Delving into the Latest Updates on Bexarotene with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoic acid, 4-[1-(5,6,7,8,-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl)ethenyl]benzoic acid, Bexarotene (JAN/USAN/INN)

+ [20]

Target

RXRs

Mechanism

RXRs agonists(Retinoid X receptor agonists), Protein synthesis inhibitors

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [2]

Active Indication

Cutaneous T-Cell LymphomaCushing Syndrome

Inactive Indication

Advanced breast cancerAdvanced Lung AdenocarcinomaAdvanced Lung Non-Small Cell Carcinoma+ [6]

Originator Organization

Ligand Pharmaceuticals, Inc.

Active Organization

Eisai GmbHBausch Health Ireland Ltd.

Minophagen Pharmaceutical Co. Ltd.

+ [2]

Inactive Organization

Ligand Pharmaceuticals, Inc.

Eisai, Inc.

Drug Highest PhaseApproved

First Approval Date

US (29 Dec 1999),

Cutaneous T-Cell Lymphoma

RegulationOrphan Drug (US), Orphan Drug (JP)

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Structure

Molecular FormulaC24H28O2

InChIKeyNAVMQTYZDKMPEU-UHFFFAOYSA-N

CAS Registry153559-49-0

The researchers are doing this study to test the safety of combining bexarotene with TSEB radiotherapy in people who have a common form of CTCL called mycosis fungoides (MF).
Bexarotene is a form of vitamin A that activates proteins called retinoid X receptors, which may stop the growth of cancer cells and kill them. TSEB radiotherapy is a type of radiation therapy that treats the entire surface of the skin with very low doses of radiation to kill cancer cells and shrink tumors. This type of radiation does not pass through the outer layers of the skin into the tissues and organs below the skin.
The study researchers think that giving bexarotene treatment at the same time as treatment with TSEB radiotherapy may be more effective against MF than either treatment given alone or in sequence (one after the other).

Start Date16 Mar 2022

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

NCT04664829 / RecruitingPhase 1

Metastatic Triple-Negative Taxane-Resistant Breast Cancer: Investigating the Role of Bexarotene in Inducing Susceptibility to Chemotherapy by Differentiating Cancer Cells From a Mesenchymal-Like to an Epithelial-Like Phenotype

Triple-negative breast cancer (TNBC) is biologically aggressive and has limited systemic treatment options, often compounded by treatment resistance.
Cell state transitions, e.g. epithelial-to-mesenchymal transition (EMT) govern cancer cell behaviour.
The investigators hypothesize that by inducing change in cell state change, TNBC cells that have manifested taxane-resistance will be more sensitized to subsequent chemotherapy.

Start Date01 Oct 2020

Sponsor / Collaborator

National Cancer Centre of Singapore Pte Ltd.

ACTRN12620000825954 / CompletedPhase 1

A single dose, randomized, blinded, pharmacokinetic study of a generic formulation of 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule in a 2 way crossover comparison against the innovator 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule conducted under fed conditions in healthy volunteers.

Start Date21 Aug 2020

Sponsor / Collaborator

Zenith Technology Corp. Ltd.

100 Clinical Results associated with Bexarotene

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100 Translational Medicine associated with Bexarotene

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100 Patents (Medical) associated with Bexarotene

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1,008

Literatures (Medical) associated with Bexarotene

01 Mar 2024·Biochemistry and biophysics reports

A common molecular and cellular pathway in developing Alzheimer and cancer

Review

Author: Dey, Tathagata ; Wani, Shahid Ud Din ; Ali, Mohammad ; Qadrie, Zulfkar Latief ; Sridhar, Sathvik B

Globally cancer and Alzheimer's disease (AD) are two major diseases and still, there is no clearly defined molecular mechanism. There is an opposite relation between cancer and AD which are the proportion of emerging cancer was importantly slower in AD patients, whereas slow emerging AD in patients with cancer. In cancer, regulation of cell mechanisms is interrupted by an increase in cell survival and proliferation, while on the contrary, AD is related to augmented neuronal death, that may be either produced by or associated with amyloid-β (Aβ) and tau deposition. Stated that the probability that disruption of mechanisms takes part in the regulation of cell survival/death and might be implicated in both diseases. The mechanism of actions such as DNA-methylation, genetic polymorphisms, or another mechanism of actions that induce alteration in the action of drugs with significant roles in resolving the finding to repair and live or die might take part in the pathogenesis of these two ailments. The functions of miRNA, p53, Pin1, the Wnt signaling pathway, PI3 KINASE/Akt/mTOR signaling pathway GRK2 signaling pathway, and the pathophysiological role of oxidative stress are presented in this review as potential candidates which hypothetically describe inverse relations between cancer and AD. Innovative materials almost mutual mechanisms in the aetiology of cancer and AD advocates novel treatment approaches. Among these treatment strategies, the most promising use treatment such as tyrosine kinase inhibitor, nilotinib, protein kinase C, and bexarotene.

01 Feb 2024·Clinical lymphoma, myeloma & leukemia

Real-World Treatment Patterns and Clinical Outcomes With Brentuximab Vedotin or Other Standard Therapies in Patients With Previously Treated Cutaneous T-Cell Lymphoma in the United States

Article

Author: Liu, Nicholas ; Barta, Stefan K ; Surinach, Andy ; Duh, Mei Sheng ; Ye, Mingchen ; DerSarkissian, Maral ; Fanale, Michelle ; Yu, Kristina S ; Chang, Rose

INTRODUCTION/BACKGROUND:

Primary cutaneous anaplastic large-cell lymphomas (pcALCLs) are a type of cutaneous T-cell lymphoma (CTCL) in which CD30 is uniformly expressed. In mycosis fungoides (MF), another CTCL, CD30 is heterogeneously expressed. In ALCANZA, patients with pcALCLs or CD30-positive MF randomized to brentuximab vedotin (BV) vs. physician's choice of methotrexate or bexarotene had significantly improved outcomes, including higher objective response rates (ORR) lasting ≥4 months (ORR4), as well as longer median progression-free survival (PFS) and time to next treatment (TTNT). In this study, we sought to assess the real-world impact of treatment with BV in second or later lines of therapy for CTCL.

MATERIALS AND METHODS:

This retrospective chart review describes patient characteristics, treatment patterns, clinical outcomes, and healthcare resource use (HRU) in patients with pcALCLs or MF previously treated with ≥1 systemic therapy and subsequently treated with BV (n = 139) or other standard therapy (OST; n = 164).

RESULTS:

Most patients in the BV cohort (96.4%) received BV as second-line (2L) systemic therapy. The most common OSTs were methotrexate (11.6%), mogamulizumab (9.1%), and bendamustine (9.1%) monotherapies. For 2L BV and OST, median duration of therapy was 8.4 and 5.2 months, real-world ORR was 82.1% and 66.5%, and real-world ORR4 was 42.5% and 25.0%. Real-world 1- and 2-year PFS, TTNT, and OS were significantly longer (all P < .01) and HRU was lower for BV vs. OST.

CONCLUSION:

These real-world outcomes are consistent with ALCANZA results, demonstrating favorable outcomes with BV vs. OST in patients with CTCL previously treated with ≥1 systemic therapy.

01 Jan 2024·Hematological oncology

Possible effects of plasminogen activator inhibitor‐1 on promoting angiogenesis through matrix metalloproteinase 9 in advanced mycosis fungoides

Article

Author: Fujimura, Taku ; Kambayashi, Yumi ; Furudate, Sadanori ; Ohuchi, Kentaro ; Asano, Yoshihide ; Ikawa, Tetsuya ; Amagai, Ryo

Abstract:

Mycosis fungoides (MF) progresses slowly before advancing to skin tumors followed by lymph node and visceral involvement. Among MF progression, stage IIB is an initial time point of tumor formation in MF. Since MF in tumor stage possess abundant blood vessels, it is important to evaluate the pro‐angiogenic factors before and after MF in stage IIB. In this report, we investigated pro‐angiogenic soluble factors in MF patients, as well as its pro‐angiogenetic effects on tumor cells and stroma cells. We first evaluated the serum levels of pro‐angiogenic factors in 9 MF patients without tumor formation and 8 MF patients with tumor formation. Among them, the serum MMP‐9 and plasminogen activator inhibitors 1 (PAI‐1) was significantly increased in MF with tumor formation compared in MF without tumor formation, leading to favorable formation of human dermal microvascular endothelial cells tube networks. Moreover, PAI‐1 stimulation significantly increased the mRNA expression and protein production MMP‐9 on monocytes derived M2 macrophages and HUT‐78. Furthermore, since MMP‐9 production from tumor cells as well as stromal cells is suppressed by bexarotene, we evaluate the baseline serum pro‐angiogenic factors including MMP‐9 in 16 patients with advanced cutaneous T cell lymphoma treated with bexarotene. The serum levels of MMP‐2 and MMP‐9 was significantly increased in bexarotene non‐responded patients compared to responded patients. Our present study suggested the significance of MMP‐9 and PAI‐1 for the progression of MF stage toward to the tumor stage, and could be a therapeutic target in future.

2

News (Medical) associated with Bexarotene

26 Oct 2023

·www.prnewswire.com

SciTech Development Announces The Formation of a Distinguished Medical Advisory Board With Top Oncology Specialists

GROSSE POINTE FARMS, Mich., Oct. 26, 2023 /PRNewswire/ -- SciTech Development, LLC, today announced the formation of a distinguished and independent medical advisory board (MAB) comprised of key opinion leaders and world-renowned experts in T-Cell Lymphomas and hematological malignancies. The board will provide strategic and clinical advice for SciTech's outreach and education initiatives within the oncology community. Continue Reading SciTech Medical Advisory Board "SciTech is excited and incredibly proud that this world-class group of medical experts will assist us with innovative insights that enable us to bring ST-001 to patients who have limited options in their cancer treatments," said President and Managing Partner Earle Holsapple. "The clarity they bring in understanding the clinical needs of patients will serve to guide us through the commencement of our phase 1 clinical trial and through our subsequent expedited clinical program." The three medical advisors appointed to the board are Madeleine Duvic, M.D., Larisa Geskin, M.D., and Ajay Gopal, M.D. Madeleine Duvic, MD – "The development of ST-100 is exciting because this new drug holds the promise of improved bioavailability, leading to increased efficacy with low toxicity." Dr. Duvic is a Professor of Medicine and Dermatology practices in Houston, Texas, and holds the Blanche Bender Endowed Chair of Research. Her clinical research includes translational/molecular studies leading to improved therapies for cutaneous T-cell lymphomas. She has written over 500 peer-reviewed papers and a book on Retinoids. She participated in the development of topical and oral tazarotene and bexarotene which both received FDA approval. Larisa J. Geskin, MD, FAAD - "I am thrilled to support SciTech's innovative approach to cancer therapeutics. SciTech's patented nanoparticle platform, SDP, enhances the effectiveness and safety of fenretinide, which has shown promise in treating patients with incurable cutaneous lymphomas in preliminary studies. SciTech's flagship product, ST-001, stands out for its ability to deliver therapeutic doses without toxic side effects, greatly benefiting our patients." Dr. Geskin is a Professor of Dermatology (in Medicine, Division of Hematology-Oncology) at Columbia University Medical Center and the Director of the Comprehensive Cutaneous Oncology Center at the Columbia University Department of Dermatology. Dr. Geskin serves as the Immediate Past-President of the International Society for Cutaneous Lymphomas (ISCL), the Secretary-Treasurer of the US Cutaneous Lymphomas Consortium (USCLC), and the Founding Chair of the New York Cutaneous Lymphoma Consortium (NYCLC), among her many other responsibilities. Ajay K. Gopal, MD - "Based on the encouraging preclinical data from a variety of laboratories, our observed tolerability of fenretinide, and the unmet need in a spectrum of malignancies novel formulations such as ST-001 nanoFenretinide are certainly worthy of further investigation." Dr. Gopal received his undergraduate degree from Duke University and his MD from Emory University. He completed his internal medicine training at Duke University School of Medicine and his oncology training at the University of Washington and Fred Hutchinson Cancer Center, where he currently holds an endowed chair and serves as a Professor and Clinical Research Director for Hematologic Malignancies. Dr. Gopal has over 2 decades of experience in the development of novel therapies for lymphoma, as reflected by over 200 publications in the field, including the first translational and clinical trial data evaluating fenretinide in lymphoma. Contact: Earle Holsapple Email: [email protected] About SciTech Development SciTech Development, LLC is a clinical-stage pharmaceutical company that has developed a patented nanoparticle drug delivery platform (SDP) that maximizes the bioavailability of water-insoluble therapeutics. SciTech's lead drug candidate, ST-001 nanoFenretinide, combines SDP and the drug fenretinide as a new drug product with potentially broad effectiveness in many cancers. For more information about the Company, please visit: SOURCE SciTech Development

Phase 1Executive Change

17 Nov 2022

·medcitynews.com

Two Pharmacy Owners Plead Guilty in $18M Foreign Medicare Fraud Scheme

Two New York pharmacy owners who “exploited the Covid-19 emergency for their own financial gain,” pleaded guilty to an international scheme to submit fraudulent claims to Medicare for cancer medication, the Department of Justice announced Wednesday. Arkadiy Khaimov, 39, of Forest Hills, and Peter Khaim, 42, also of Forest Hills, engaged in an elaborate healthcare scheme involving more than a dozen pharmacies in New York, according to the justice department. The two would submit millions of dollars in fraudulent Medicare claims for expensive cancer drugs that were not prescribed or distributed to patients. The drugs, Targretin gel, made by Bausch and Panretin gel, made by Concordia, were allegedly dispensed during periods when certain pharmacies were closed due to the pandemic. “Khaim, Khaimov, and their co-conspirators exploited the Covid-19 emergency for their own financial gain by using COVID-19-related ‘emergency override’ billing codes to submit additional fraudulent claims for Targretin Gel 1%,” the justice department said in a news release. The scheme started in New York but became a complex international endeavor as the two men attempted to launder money, amounting to more than $18 million. Khaim and Khaimov established shell companies and sham pharmacy wholesale companies to create the illusion they were operating actual businesses. In reality, they were sending funds from the false Medicare claims to the sham companies. Then, the funds were sent to companies in China and distributed to individuals in Uzbekistan. At that point, the two men received some of the funds in cash, the announcement said. They also allegedly sent money from the fraudulent claims to their relatives through cashier’s checks and used the money themselves to purchase property. Both men face a 20-year prison sentence and their separate hearings are scheduled for May 2023. A spokeperson for the Center for Medicare and Medicaid Services did not immediately respond to a request for comment.

Patent Infringement

100 Deals associated with Bexarotene

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External Link

KEGG	Wiki	ATC	Drug Bank
D03106	Bexarotene	L01XX25	DB00307

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cutaneous T-Cell Lymphoma	US	Valeant Pharmaceuticals Luxembourg SARL	29 Dec 1999

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alopecia Areata	Phase 3	US	Ligand Pharmaceuticals, Inc.	01 May 2003
metastatic non-small cell lung cancer	Phase 3	US	Eisai, Inc.	01 May 2002
metastatic non-small cell lung cancer	Phase 3	AT	Eisai, Inc.	01 May 2002
metastatic non-small cell lung cancer	Phase 3	CA	Eisai, Inc.	01 May 2002
metastatic non-small cell lung cancer	Phase 3	FR	Eisai, Inc.	01 May 2002
metastatic non-small cell lung cancer	Phase 3	DE	Eisai, Inc.	01 May 2002
metastatic non-small cell lung cancer	Phase 3	ES	Eisai, Inc.	01 May 2002
Psoriasis vulgaris	Phase 2	-	Ligand Pharmaceuticals, Inc.	01 Nov 2003
AIDS-related Kaposi Sarcoma	Phase 2	US	Ligand Pharmaceuticals, Inc.	31 Aug 2001
Advanced Lung Adenocarcinoma	Phase 2	US	Ligand Pharmaceuticals, Inc.	01 Aug 2001

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03323658 (CTgov)	Phase 1	Atypical Lobular Breast Hyperplasia \| Noninfiltrating Intraductal Carcinoma \| Invasive Mammary Carcinoma	24	Bexarotene (Dose Level 1)	acnowmylfy(wrvrwmwlqh) = afmqvcyifs fxenraxayw (aeblqnocsm, pjcihwldtr - inhtkprbht) View more	-	06 Dec 2022
NCT03323658 (CTgov)	Phase 1		24	Bexarotene (Dose Level 2)	acnowmylfy(wrvrwmwlqh) = kmmrltkyoz fxenraxayw (aeblqnocsm, hsbjtolsiy - fgaxnnfdom) View more	-	06 Dec 2022
ISRCTN14265371 (CCMR One, ECTRIMS2021)	Phase 2	-	31	Bexarotene	ksbbyhsmkd(ubdznadbgv) = significant adverse events were observed on the trial ebbucdnrms (agqwztcnqq )	Positive	12 Oct 2021
NCT00615784 (CTgov)	Phase 2	Acute Myeloid Leukemia	24	Bexarotene	dwrbqeogxb(tadrtvzvcy) = fsxopcopgz snawasmpnn (iabdrifqjk, exnhpzhono - vskjxecuej) View more	-	17 Nov 2020
NCT01007448 (CTgov)	Phase 4	CD30-Positive recurrent or refractory Cutaneous T-Cell Lymphoma	59	Bexarotene	rgwcmqtahv(zlqixyqqsp) = qyhkgkyczq mccabdpaqt (duzmwyydve, ashxiewlaf - aievrswdww) View more	-	12 Nov 2019
NCT00125372 (CTgov)	Not Applicable	stage IIA non-small cell lung cancer	12	Tarceva+Targretin	ecdkwebpeu(etrnhqsujn) = vmoizasfab tpmhqqgulz (jqyrbaiuup, bbqknubtee - pvmtyejfpu) View more	-	13 Nov 2018
NCT00125359 (CTgov)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	42	Erlotinib+Bexarotene	okmcglgzgl(ieykgjfsvm) = zifrpqlxwl ddwtgkfpuu (jnfrxktjjo, clzqnywsxe - lmjklhxcmw) View more	-	13 Nov 2018
NCT00425477 (CTgov)	Phase 2	Acute Myeloid Leukemia \| Myelodysplastic-Myeloproliferative Diseases \| Myelodysplastic Syndromes	26	flow cytometry+Bexarotene+sargramostim	qpihkqpsrx(uxnwpckcrl) = tmkyxsghao numorprytv (dkkldzjaub, bomvrbpzov - wovmomwtea) View more	-	05 Sep 2018
EHA2017	Not Applicable	Mycosis Fungoides \| Sezary Syndrome	21	Bexarotene and PUVA in combination	tzgdkaqeqs(saefhbqrdd) = hgadhiuvkr ftrevvkltc (iiuupwutqz ) View more	-	18 May 2017
NCT01782742 (CTgov)	Phase 2	Alzheimer Disease	20	Placebo (Placebo)	plndubvzfr(oyzhyewhro) = nqaerwupbw yvzapaedxl (agsabbgflo, fclyndjfsu - lulnevdnqr) View more	-	12 Feb 2016
NCT01782742 (CTgov)	Phase 2	Alzheimer Disease	20	Bexarotene (Bexarotene Treatment Arm)	xqbgnljzrv(olgasfwpdx) = dftpsixeum bzrvsslsqw (ntmpijspsx, vuxdvtorvj - blvfoxdjvn) View more	-	12 Feb 2016
NCT00718770 (CTgov)	Early Phase 1	thyroid gland poorly differentiated carcinoma	10	Bexarotene	ehyqrqxqcj(bshqhdubbd) = eenlodnbxo uxlthirgow (wbmxeqlsnq, zvxllbyrxq - nfujmqhzjx) View more	-	17 Jan 2014