A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy as Well as in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis (NASH)

This is a Phase 2a Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy as well as in Combination with TERN-101 in Noncirrhotic Adults with Presumed Non-Alcoholic Steatohepatitis (NASH)

Start Date07 Jul 2022

Sponsor / Collaborator

Terns, Inc.

NCT04328077 / CompletedPhase 2

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2a Clinical Trial to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Orally Administered TERN-101 Tablets in Adult Patients With Presumed Non-Cirrhotic Non-Alcoholic Steatohepatitis (NASH)

This is a Phase 2, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of TERN-101 in non-cirrhotic NASH patients.

Start Date18 Jun 2020

Sponsor / Collaborator

Terns, Inc.

NL-OMON32962 / CompletedNot Applicable

A MULTIPLE ASCENDING DOSE PHARMACOLOGY, FOOD EFFECT AND DRUG INTERACTION STUDY OF LY2562175 IN HEALTHY ADULT SUBJECTS - LY2562175 MAD/DDI/FE study

Start Date06 Aug 2009

Sponsor / Collaborator-

100 Clinical Results associated with LY-2562175

100 Translational Medicine associated with LY-2562175

100 Patents (Medical) associated with LY-2562175

Literatures (Medical) associated with LY-2562175

02 Jun 2020·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH)

Q2 · MEDICINE

Review

Author: Biagioli, Michele ; Zampella, Angela ; Sepe, Valentina ; Distrutti, Eleonora ; Fiorucci, Stefano

INTRODUCTIONNonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) for which therapy is suboptimal. The farnesoid-X-receptor (FXR) and the G protein bile acid receptor (GPBAR)1 are two bile acid-activated receptors that exert regulatory effects on lipid, glucose, energy, and immune homeostasis. GPBAR1 and FXR ligands have shown efficacy in reversing steatohepatitis and fibrosis in preclinical models of NASH.AREA COVEREDThis article evaluates the efficacy and pitfalls of GPBAR1 and FXR-based therapies in the treatment of NASH. While there are no GPBAR1 agonist in clinical development, several FXR ligands have completed phase 2 and phase 3 trials in NASH. EDP305, tropifexor, cilofexor, nidufexor, TERN.101, Px-104, EYP001, MET409. Individual FXR agonists have shown variable efficacy in reversing liver steatohepatitis and fibrosis. Class-related, dose-dependent side effects: pruritus, increased plasma levels of cholesterol and LDLc, and reduction of HDL have been reported.EXPERT OPINIONEfficacy of FXR agonists as stand-alone therapy is limited by dose-related side effects. Efficacy of combining an FXR agonist with statins, CCR2, and ACC inhibitors is currently investigated. Identification of patient subsets would allow development of patients tailored therapy using a combination of drugs acting on different molecular mechanisms.

24 Dec 2015·Journal of Medicinal ChemistryQ1 · MEDICINE

Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia

Q1 · MEDICINE

Article

Author: Stille, John R. ; Jones, Timothy M. ; Bocchinfuso, Wayne P. ; Raddad, Eyas ; Agejas Francisco, Javier ; Manninen, Peter R. ; Bueno, Ana B. ; Reidy, Charles ; Montrose-Rafizadeh, Chahrzad ; Genin, Michael J. ; Michael, Laura F. ; Cox, Amy ; Cannady, Ellen A. ; Michael, M. Dodson

The farnesoid X receptor (FXR) is a member of the "metabolic" subfamily of nuclear receptors. Several FXR agonists have been reported in the literature to have profound effects on plasma lipids in animal models. To discover novel and effective therapies for dyslipidemia and atherosclerosis, we have developed a series of potent FXR agonists that robustly lower plasma LDL and vLDL in LDLr-/- mice. To this end the novel piperidinylisoxazole system LY2562175 was discovered. This molecule is a potent and selective FXR agonist in vitro and has robust lipid modulating properties, lowering LDL and triglycerides while raising HDL in preclinical species. The preclinical ADME properties of LY2562175 were consistent with enabling once daily dosing in humans, and it was ultimately advanced to the clinic for evaluation in humans. The synthesis and biological profile of this molecule is discussed.

111

News (Medical) associated with LY-2562175

13 Nov 2024

·www.globenewswire.com

Organovo to Present Clinical Data of FXR314 in Phase 2 MASH in an Oral Presentation at The Liver Meeting Sponsored by the American Association for the Study of Liver Diseases

SAN DIEGO, Nov. 13, 2024 (GLOBE NEWSWIRE) -- Organovo Holdings, Inc. (Nasdaq:ONVO), a clinical stage biotechnology company focused on developing novel treatment approaches in inflammatory bowel disease (IBD) including ulcerative colitis, today announces that its lead clinical stage drug, FXR314 will be featured in an oral presentation at The Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD). The presentation, by Dr. Eric Lawitz of the Texas Liver Institute, will describe the findings from the FXR314 Phase 2 MASH study. The meeting will be held November 15-19, 2024 in San Diego, California. Details include: PresenterDr Eric Lawitz, Texas Liver InstituteSession Date / Time:11/17/2024, 2:00 pm - 3:30 pm PSTSession Title:MASLD and MASH - New Therapies Type:Abstract ParallelPresentation Title:PHARMACOKINETICS, SAFETY AND EFFICACY OF THE NOVEL NON-BILE ACID FXR AGONIST FXR314 IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS: RESULTS FROM A PHASE 2 STUDY Presentation Time:3:00 pm - 3:15 pm PST About OrganovoOrganovo is a clinical stage biotechnology company that is developing drugs that are demonstrated to be effective in three-dimensional (3D) human tissues as candidates for drug development. The company’s lead molecule, FXR314, is on the path for Phase 2 investigation in inflammatory bowel disease and has potential application in metabolic liver disease and oncology. The company has proprietary technology used to build 3D human tissues that mimic key aspects of native human tissue composition, architecture, function, and disease. For more information visit Organovo's website at www.organovo.com. Forward Looking StatementsAny statements contained in this press release that do not describe historical facts constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations but are subject to a number of risks and uncertainties. These risks and uncertainties and other factors are identified and described in more detail in the Company’s filings with the SEC, including its Annual Report on Form 10-K filed with the SEC on May 31, 2024, as such risk factors are updated in its most recently filed Quarterly Report on Form 10-Q filed with the SEC on November 8, 2024 and the Registration Statement on Form S-1 (File No. 333-282841). You should not place undue reliance on these forward-looking statements, which speak only as of the date that they were made. These cautionary statements should be considered with any written or oral forward-looking statements that the Company may issue in the future. Except as required by applicable law, including the securities laws of the United States, the Company does not intend to update any of the forward-looking statements to conform these statements to reflect actual results, later events, or circumstances or to reflect the occurrence of unanticipated events. ContactCORE IRpr@coreir.com Source: Organovo, Inc.

Phase 2Clinical Result

12 Nov 2024

·firstwordpharma.com

Intercept's Ocaliva denied full approval for PBC, but it gets to stay on the market — for now

In line with an earlier FDA advisory committee (adcom) vote, the US regulator on Tuesday rejected Intercept Pharmaceuticals' filing for full approval of Ocaliva (obeticholic acid) to treat primary biliary cholangitis (PBC). The FXR agonist will continue to be available to patients under its accelerated approval status, granted in 2016, but the FDA is continuing to review safety data for the drug that may result in its removal from the market. Such a decision would align with other regional regulators, as the European Commission revoked the Ocaliva's conditional marketing authorisation in September, though the move has since been temporarily suspended by the General Court of the European Union.The US agency first shared concerns about the drug's clinical benefit and safety profile in briefing documents released ahead of the adcom meeting. FDA staffers pointed to Ocaliva's 747-302 post-marketing trial, which failed on the expanded primary composite endpoint of preventing liver transplantation, death or other liver-related issues in patients with chronic PBC. The data also revealed "unfavourable trends" with the drug regarding liver transplants and survival rates in both the intent-to-treat population and those labelled under its current use guidelines.The committee panellists seemed to share those concerns, voting 13-1 that the available evidence does not support Ocaliva's clinical benefit in patients with PBC, and 10-1 — with three abstentions — that the drug has an unfavourable benefit-risk profile.In Tuesday's complete response letter, which denied full approval for Ocaliva but did not revoke its accelerated approval, the FDA said it will continue to consider safety data from 747-302, along with other safety information."We believe in the totality of evidence supporting Ocaliva and intend to work closely with the FDA on next steps," said Vivek Devaraj, Intercept's president and chairman of US operations. "We remain committed to patients living with PBC who have limited treatment options."The company was acquired by Alfasigma last year for nearly $800 million.

Accelerated ApprovalAcquisitionDrug Approval

17 Oct 2024

·endpts.com

Intercept's liver disease drug faces full approval delay following negative adcomm

Following a nearly unanimous adcomm against Alfasigma and Intercept Pharmaceuticals’ rare liver disease drug Ocaliva, the FDA has delayed its decision on whether to convert the drug from an accelerated to a full approval. The original PDUFA date for the drug’s sNDA was Oct. 16. For now, the treatment remains available via the accelerated approval for patients with primary biliary cholangitis in the US, Intercept president Vivek Devaraj wrote in a statement , adding that the company “will continue to engage with the FDA regarding our pending application.” The treatment has faced multiple setbacks since its accelerated approval in 2016, including the addition of a boxed warning in 2018 after it was being incorrectly dosed as a daily treatment, as opposed to a weekly treatment. Alfasigma bought the drug as part of its $800 million buyout of Intercept Pharmaceuticals last year. The FDA adcomm in September recommended against full approval for the FXR agonist by a 13-1 vote, concluding that confirmatory trial data didn’t verify that the treatment provided a clinical benefit. The adcomm discussed data from two studies: a traditional confirmatory study designed to be randomized and placebo-controlled, and a real-world evidence trial. In a separate vote, panelists decided 10-1 that the benefits of Ocaliva did not outweigh its risks, with three abstentions. The European Commission also revoked Ocaliva’s conditional marketing authorization in September, which was available in Europe as a second-line treatment in the liver disease. The decision came after a June recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use, which reassessed the benefit-risk profile of the drug.

Accelerated ApprovalAcquisitionDrug Approval

100 Deals associated with LY-2562175

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nonalcoholic Steatohepatitis	Phase 2	US	Terns, Inc.	18 Jun 2020
Cholangitis	Phase 2	US	Terns Pharmaceuticals, Inc.	17 Jul 2019
Dyslipidemias	Phase 2	US	Eli Lilly & Co.	24 Dec 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05415722 (DUET, GlobeNewswire) Manual	Phase 2	Nonalcoholic Steatohepatitis	-	TERN-501	(qzqdnanjbd) = tyidfyzjdy wcyqedhcxl (aabveiaaes )	Positive	13 Nov 2023
				TERN-501	(qzqdnanjbd) = rkqgayyloe wcyqedhcxl (aabveiaaes )
NCT04328077 (LIFT, CTgov)	Phase 2	Nonalcoholic Steatohepatitis	101	Placebo	kjmqaoejsw(mlqrjvikoy) = mfamodjdpv awychtxtvt (djchhriels, plysoaiqlm - gpyztqrylt) View more	-	14 Jun 2022
NASH_TAG2021	Phase 2	7-alpha-hydroxy-4-cholesten-3-one \| FXR pathway genes	-	TERN-101 (10 mg/kg)	zvfbmocida(yongghcphj) = ukqgrvbajp hfshetzuhk (vwmipsiogl, p<0.01) View more	Positive	12 Mar 2021
				OCA (30 mg/kg)	zvfbmocida(yongghcphj) = uozrhorqzj hfshetzuhk (vwmipsiogl, p<0.05) View more

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