A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY IN HEALTHY ADULT MALE PARTICIPANTS TO ASSESS THE EXTENT OF EXCRETION, ABSOLUTE BIOAVAILABILITY, FRACTION ABSORBED, AND PHARMACOKINETICS OF [14C]PF-06865571 USING A 14C-MICROTRACER APPROACH

This study is a Phase 1, open-label, non-randomized, 2-period, fixed-sequence, single-dose study of PF-06865571 in healthy male participants to characterize the ADME properties of [14C]PF-06865571 following oral administration; and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-06865571 following oral administration of unlabeled PF-06865571 and IV administration of [14C]PF-06865571.

Start Date11 May 2021

Sponsor / Collaborator

Pfizer Inc.

NCT04839393

/ CompletedPhase 1

A PHASE 1, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETIC INTERACTIONS BETWEEN PF-06882961 AND PF-06865571 IN HEALTHY ADULT PARTICIPANTS (PART A) AND OVERWEIGHT ADULTS OR ADULTS WITH OBESITY WHO ARE OTHERWISE HEALTHY (PART B)

This study will be conducted in 2 parts. Part A will investigate the potential effect of PF-06865571 on the pharmacokinetics (PK) of PF-06882961 in healthy adult participants. Part B will evaluate the effect of PF-06882961 on the PK of PF-06865571, as well as the effect of PF-06865571 on the PK of PF-06882961 in overweight adults or adults with obesity who are otherwise healthy.

Start Date05 Apr 2021

Sponsor / Collaborator

Pfizer Inc.

NCT04399538

/ CompletedPhase 2

A PHASE 2A, 2-PART, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY PLACEBO-CONTROLLED, PARALLEL-GROUP (SPONSOR OPEN) STUDY TO ASSESS PHARMACODYNAMICS AND SAFETY OF PF-06865571 (DGAT2I) COADMINISTERED WITH PF-05221304 (ACCI) IN ADULT PARTICIPANTS WITH PRESUMED NONALCOHOLIC STEATOHEPATITIS (NASH)

The study will evaluate the effect of coadministration of a range of doses of DGAT2i with 1 dose of ACCi, on hepatic steatosis and the ability of DGAT2i to mitigate ACCi-induced elevations in serum triglycerides. The study has a 2-part design with sequential conduct of Part 1 and Part 2 with each part conducted in distinct/separate cohorts of participants. The overall study design, objectives/endpoints, eligibility criteria for both parts is envisioned to be identical, however, data from Part 1 will be used to determine whether to conduct Part 2.

Start Date10 Aug 2020

Sponsor / Collaborator

Pfizer Inc.

100 Clinical Results associated with Ervogastat

100 Translational Medicine associated with Ervogastat

100 Patents (Medical) associated with Ervogastat

Literatures (Medical) associated with Ervogastat

01 Oct 2025·Lancet Gastroenterology & Hepatology

Efficacy and safety of ervogastat alone and in combination with clesacostat in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis and F2–F3 fibrosis (MIRNA): results from a phase 2, randomised, double-blind, double-dummy study

Article

Author: Nakajima, Atsushi ; Takahashi, Hirokazu ; Charlton, Michael ; Alkhouri, Naim ; Darekar, Amanda ; Tacke, Frank ; Wong, Vincent Wai-Sun ; Anstee, Quentin M ; Amin, Neeta B ; Rodriguez, Hector ; Kiszko, Jan

BACKGROUND:

Ervogastat, a diacylglycerol acyltransferase 2 (DGAT2) inhibitor, and clesacostat, an acetyl-coenzyme A carboxylase (ACC) inhibitor, have shown promise in reducing hepatic steatosis. Increased circulating triglycerides, a mechanistic consequence of ACC inhibitors, has been shown to be downregulated by DGAT2 inhibitor co-administration. We assessed the efficacy and safety of ervogastat alone and ervogastat plus clesacostat in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3.

METHODS:

This phase 2 double-blind, double-dummy, randomised study was conducted at 198 clinical sites across 11 countries. A computer-generated randomisation code (random permuted blocks method) was used to allocate patients to treatment groups in equal ratios, and stratified based on degree of fibrosis (F2 vs F3), using an interactive response technology system to ervogastat (25 mg, 75 mg, 150 mg, or 300 mg), ervogastat plus clesacostat (150 mg plus 5 mg or 300 mg plus 10 mg), or placebo, twice daily for 48 weeks. The primary endpoint was the proportion of patients achieving MASH resolution without fibrosis worsening, at least 1 stage fibrosis improvement without MASH worsening, or both, at week 48. Patients were analysed according to the treatment group they were assigned to. The primary endpoint was analysed based on the full analysis set (all randomly assigned patients who took at least one dose of study treatment who provided evaluable baseline biopsy data) in which patients missing a week 48 biopsy were considered non-responders. This completed trial was registered with ClinicalTrials.gov (NCT04321031).

FINDINGS:

Recruitment began June 15, 2020; randomisation was completed Feb 22, 2023, with 255 patients randomly assigned and given treatment (73% of planned sample size; ervogastat 25 mg: N=35; ervogastat 75 mg: N=48; ervogastat 150 mg: N=42; ervogastat 300 mg: N=31; ervogastat 150 mg plus clesacostat 5 mg: N=35; ervogastat 300 mg plus clesacostat 10 mg: N=30; placebo: N=34). 13 (38%) patients in the placebo group achieved the composite primary endpoint, as did 16 (46%) in the ervogastat 25 mg group (difference from placebo in the proportion of patients achieving the primary endpoint 0·08 [90% CI -0·11 to 0·27]), 25 (52%) in the ervogastat 75 mg group (0·14 [-0·04 to 0·32]), 21 (50%) in the ervogastat 150 mg group (0·12 [-0·07 to 0·30]), and 14 (45%) in the ervogastat 300 mg group (0·07 [-0·12 to 0·27]). 23 (66%) patients in the ervogastat 150 mg plus clesacostat 5 mg group (difference from placebo 0·27 [90% CI 0·07 to 0·43]) and 19 (63%) of those in the ervogastat 300 mg plus clesacostat 10 mg group (0·25 [0·04 to 0·42]) achieved the composite primary endpoint. Thus, the primary endpoint was not met by any doses of ervogstat alone, but was met by both dose levels of ervogastat plus clesacostat. All experimental groups showed greater effects on MASH resolution without worsening of fibrosis than with placebo alone; improvement in fibrosis by one stage or more without worsening of MASH was not greater in any experimental group compared with placebo. Most adverse events were mild or moderate in severity and did not increase in frequency or severity with increasing dose; however, ervogastat plus clesacostat was associated with a likely undesirable fasting lipid and apolipoprotein profile. The most common adverse event was inadequate control of diabetes (placebo: 4/34 [12%]; ervogastat 25 mg: 6/35 [17%]; ervogastat 75 mg: 5/48 [10%]; ervogastat 150 mg: 3/42 [7%]; ervogastat 300 mg: 2/31 [6%]; ervogastat 150 mg plus clesacostat 5 mg: 2/35 [6%]; ervogastat 300 mg plus clesacostat 10 mg: 2/30 [7%]). There were no fatal events; 19/255 (7%) patients reported 20 serious adverse events (placebo: 1/34 [3%]; ervogastat 25 mg: 1/35 [3%]; ervogastat 75 mg: 5/48 [10%]; ervogastat 150 mg: 1/42 [2%]; ervogastat 300 mg: 4/31 [13%]; ervogastat 150 mg plus clesacostat 5 mg: 5/35 [14%]; ervogastat 300 mg plus clesacostat 10 mg: 2/30 [7%]).

INTERPRETATION:

The combined efficacy, safety, and tolerability data with ervogastat supports continued investigation for its use in MASH. Larger and longer trials are needed to further assess ervogastat and ervogastat plus clesacostat for MASH treatment.

FUNDING:

Pfizer.

01 Feb 2025·CPT-Pharmacometrics & Systems Pharmacology

Exposure–response modeling of liver fat imaging endpoints in non‐alcoholic fatty liver disease populations administered ervogastat alone and co‐administered with clesacostat

Article

Author: Wojciechowski, Jessica ; Hughes, Jim H. ; Vourvahis, Manoli ; Amin, Neeta B.

Abstract:

Non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis describe a collection of liver conditions characterized by the accumulation of liver fat. Despite biopsy being the reference standard for determining the severity of disease, non‐invasive measures such as magnetic resonance imaging proton density fat fraction (MRI‐PDFF) and FibroScan® controlled attenuation parameter (CAP™) can be used to understand longitudinal changes in steatosis. The aim of this work was to describe the exposure–response relationship of ervogastat with or without clesacostat on steatosis, through population pharmacokinetic/pharmacodynamic (PK/PD) modeling of both liver fat measurements simultaneously. Population pharmacokinetic and exposure–response models using individual predictions of average concentrations were used to describe ervogastat/clesacostat PKPD. Due to both liver fat endpoints being continuous‐bounded outcomes on different scales, a dynamic transform‐both‐sides approach was used to link a common latent factor representing liver fat to each endpoint. Simultaneous modeling of both MRI‐PDFF and CAP™ was successful with both measurements being adequately described by the model. The clinical trial simulation was able to adequately predict the results of a recent Phase 2 study, where subjects given ervogastat/clesacostat 300/10 mg BID for 6 weeks had a LS means and model‐predicted median (95% confidence intervals) percent change from baseline MRI‐PDFF of −45.8% and −45.6% (−61.6% to −31.8%), respectively. Simultaneous modeling of both MRI‐PDFF and CAP™ was successful with both measurements being adequately described. By describing the underlying changes of steatosis with a latent variable, this model may be extended to describe biopsy results from future studies.

01 Oct 2024·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Combined structure-based virtual screening and machine learning approach for the identification of potential dual inhibitors of ACC and DGAT2

Article

Author: Deng, Liangying ; Zhang, Shuran ; Wu, Lixing ; Mi, Nana ; Liu, Yanfeng ; Ding, Feng ; Tong, Huangjin

Acetyl-coenzyme A carboxylase (ACC) and diacylglycerol acyltransferase 2 (DGAT2) are recognized as potential therapeutic targets for nonalcoholic fatty liver disease (NAFLD). Inhibitors targeting ACC and DGAT2 have exhibited the capacity to reduce hepatic fat in individuals afflicted with NAFLD. However, there are no reports of dual inhibitors targeting ACC and DGAT2 for the treatment of NAFLD. Here, we aimed to identify potential dual inhibitors of ACC and DGAT2 using an integrated in silico approach. Machine learning-based virtual screening of commercial molecule databases yielded 395,729 hits, which were subsequently subjected to molecular docking aimed at both the ACC and DGAT2 binding sites. Based on the docking scores, nine compounds exhibited robust interactions with critical residues of both ACC and DGAT2, displaying favorable drug-like features. Molecular dynamics simulations (MDs) unveiled the substantial impact of these compounds on the conformational dynamics of the proteins. Furthermore, binding free energy assessments highlighted the notable binding affinities of specific compounds (V003-8107, G340-0503, Y200-1700, E999-1199, V003-6429, V025-4981, V006-1474, V025-0499, and V021-8916) to ACC and DGAT2. The compounds proposed in this study, identified using a multifaceted computational strategy, warrant experimental validation as potential dual inhibitors of ACC and DGAT2, with implications for the future development of novel drugs targeting NAFLD.

News (Medical) associated with Ervogastat

09 Jan 2026

·www.fiercebiotech.com

Madrigal pays $50M for Pfizer MASH drug with eye on Rezdiffra combo potential

The plan for this year is to conduct a drug-to-drug interaction study of ervogastat with Rezdiffra as well as consult with the FDA on the design of a phase 2 combination trial.\n Madrigal has paid Pfizer $50 million for the rights to a DGAT2i inhibitor with the intention of combining the drug with its approved liver disease med Rezdiffra.Madrigal’s thyroid hormone receptor-beta (THR-beta) agonist Rezdiffra became the first-ever drug to be approved by the FDA for metabolic dysfunction-associated steatohepatitis (MASH) back in 2024. The therapy has proven a hit for the company, which is expecting full-year sales for 2025 to top $1 billion.The idea behind acquiring Pfizer’s DGAT2i inhibitor, called ervogastat, is to expand Rezdiffra’s potential. The plan for this year is to conduct a drug-to-drug interaction study of ervogastat and Rezdiffra as well as consult with the FDA on the design of a phase 2 trial for a combination treatment of both drugs.DGAT-2 inhibitors block the final step in triglyceride assembly and storage, resulting in lower hepatic triglycerides, reduced lipotoxic fat and decreased inflammation, Madrigal explained in the Jan. 9 release.“This differentiated mechanism offers the potential for additive clinical benefit when combined with Rezdiffra, a THR-β agonist that increases the cell’s ability to process fat via mitochondrial biogenesis,” the biopharma added.Madrigal also pointed to phase 2 data showing that 72% of patients treated with 150 mg ervogastat achieved at least a 30% reduction in liver fat, while 61% achieved at least a 50% reduction.Ervogastat was an asset in need of a good home. In November, Pfizer announced it was ending work on a MASH combination treatment of ervogastat and an acetyl-CoA carboxylase inhibitor called clesacostat. While Pfizer continued to list ervogastat in its pipeline as a monotherapy, there didn’t appear to be any further trials planned for the drug. In return for the license to ervogastat—along with the rights to two undisclosed early-stage MASH assets—Madrigal has handed over $50 million upfront. While potential milestone payments are also attached to the deal, the companies didn’t share those details.“Our global license agreement for ervogastat aligns with our long-term leadership ambition, and we believe Madrigal is uniquely positioned to advance this promising phase 2 asset and unlock its full clinical and commercial value through a development program focused on combination therapy with Rezdiffra,” Madrigal CEO Bill Sibold said in this morning’s release.Madrigal may have been the first to score an approval for the tricky indication of MASH, but there is plenty of competition on the horizon—including from Novo Nordisk’s GLP-1 Wegovy, which gained an FDA label expansion for the disease last year.“MASH is a complex disease that will require multiple treatment approaches to address the full spectrum of patient needs,” Madrigal’s Chief Medical Officer David Soergel, M.D., said in today’s release.“With Rezdiffra as the anchor and a world-class R&D team, our broadened portfolio now spans several key pathways that will define the future of MASH treatment,” Soergel added. “Along with studies of our oral GLP-1 receptor agonist, we look forward to adding ervogastat to our growing clinical program.\"

Phase 2License out/inClinical ResultDrug ApprovalAcquisition

09 Jan 2026

·endpoints.news

Venture firm a16z raises $700M; Ribo Life's $230M Hong Kong IPO

Plus, news about Madrigal, Pfizer, Aquestive and Ascendis: 💰 a16z re-ups its biotech capital pool: The storied VC firm raised $700 million for its Bio + Health strategy, representing a sliver of the more than $15 billion in funds collected across multiple investing arms. The firm’s a16z Bio + Health team is led by Vineeta Agarwala and last announced a $500 million fund in collaboration with Eli Lilly last January. — Kyle LaHucik 🇭🇰 Ribo Life Science lists on Hong Kong exchange : The siRNA company roped in more than $230 million from the IPO ($1.8 billion Hong Kong dollars), which it described as significantly oversubscribed, both from local and international investors. The company is advancing more than half a dozen clinical-stage assets, largely spanning cardiometabolic and renal diseases. — Max Bayer 💰 Madrigal snags MASH candidate from Pfizer : The Rezdiffra maker paid $50 million upfront to the larger pharma for ervogastat, with an undisclosed amount of milestone payments on the table. The clinical-stage asset is a DGAT-2 inhibitor, a mechanism that Madrigal says could be additive on top of Rezdiffra, its approved drug for the fatty liver disease. Pfizer previously received FDA fast track designation for ervogastat as part of a combo regimen with another molecule. — Max Bayer 📉 Aquestive gets FDA feedback noting “deficiencies”: The biotech’s CEO, Dan Barber, said in a statement that regulators found unspecified deficiencies that “preclude discussion of labeling and post-marketing commitments at this time.” Aquestive is attempting to get approval for a drug called Anaphylm, which is a treatment for severe allergic reactions that’s placed under the tongue. Aquestive noted that the review remains ongoing, and the PDUFA date is Jan. 31. The company’s stock $AQST fell about 40% Friday morning. — Max Gelman Error: Survey not found. 📊 Ascendis reports one-year achondroplasia data after FDA delay: The company said its drug TransCon CNP induced an average annualized growth velocity of 8.8 cm in patients receiving treatment for the first time, and 8.42 cm in previously treated patients. Friday’s data come after the FDA extended its review deadline for TransCon CNP last November. A decision is now expected by the end of February. — Max Gelman

IPOFast Track

09 Jan 2026

·firstwordpharma.com

Madrigal scoops Pfizer's shelved MASH drug

Already at the head of the metabolic dysfunction-associated steatohepatitis (MASH) pack, Madrigal Pharmaceuticals is looking to firm up its position with a new deal for a pipeline asset recently cast aside by Pfizer.On Friday, Madrigal said it struck an exclusive global licensing agreement with Pfizer for ervogastat, a Phase II oral DGAT-2 inhibitor that had previously been part of the latter's internal MASH programme and was being developed as a combination with clesacostat, a liver-targeted inhibitor of acetyl-CoA carboxylase (ACC), before being shelved late last year.Madrigal will pay Pfizer $50 million upfront, with additional unspecified milestone payments and royalties tied to future development and sales.Madrigal's Rezdiffra (resmetirom) was the first FDA-approved treatment for non-cirrhotic MASH patients when it was cleared in 2024. The THR-β selective agonist, also approved in Europe, generated $287.3 million in its most recently reported quarter and is tracking toward $1 billion in annual revenues, CEO Bill Sibold has said."With Rezdiffra as the anchor…our broadened portfolio now spans several key pathways that will define the future of MASH treatment," David Soergel, chief medical officer, said in a release Friday. "Along with studies of our oral GLP-1 receptor agonist, we look forward to adding ervogastat to our growing clinical programme."Combo possibilitiesErvogastat targets the final stage of how the liver assembles and stores triglycerides, interrupting the process before toxic fat can accumulate, trigger inflammation and damage liver tissue. Madrigal cited a published Phase II study where 72% of patients treated with a 150-mg dose of ervogastat saw their liver fat drop by at least nearly a third, while 61% achieved reductions of half or more, as measured by MRI-PDFF scans. Patients also showed better liver enzyme levels and reduced liver stiffness on vibration-controlled transient elastography, and all active doses were well tolerated."Because Rezdiffra and ervogastat act on distinct yet complementary pathways that drive liver fat accumulation, this combination has potential to produce additive antisteatotic and antifibrotic efficacy," said Quentin Anstee, lead investigator on the Phase II study.Madrigal plans to conduct a drug-to-drug interaction study with Rezdiffra this year and consult with the FDA on the design of a possible Phase II combination trial.Last July, Madrigal bet up to $2.1 billion for exclusive worldwide rights to a GLP-1 agonist called SYH2086 under an agreement with CSPC Pharmaceutical in a bid to create a best-in-class oral combination therapy for MASH.Despite being first with a marketed treatment for MASH, Madrigal is no longer alone after Novo Nordisk's Wegovy (semaglutide) was granted an accelerated FDA approval — a first for a GLP-1 drug in the disease — last August (see – KOL Views Q&A: Wegovy and Rezdiffra could be friends with mutual benefits in MASH). Eli Lilly has also been trying to capture a piece of the MASH pie with its dual GLP-1/GIP drug tirzepatide.

Phase 2Drug ApprovalLicense out/inClinical ResultAccelerated Approval

100 Deals associated with Ervogastat

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 2	China	Pfizer Inc.	15 Jun 2020
Fibrosis	Phase 2	Hong Kong	Pfizer Inc.	15 Jun 2020
Fibrosis	Phase 2	Taiwan Province	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	United States	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	Japan	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	Bulgaria	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	Canada	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	India	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	Poland	Pfizer Inc.	15 Jun 2020
Fibrosis, Liver	Phase 2	Puerto Rico	Pfizer Inc.	15 Jun 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04321031 (MIRNA, CTgov)	Phase 2	Metabolic Dysfunction Associated Steatohepatitis \| Fibrosis	256	Placebo	hwpzlvvaxp(htpexcfcxt) = pjyjbcmwxk cdvjplgsxl (hcypfzjrqg, uhcpelmmcm - fcedpvohij) View more	-	21 Mar 2025
NCT04866225 (CTgov)	Phase 1	-	6	[14C]PF-06865571 ([14C]PF-06865571 300 mg Oral)	voobbakhku(wizxmywimx) = ynnedvryui nwmtyghbhs (jrziabxytd, 16.3) View more	-	31 Jul 2024
NCT04866225 (CTgov)	Phase 1	-	6	PF-06865571 (PF-06865571 300 mg Oral & [14C]PF-06865571 100 μg IV)	voobbakhku(wizxmywimx) = fyqaeeubkz nwmtyghbhs (jrziabxytd, 15.8) View more	-	31 Jul 2024
NCT04399538 (CTgov)	Phase 2	Metabolic Dysfunction Associated Steatohepatitis	75	Placebo	kikjcbyutx(crkbzlqjrn) = ytoerbdbst dfowhzwvgl (smgdmatmkm, hrjuakewnj - uetknkjbmf) View more	-	13 Apr 2023
NCT03776175 (CTgov)	Phase 2	Metabolic dysfunction-associated steatotic liver disease	99	Placebo	ohqcpszcdu(dkveiledsk) = zlmpvfxvcn juhmrrwoho (eyigwoiuga, lcamsrbpnt - ppvwqvaich) View more	-	23 Sep 2020
NCT03513588 (CTgov)	Phase 1	Metabolic Dysfunction Associated Steatohepatitis	48	Placebo	edbjoamjvz(gantvlkdak) = iawvxasdmz ciulunwbho (kballhrcwk, bhpgncwcju - hnaiaczcky) View more	-	13 Mar 2020

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