fold, AUC_inf 1.77-fold, whereas its CL_z reduced 40.50%. Furthermore, donafenib caused similar changes in canagliflozin pharmacokinetics. The PCR results demonstrated that dapagliflozin inhibited the mRNA expression of Ugt1a7 in liver and donafenib decreased the expression of Ugt1a7 mRNA in liver and intestine. Increased exposure to these drugs may be due to their metabolism inhibition mediated by Ugt1a7. These pharmacokinetic interactions observed in this study may be of clinical significance, which may help adjust dose properly and avoid toxicity effects in patients with HCC and T2DM.

01 Jan 2023·PloS one

First-line systemic treatment strategies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

Article

Author: Wan, Xiaomin ; Li, Sini ; Zeng, Xiaohui ; Liu, Qiao ; wang, Liting ; Peng, Ye ; Tan, Chongqing ; Qin, Shuxia

BACKGROUNDOral multikinase inhibitors and immune checkpoint inhibitors (ICIs) are effective for treating advanced hepatocellular carcinoma (aHCC) but may increase cost. This study compared the cost-effectiveness of oral multikinase inhibitors and ICIs in the first-line treatment of patients with aHCC.METHODSA three-state Markov model was established to study the cost-effectiveness of drug treatment from the perspective of Chinese payers. The key outcomes in this study were total cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER).RESULTSThe total costs and QALYs of sorafenib, sunitinib, donafenib, lenvatinib, sorafenib plus erlotinib, linifanib, brivanib, sintilimab plus IBI305, and atezolizumab plus bevacizumab were $9070 and 0.25, $9362 and 0.78, $33,814 and 0.45, $49,120 and 0.83, $63,064 and 0.81, $74,814 and 0.82, $81,995 and 0.82, $74083 and 0.85, and $104,188 and 0.84, respectively. The drug regimen with the lowest ICER was sunitinib ($551 per QALY), followed by lenvatinib ($68,869 per QALY). For oral multikinase inhibitors, the ICER of lenvatinib, sorafenib plus erlotinib, linifanib and brivanib compared with sunitinib was $779576, $1534,347, $1768,971, and $1963,064, respectively. For ICIs, sintilimab plus IBI305 is more cost effective than atezolizumab plus bevacizumab. The model was most sensitive to the price of sorafenib, the utility of PD, and the price of second-line drugs.CONCLUSIONFor oral multikinase inhibitors, the order of possible treatment options is sunitinib > lenvatinib > sorafenib plus erlotinib > linifanib > brivanib > donafenib. For ICIs, the order of possible treatment options is sintilimab plus IBI305 > atezolizumab plus bevacizumab.

1

News (Medical) associated with Donafenib Tosylate

04 Aug 2021

·www.mobihealthnews.com

Digital health platform 111 signs deal to build online liver cancer management platform

Nasdaq-listed 111, a Chinese healthcare platform, has entered into a strategic cooperation agreement with Jiangsu-based drug R&D firm Suzhou Zelgen Biopharmaceuticals Co. to build a virtual platform for liver cancer patients. WHAT IT DOES 111 operates an internet hospital offering virtual health consultations, an electronic prescription service, and a patient management service. It also runs one of China's largest retail pharmacy networks serving over 320,000 pharmacies, as well as a medicine marketplace where pharmacies can source products. Moreover, 111 provides an omnichannel commercialisation platform for pharmaceutical firms. WHY IT MATTERS 111 claims that its upcoming online disease management platform will offer liver cancer patients with integrated services, including online consultations and information on diseases, medications and therapies. Additionally, this latest partnership will see Zelgen's flagship product Zeprosyn – a drug for treating unresectable hepatocellular carcinoma, marketed through the platform. Liver cancer is the second leading cause of cancer deaths in China. Data from the WHO's International Agency for Research on Cancer shows that liver cancer accounts for about 410,000 new cancer cases in China last year, causing around 390,000 deaths. THE LARGER TREND In May, 111 also made a similar deal with another biotech firm, BeiGene, to launch an online oncology management platform leveraging its internet hospital capabilities. 111 said it has so far made 360 direct partnerships with pharma companies, such as Eli Lilly and Bayer Healthcare. ON THE RECORD "The cooperation with Zelgen in the field of liver cancer is an important deployment of our digital platform in health management services directed toward a leading cause of cancer death in China. By harnessing the power of the internet, we can break the limitations of time and space, and this new virtual platform will bring together specialists and patients online to efficiently carry out diagnoses, treatment education, follow-up visits and prescription renewals. These functions not only expand the service radius of doctors but also help medicines like Zeprosyn reach more patients," Dr Yu Gang, co-founder and executive chairman of 111, stated. "Through this partnership, we will be able to take advantage of 111's online diagnosis, treatment, multi-channel platform and health management services to further increase the availability of new drugs and, in turn, provide greater benefits to patients," Zelgen Chairman and General Manager Dr Sheng Zelin also commented.

Collaborate

100 Deals associated with Donafenib Tosylate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	L01X	DB15414

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Thyroid Cancer	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	10 Aug 2022
Hepatocellular Carcinoma	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	08 Jun 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	10 May 2024
Refractory Thyroid Gland Carcinoma	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	29 Aug 2018
Refractory Differentiated Thyroid Gland Carcinoma	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	26 Jul 2018
Nasopharyngeal Carcinoma	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	08 Feb 2017
Advanced gastric carcinoma	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	16 May 2016
Metastatic gastric adenocarcinoma	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	16 May 2016
Esophageal Carcinoma	Phase 2	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	21 Jul 2015
Biliary Tract Neoplasms	Discovery	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	01 Dec 2020
Metastatic Colorectal Carcinoma	Discovery	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	28 Dec 2016
Advanced Hepatocellular Carcinoma	Discovery	CN	Suzhou Zelgen Biopharmaceuticals Co., Ltd.	01 Mar 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05668884 (ESMO_ASIA2024) Manual	Phase 2	Advanced biliary tract cancer First line	23	Tislelizumab + donafenib + GEMOX	(fwqeupadhs) = zrimkotasc xuwlmdflnz (rogaheaboj ) View more	Positive	07 Dec 2024
NCT05348811 (ESMO_ASIA2024) Manual	Phase 2	Unresectable Intrahepatic Cholangiocarcinoma First line	21	donafenib + sintilimab + GEMOX-HAIC	(dnhwinltov) = hjwfdhudxs mphaqnblie (blhytlxwdd, 18.1% - 61.6) View more	Positive	07 Dec 2024
NCT04962958 (ASCO2024) Manual	Phase 2	Hepatocellular Carcinoma Adjuvant	18	HAIC-FOLFOX4 + Donafenib	(gdbhckbexc) = moxfhthxil swjvnawbwr (dksemtmzeb, 39.2 - 100) View more	Positive	24 May 2024
ASCO2024 Manual	Not Applicable	Hepatocellular Carcinoma First line	102	donafenibIC	(ktbzoalppj) = ncbxopxntf lqqglhzyjs (obyzdublzn ) View more	Positive	24 May 2024
NCT04418401 (PATH study, ASCO2024)	Phase 1	Hepatocellular Carcinoma Adjuvant	30	Donafenib plus anti-PD-1 antibody	uaznhbykfa(bahcfohaeb) = tpvvxgmttr pypfkvmjhh (nmypkpxxpp, 70.6% - 96.7)	Positive	24 May 2024
NCT02645981 (ZGDH3, ASCO2024)	Phase 3	Unresectable Hepatocellular Carcinoma First line	48	Donafenib combined with anti-PD-1 antibodies	(nilrwqldqa) = jiucolsath gerjfednxs (iinbqindim, 8.9 - NA) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Hepatocellular Carcinoma Adjuvant AFP \| PIVKA-II	82	Donafenib	(xqdgildhwt) = sedolmnczh utlaborsjf (upncvrpfgy ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	Hepatocellular Carcinoma	-	Donafenib 100mg bid	apuckmtjso(oealplzcfk) = AEs occurred in 44 patients, including 39 with grade 1 or 2 AEs and 5 with grade 3 AEs. The most common AEs included hand-foot skin reaction, decreased platelet count, and diarrhea dyyxxlccqq (ywahvibcxk )	-	24 May 2024
NCT05166772 (DoHAICs, ESMO 12023 \| ESMO 22023) Manual	Phase 2	Unresectable Hepatocellular Carcinoma	30	donafenib + sintilimab +oxaliplatin + leucovorin +fluorouracil	(geoowpvzpu) = hgaycqghen vorlecbvvn (ezisdpzffp ) View more	Positive	23 Oct 2023
NCT05166772 (DoHAICs, ESMO 12023 \| ESMO 22023) Manual	Phase 2	Unresectable Hepatocellular Carcinoma	30	donafenib + sintilimab +oxaliplatin + leucovorin +fluorouracil (received hepatectomy)	fjpvcnphxt(vyvyzpwqsz) = pclufldctk skqulnnkmy (mtowwpimxz ) View more	Positive	23 Oct 2023
NCT04418401 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	Hepatocellular Carcinoma Adjuvant	23	donafenib+Toripalimab	xvswtvkxga(vlnmlbrddr) = cqntzttyid uoltdwyvlx (pfmjxjakrv, 61.6 - 93.1) View more	Positive	31 May 2023