Delving into the Latest Updates on Darinaparsin with Synapse

Author: Nagahama, Fumiko ; Terui, Yasuhito ; Kwong, Yok-Lam ; Tobinai, Kensei ; Uchida, Toshiki ; Yamamoto, Kazuhito ; Sonehara, Yusuke ; Nagai, Hirokazu ; Yoon, Dok-Hyun ; Tien, Hwei-Fang ; Ando, Kiyoshi ; Izutsu, Koji ; Negoro, Eiju ; Suehiro, Youko ; Fukuhara, Noriko ; Kang, Hye Jin ; Nakajima, Hideaki ; Kim, Won-Seog ; Ko, Po-Shen

Abstract:

Darinaparsin is a novel organic arsenical compound of dimethylated arsenic conjugated to glutathione, with antitumor activity and a mechanism of action markedly different from other available agents. This phase 2, nonrandomized, single-arm, open-label study evaluated the efficacy and safety of intravenous darinaparsin (300 mg/m2 over 1 hour, once daily for 5 consecutive days, per 21-day cycle) and its pharmacokinetics at multiple doses in 65 Asian patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The primary end point was the overall response rate (ORR). The ORR based on central assessment was 19.3% (90% confidence interval, 11.2-29.9), which was significantly higher than the predefined threshold of 10% (P = .024). The ORR was 16.2% in patients with PTCL–not otherwise specified and 29.4% in patients with angioimmunoblastic T-cell lymphoma. Tumor size decreased in 62.3% of patients. Treatment-emergent adverse events (TEAEs) were observed in 98.5% of patients. Grade ≥3 TEAEs with an incidence rate of ≥5% included anemia (15.4%), thrombocytopenia (13.8%), neutropenia (12.3%), leukopenia (9.2%), lymphopenia (9.2%), and hypertension (6.2%). Darinaparsin is effective and well tolerated, with TEAEs that were clinically acceptable and manageable with symptomatic treatment and dose reductions. This trial was registered at www.clinicaltrials.gov as #NCT02653976.

01 Apr 2023·Acta pharmacologica Sinica

Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors

Article

Author: Zhang, Zong-Hui ; Hua, Jing-Han ; Cao, Guo-Zhen ; Lv, Yang ; Zhang, Jia-Hui ; Lin, Wen-Chu ; Wang, Xiao-Lin ; Ou, Jian ; Zhang, Shao-Bo ; Ma, Li-Ying

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G₂/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC₅₀ values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.

1

News (Medical) associated with Darinaparsin

05 Jul 2022

·www.prnewswire.com

Brand Institute Partners on Brand Name Development for Treatment of Relapsed or Refractor Peripheral T-Cell Lymphoma Now Approved by Ministry of Health, Labour and Welfare (Japan)

MIAMI, July 5, 2022 /PRNewswire/ -- Brand Institute is proud to announce its work with Solasia Pharma K.K. ("Solasia") in developing the brand name DARVIAS®. DARVIAS®, an organoarsenic compound with anticancer activity, is a novel mitochondrial-targeted agent being developed for the treatment of various hematologic and solid tumors. DARVIAS® provokes cell cycle arrest and apoptosis through disruption of mitochondrial functions and increased production of reactive oxygen species in tumor cells. DARVIAS® is expected to exert an anticancer effect by inducing cell cycle arrest and apoptosis. DARVIAS® has been approved for relapsed or refractory Peripheral T-Cell Lymphoma by Japan's Ministry of Health, Labour and Welfare (MHLW). Japan is the first country in the world where DARVIAS® has been approved. DARVIAS® has been granted orphan drug designation in the US and EU. "The entire Brand Institute and Drug Safety Institute team congratulates Solasia on the MHLW approval of the DARVIAS injection," said Brand Institute's Chairman and C.E.O., James L. Dettore. About Brand Institute and our wholly owned regulatory subsidiary, Drug Safety Institute Brand Institute is the global leader in pharmaceutical and healthcare-related name development, with a portfolio of over 3,800 marketed healthcare brand names, 1,200 USAN/INN nonproprietary names for 1,100 clients. The company partners on over 75% of pharmaceutical brand and nonproprietary name approvals globally every year with healthcare manufacturers. Drug Safety Institute is composed of former naming regulatory officials from global government health agencies, including Food and Drug Administration (FDA), European Medicines Agency (EMA), Health Canada (HC), American Medical Association (AMA), and the World Health Organization (WHO). These regulatory experts co-authored the name review guidelines while with their respective agencies, with many responsible for ultimately approving (or rejecting) brand name applications. Now working for a private company, these professionals provide Brand Institute's clients with industry-leading guidance pertaining to drug name safety (i.e., preventing medication errors), packaging, and labeling. Contact: James Dettore Chairman & C.E.O. [email protected] SOURCE Brand Institute, Inc.

Orphan Drug

100 Deals associated with Darinaparsin

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KEGG	Wiki	ATC	Drug Bank
D08898	-	-	DB06179

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Peripheral T-Cell Lymphoma	Japan	Solasia Pharma KK	20 Jun 2022
Peripheral T-Cell Lymphoma	Japan	Nippon Kayaku Co., Ltd.	20 Jun 2022

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Jan 2007
Bone Marrow Neoplasms	Phase 2	United States	Alaunos Therapeutics, Inc.	01 Dec 2006
Multiple Myeloma	Phase 2	Canada	Alaunos Therapeutics, Inc.	01 Jan 2006
Hepatocellular Carcinoma	Phase 2	-	Meiji Seika Pharma Co., Ltd.	-
Lymphoma	Phase 1	-	Alaunos Therapeutics, Inc.	01 Jun 2010
Advanced cancer	Phase 1	United States	Alaunos Therapeutics, Inc.	01 Aug 2007
Advanced Malignant Solid Neoplasm	Phase 1	United States	Alaunos Therapeutics, Inc.	01 May 2005
Myelodysplastic Syndromes	Phase 1	United States	Alaunos Therapeutics, Inc.	01 May 2005
Myeloproliferative Disorders	Phase 1	United States	Alaunos Therapeutics, Inc.	01 May 2005
Recurrent Acute Leukemia	Phase 1	United States	Alaunos Therapeutics, Inc.	01 May 2005

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02653976 (CTgov)	Phase 2	Peripheral T-Cell Lymphoma	67	SP-02L (darinaparsin for injection)	mycstfwbci = lkjhuudgxk pgtswkuybn (jomgdgulhz, mrtkadnvih - sndhebuhbi) View more	-	26 Jan 2024
NCT02653976 (Pubmed)	Phase 2	Peripheral T-Cell Lymphoma	65	Darinaparsin	sdjguhijjc(wyjmekfnbm) = ecidkjsjoa ejifulbxuj (cvtdctylxk, 11.2 - 29.9)	Positive	20 Jan 2023
NCT01689220 \| NCT01435863 (Pubmed \| Jpn J Clin Oncol) Manual	Phase 1	Peripheral T-Cell Lymphoma	23	Darinaparsin	sanhvsrjtf(itotfmalwe) = lymphopenia (9%), neutropenia (9%) and thrombocytopenia (9%) lgawyddhni (dvtnjjiple )	Positive	08 Feb 2021
NCT02653976 (Biospace) Manual	Phase 2	Peripheral T-Cell Lymphoma	-	DARINAPARSIN	thugydcvit(zrbyhkhxmh) = reach whpofrnwlt (usqgmnpqkz ) View more	Positive	15 Jun 2020
NCT00509782 (Pubmed \| Clin Cancer Res)	Phase 1	Solid tumor	47	Darinaparsin	hcaizctdjm(byiligcswl) = lfrezbhntf qddlkfrmgq (snmmzbfhxc ) View more	-	15 Jul 2009
ASCO2009	Phase 2	Advanced Hepatocellular Carcinoma	15	Darinaparsin	ossmpsovfc(qxowieqsgl) = gizyxgftha gusjahcjnm (ailyfwmfhn, 93 - 227) View more	Negative	20 May 2009
ASCO2007	Phase 1/2	Multiple Myeloma	19	ZIO-101 daily for 5 consecutive d every 4 w	ffiuvhkmsz(wzavbgvaxu) = transient confusion /ataxia laziffbyky (rjriqlyyik )	-	20 Jun 2007
ASCO2007	Phase 1	HR-positive/HER2-low Solid Tumors	34	ZIO-101	kccdysjwwk(rxkwjkfzeb) = transient confusion, and ataxia phygvvoctg (rqrwnrvtoz ) View more	-	20 Jun 2007
Tandem Meetings ASTCT and CIBMTR2007	Phase 1/2	Multiple Myeloma	13	ZIO-101	oubhpppiwp(oarsexxerk) = cjknkipczn odyyphiidp (oqwgutquxa, 0.8) View more	Positive	01 Feb 2007
ASCO2006	Phase 1	Hematologic Neoplasms	8	ZIO-101	vnuhomfrcx(ztlmsdpacz) = bqqatlnrxw puxqlbnyqq (sfseexlrcu ) View more	-	20 Jun 2006