Delving into the Latest Updates on Peficitinib Hydrobromide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ASP-015K hydrobromide, Peficitinib, Peficitinib hydrobromide (JAN/USAN)

+ [7]

Target

JAK1 x JAK2 x JAK3 x TYK2

Mechanism

JAK1 inhibitors(Tyrosine-protein kinase JAK1 inhibitors), JAK2 inhibitors(Tyrosine-protein kinase JAK2 inhibitors), JAK3 inhibitors(Tyrosine-protein kinase JAK3 inhibitors)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication

Rheumatoid Arthritis

Inactive Indication

liver function failurePlaque psoriasis

Originator Organization

Astellas Pharma, Inc.

Active Organization

Astellas Pharma, Inc.

Astellas Pharma China, Inc.

Inactive Organization

Astellas Pharma Global Development, Inc.Janssen Research & Development LLC

Drug Highest PhaseApproved

First Approval Date

JP (26 Mar 2019),

Rheumatoid Arthritis

Regulation-

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Structure

Molecular FormulaC18H23BrN4O2

InChIKeyZUVPMAPXNYGJQC-UHFFFAOYSA-N

CAS Registry1353219-05-2

Janus kinases (JAKs) are a family of cytosolic tyrosine kinases that regulate cytokine signal transduction, including cytokines involved in a range of inflammatory diseases, such as RA, psoriasis, atopic dermatitis and IBD. Several small-molecule JAK inhibitors (JAKis) are now approved for the treatment of various immune-mediated inflammatory diseases. There are, however, key differences between these agents that could potentially translate into unique clinical profiles. Each JAKi has a unique chemical structure, resulting in a distinctive mode of binding within the catalytic cleft of the target JAK, and giving rise to distinct pharmacological characteristics. In addition, the available agents have differing selectivity for JAK isoforms, as well as off-target effects against non-JAKs. Other differences include effects on haematological parameters, DNA damage repair, reproductive toxicity and metabolism/elimination. Here we review the pharmacological profiles of the JAKis abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib.

29 Dec 2023·Modern rheumatology case reports

Successful peficitinib monotherapy for the new-onset skin manifestations of rheumatoid vasculitis after long-term treatment with tocilizumab for rheumatoid arthritis

Article

Author: Sekine, Akinari ; Ubara, Yoshifumi ; Ikuma, Daisuke ; Yamanouchi, Masayuki ; Sawa, Naoki ; Mizuno, Hiroki ; Hasegawa, Eiko ; Inoue, Noriko ; Yamaguchi, Yuko ; Oba, Yuki ; Suwabe, Tatsuya ; Takasawa, Yutaka

ABSTRACT:

Rheumatoid vasculitis (RV) is a severe extra-articular systemic manifestation of rheumatoid arthritis (RA). Its prevalence has been decreasing for decades because of improved early diagnosis of RA and advances in RA treatment, but it remains a life-threatening disease. The standard treatment for RV has been a glucocorticoid and disease-modifying antirheumatic drugs. Biological agents, including antitumour necrosis factor inhibitors, are also recommended for refractory cases. However, there are no reports of Janus kinase (JAK) inhibitor use in RV. We experienced a case of an 85-year-old woman with a 57-year history of RA who had been treated with tocilizumab for 9 years after receiving three different biological agents over 2 years. Her RA seemed to be in remission in her joints, and her serum C-reactive protein had decreased to 0.0 mg/dL, but she developed multiple cutaneous leg ulcers associated with RV. Because of her advanced age, we changed her RA treatment from tocilizumab to the JAK inhibitor peficitinib in monotherapy, after which the ulcers improved within 6 months. This is the first report to indicate that peficitinib is a potential treatment option for RV that can be used in monotherapy without glucocorticoids or other immunosuppressants.

01 Oct 2023·International immunopharmacology

Peficitinib ameliorates 5-fluorouracil-induced intestinal damage by inhibiting aging, inflammatory factors and oxidative stress.

Article

Author: Dai, Qianlong ; Chen, Cui ; Wang, Xiao Bo ; Xia, Jing ; Jia, Huijie ; Zhou, Yue ; He, Siyue

5-Fluorouracil (5-FU) is a conventional and effective drug for colorectal cancer patients, and it is an important part of combined chemotherapy and adjuvant chemotherapy. Chemotherapy intestinal mucositis (CIM) is a severe side effect caused by 5-FU that, induces cancer treatment failure and affects patients' quality of life. The mechanism of 5-FU-induced CIM is related to normal cell senescence induced by 5-FU. Peficitinib, a Janus Kinase (JAK) inhibitor, treats inflammatory disorders, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, the therapeutic role and underlying mechanism of peficitinib in CIM remain unclear. The main objective of our research was to investigate the effects of peficitinib on 5-FU-induced senescence and intestinal damage in human umbilical vein endothelial (HUVEC) cells, human intestinal epithelial (HIEC) cells and BABL/C mice. The results showed that 5-FU caused intestinal damage by inducing aging and increasing inflammation and oxidative stress. Peficitinib alleviated aging by reducing senescence-beta-galactosidase (SA-β-gal) activity and the protein levels of aging indicators (p53, p21, p16). Moreover, peficitinib reversed the changes in senescence-associated secretory phenotype (SASP) expression caused by 5-FU. Besides, 5-FU induced release of inflammatory factors and oxidative stress indicators was reversed by peficitinib. Additionally, the combination of peficitinib and 5-FU reinforced the anticancer curative intent of 5-FU in two colorectal cancer cell lines (HCT116 cells and SW620 cells). In conclusion, peficitinib alleviates mucositis by alleviating aging, reducing inflammatory accumulation and oxidative stress and enhancing the antitumor activity of 5-FU.

2

News (Medical) associated with Peficitinib Hydrobromide

21 Sep 2023

·www.pharmaceutical-technology.com

EC grants approval for Menarini’s breast cancer therapy

The EC’s decision comes after the EMA’s Committee for Medicinal Products for Human Use provided a positive opinion recommending approval for Orserdu. Credit: ORION PRODUCTION/Shutterstock.com. The European Commission (EC) has granted approval for the Menarini Group’s Orserdu (elacestrant) to treat patients with estrogen receptor (ER)‑positive , HER2-negative, locally advanced or metastatic breast cancer (mBC). Orserdu received the approval as a monotherapy for usage in postmenopausal women and men with tumours carrying an activating ESR1 mutation. Recommended Reports Reports LOA and PTSR Model - Camrelizumab in Breast Cancer GlobalData Reports LOA and PTSR Model - Enzalutamide in Breast Cancer GlobalData View all Companies Intelligence Astellas Pharma Inc Menarini Asia-Pacific Pte Ltd Menarini C H M P INC Soc Co Ltd View all These patients also should have progressed after treatment with a minimum of one line of endocrine therapy such as a CDK 4/6 inhibitor to be eligible to receive Orserdu. The EC’s decision comes after the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) provided a positive opinion in July 2023 recommending a grant of approval for the therapy. Based on findings from the Phase III EMERALD clinical trial, the EC granted approval for Orserdu in this indication. Trial data showed that treatment with elacestrant offered statistically significant progression-free survival (PFS) compared with standard-of-care treatment with an approved endocrine monotherapy of the investigator’s preference. In patients whose tumours had ESR1 mutations, elacestrant offered a median PFS of 3.8 months compared with 1.9 months following treatment with SOC. Elacestrant also cut down the disease progression or mortality risk by 45% versus SOC. The Menarini Group CEO Elcin Barker Ergun said: “We have long known that patients living with metastatic breast cancer need effective and tolerable options which treat their disease while enabling them to focus on the things that matter to them. “We are proud of delivering a new breast cancer treatment that offers efficacy in a once-daily pill and represents the first innovation in endocrine therapy in nearly two decades; we are also incredibly grateful for the support of the oncology researchers and all the patients who participated in the clinical studies that made today’s achievement possible.” Menarini Asia-Pacific recently signed a deal to license Astellas Pharma ’s Smyraf for rheumatoid arthritis treatment.

Phase 3Drug ApprovalLicense out/inClinical Result

13 Sep 2023

·www.prnewswire.com

Menarini Asia-Pacific Enters into an Exclusive Licensing Agreement with Astellas to Commercialize Smyraf® in Taiwan and select South-East Asian markets

SINGAPORE, Sept. 13, 2023 /PRNewswire/ -- Menarini Asia-Pacific has entered into a long-term exclusive licensing partnership with Astellas Pharma Inc. (Astellas) for the development, manufacturing and commercialization of the orally administered Janus kinase (JAK) inhibitor Smyraf® 50 mg and 100 mg Tablets (generic name: peficitinib hydrobromide) in Taiwan for the treatment of rheumatoid arthritis. Smyraf® has been approved in Taiwan and has patent protection for composition of matter until 2032. Subject to the terms of the agreement, Astellas will receive total payments of up to €5.5 million including upfront and milestone payments. In addition, Menarini will pay Astellas a high-single digit percentage royalties on net sales of Smyraf®. Menarini will have an option to extend the rights to select South-East Asian markets. Smyraf® was developed and is currently marketed in Japan by Astellas and is indicated for the treatment of rheumatoid arthritis (including prevention of structural joint damage) in patients who have an inadequate response to conventional therapies. Rheumatoid arthritis (RA) is a chronic autoimmune disorder that primarily affects the joints, causing inflammation, pain, and potential joint damage. With an estimated prevalence of 287.0 per 100,000 persons in Taiwan[1], rheumatoid arthritis is acknowledged as a significant health problem, and efforts are being made to enhance its diagnosis, treatment, and management amidst an ageing population in the region. "Menarini has a long history as the partner of choice for many biopharmaceutical companies across the Asia-Pacific region and we are excited that Astellas has trusted Menarini to promote and commercialize Smyraf®. Patients suffering from rheumatoid arthritis often need different options if the treatment target is not achieved. With proven efficacy and flexible dosing benefits, Smyraf® will play an important role in this regard," said Maurizio Luongo, Chief Executive Officer of Menarini Asia-Pacific. [1]{Global Burden of Disease Collaborative Network}. 2020. Global Burden of Disease Study 2019 (GBD 2019) Results. Seattle. USA. {Institute for Health Metrics and Evaluation (IHME)}. / About Menarini Asia-Pacific Menarini Asia-Pacific is a member of the Menarini Group, the world's largest Italian biopharmaceutical company with a heritage of over 130 years and over 17,000 employees in more than 140 countries. Here in Asia-Pacific, Menarini's vision is to be a leading provider of important healthcare brands to improve the lives of people in the region. Menarini Asia-Pacific operates across the entire commercial value chain, from clinical development, regulatory approval, and product launch to lifecycle management with a diverse portfolio of proprietary and partnered brands in key therapeutic fields, including Consumer Health, Dermatology, Allergy/Respiratory, Gastroenterology, Cardio-metabolic, Anti-infectives, Oncology/Specialty Care and Men's Health. For the Financial Year 2022, the Menarini Group's revenue registered 4.15 billion euros, of which the Asia Pacific region has grown to become a dynamic engine of growth for the Group with more than 10% revenue contribution. For more information, visit Logo - SOURCE Menarini Asia-Pacific

License out/inDrug Approval

100 Deals associated with Peficitinib Hydrobromide

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External Link

KEGG	Wiki	ATC	Drug Bank
D10721	-	M01C	DB11708

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Rheumatoid Arthritis	JP	Astellas Pharma, Inc.	26 Mar 2019

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Plaque psoriasis	Phase 2	US	Astellas Pharma, Inc.	23 Mar 2010
liver function failure	Phase 1	JP	Astellas Pharma, Inc.	28 Dec 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04143477 (Pubmed \| Drug Des Devel Ther)	Phase 1	-	36	Peficitinib 50 mg	evowdghtio(ahsungddxo) = Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death. yuqivzloxi (cnqoeocwiw )	-	01 Jan 2022
				Peficitinib 100 mg
NCT01638013 (Pubmed \| Rheumatol Ther)	Phase 3	Rheumatoid Arthritis	843	Peficitinib 50 mg/day	pfhwmjewkx(bqsvotgllr) = lwxoswinmr xgvkmfmqkc (isghskyunl ) View more	-	03 Mar 2021
				Peficitinib 100 mg/day	pfhwmjewkx(bqsvotgllr) = eggtprnrgt xgvkmfmqkc (isghskyunl ) View more
ACR2020	Not Applicable	Rheumatoid Arthritis	-	Peficitinib	bsssxnqcup(yerrtcvygr) = cmjdkfqioj qqshxwyxyi (qszrefskdq, 1) View more	-	07 Nov 2020
NCT01638013 (CTgov)	Phase 3	Rheumatoid Arthritis	843	Peficitinib (Participants Who Completed 015K-CL-RAJ1)	eixrroskaj(lwcbergdke) = omypppzkrw gxjbgwlfrd (ebtolhesmc, iymmbvtyst - magnxcuena) View more	-	23 Oct 2020
				Peficitinib (Participants Who Completed 015K-CL-RAJ3)	eixrroskaj(lwcbergdke) = stcadjhekl gxjbgwlfrd (ebtolhesmc, bjtokhwvrb - raegrslkra) View more
NCT01638013 (Pubmed \| J Rheumatol) Manual	Phase 3	Rheumatoid Arthritis	843	peficitinib	wogwddhwjm(knmdrbrsje) = hhkahlzwkl xauvvnbrzf (iipviwjkfx ) View more	Positive	12 Mar 2020
NCT01711814 (Pubmed \| Rheumatol Ther) Manual	Phase 2	Rheumatoid Arthritis	611	Peficitinib	iekkmwpzqn(iyizntsuux) = zvnqdzzkkp xdxmsmnyhj (krufrsbkjx ) View more	Positive	01 Dec 2019
NCT02308163 (RAJ3, Pubmed \| Arthritis Rheumatol)	Phase 3	Rheumatoid Arthritis	507	Peficitinib 100 mg once daily	bfxkwzfqym(ecnfkcigwk) = hwhqwchvfi tdieteoiya (bdpdmfbhkw )	Positive	01 Oct 2019
				Peficitinib 150 mg once daily	bfxkwzfqym(ecnfkcigwk) = ncvjdszqsg tdieteoiya (bdpdmfbhkw )
NCT02305849 (RAJ4, Pubmed \| Arthritis Rheumatol)	Phase 3	Rheumatoid Arthritis	519	Placebo	ypgxcpycsn(zymnrlbygc) = wldthzweqy heidiarfmf (zitmustxsb )	Positive	01 Oct 2019
				Peficitinib 100 mg	ypgxcpycsn(zymnrlbygc) = xcldscftmv heidiarfmf (zitmustxsb )
NCT01565655 (Pubmed \| Arthritis Rheumatol)	Phase 2	Rheumatoid Arthritis	289	Peficitinib 25 mg	rjlcocsogb(uwvzttpgpi) = osvatpxmij cikehadvvf (kthoctfewj )	-	01 May 2017
				Peficitinib 50 mg	rjlcocsogb(uwvzttpgpi) = olefohscnp cikehadvvf (kthoctfewj )
NCT01554696 (Pubmed \| Arthritis Rheumatol)	Phase 2	Rheumatoid Arthritis	378	Peficitinib 25 mg	cfsfysuukv(ktdukwanym) = jkowjqwzia ddjcaosthb (hhbnvlgjzx )	Positive	01 Apr 2017
				Peficitinib 50 mg	cfsfysuukv(ktdukwanym) = chyxfvipzw ddjcaosthb (hhbnvlgjzx )