Liver health and noninvasive assessment

Source date: 2026-11-08. Evidence: Sponsor numerical account with simultaneous paper publication; full paper not appraised. Appraisal: November 10 scheduled run, completed November 11 UTC; source dates are not retrieval dates.

Regeneron’s November 8 AASLD account reports 30 active and 10 placebo recipients in four single-dose groups of the first-human ALN-CIDEB/CIDEB-siRNA Phase 1/2 program. At week 36, active groups had 58–80% liver-fat reductions from baseline by MRI-PDFF versus 2.9% mean reduction with placebo. These are not 58–80% placebo-adjusted effects. The report says 62% of active recipients had liver fat <5%; that is an imaging threshold, not histologic MASH resolution.

This adds longer follow-up to the saved October abstract. The earlier abstract described 47 participants, while this report describes a 40-person analysis; the manuscript’s cohort/visit flow has not been fully appraised, so the difference is not labeled seven withdrawals. Exact dose/visit denominators, intervals and formal between-group analyses remain gaps. The sponsor announces simultaneous NEJM publication; the numbers here come from the original sponsor account.

Safety: All events were mild/moderate except one serious severe hyperglycemia event, attributed by investigators to subsequently diagnosed adult-onset type 1 diabetes rather than study drug. No trial discontinuations or nausea/vomiting in the active groups were reported. Thirty exposed participants cannot establish superiority to GLP-1 drugs or long-term safety. Stage/U.S. status: Investigational; ongoing histology/safety trials are separate from this liver-fat surrogate. Fewer clinical liver complications are not demonstrated.

Next milestones: Full paper/biopsy and longer clinical-outcomes appraisal; future trial completion is distinct from publication.

Sources: investor.regeneron.com · news release; ClinicalTrials.gov · NCT06836609; ClinicalTrials.gov · NCT07854782.

Coverage and remaining gaps: Focused, incomplete review. All pages of the specified U.S. registry discovery and saved identifiers were retrieved; retrieval is not full appraisal. Global registers, every paper/supplement and the complete regulatory/harms census remain incomplete. Full-success and baseline flags stay unchanged. Run record.

Source date: 2026-11-05. Recorded in this review: November 6, 2026.

Evidence: Sponsor-reported observational conference analyses.

What changed: Madrigal’s November 5 AASLD release reports paired elastography data at about one year: Truveta 150 patients, 55%with≥25%stiffness improvement; Trio 195,45%; GastroHealth/Latica 112,47%; Methodist 35,37%. Improvement plus stabilization reached 83–93% across these cohorts. These are separate cohorts, not a pooled trial or biopsy-proven fibrosis reversal. In separate pharmacy/claims analyses, persistence reached up to 72%at 12 months using a 60-day treatment-gap definition.

Limitations: Sponsor-reported observational conference evidence without randomized untreated controls; paired-measurement selection, concomitant therapies and incomplete follow-up limit causal interpretation. No established reduction in cirrhosis, transplantation, CV events or mortality follows from lower stiffness or LDL. Complete original abstracts, denominators for all secondary/safety analyses and confounding methods remain unappraised.

Safety: The GastroHealth/Latica analysis reports 11%with≥1 treatment-related AE: diarrhea 7%, nausea 4%, pruritus 2%, vomiting 2%, fatigue≤1%. Its full safety denominator is not supplied in the release; observational capture may miss events and cannot establish superiority to trial safety.

U.S. status: Rezdiffra has its existing approved noncirrhotic F2–F3 MASH indication; these observations add no cirrhosis indication.

Next milestones: Full AASLD tables and long-term outcomes: date unknown (No firm publication date verified)

Sources: Primary source.

Source date: 2026-04-09. Recorded in this review: November 6, 2026. Related event date: 2026-03-26. Historical baseline; not a new-news alert.

Evidence: Recovered historical regulator authorization.

What changed: EMA confirms Kayshild (weekly injected semaglutide) received EU conditional marketing authorization March 26,2026 for adults with noncirrhotic MASH and F2–F3 fibrosis, alongside diet/activity. This is recovered regulatory context, not a new November approval. It is a separate EU brand/authorization from Wegovy’s weight-management product.

Limitations: Conditional authorization relies on biopsy endpoints; long-term liver-related clinical benefit remains under confirmation. Country-level launch/reimbursement was not verified.

Safety: GI effects and fatigue are common; no new safety tables were released in this check.

U.S. status: This EU brand fact does not change existing U.S. Wegovy injection MASH approval or create an oral MASH approval.

Next milestones: No firm next date verified.

Sources: Primary source; Primary source.

Source date: 2026-11-04. Recorded in this review: November 6, 2026.

Evidence: Sponsor regulatory clarification; original informal question only partly resolved.

What changed: Novo’s November 4 SEC report says CHMP issued a positive opinion for a Wegovy label update containing ESSENCE mode-of-action and pharmacokinetics information. It distinguishes that update from the separate Kayshild MASH authorization. This partly clarifies the saved September 18 Reddit question about omission from CHMP highlights; it does not supply the opinion’s exact date or explain that omission.

Limitations: The original September-procedure minutes could not be retrieved; sponsor wording is not a new European Commission indication authorization. Do not infer that Wegovy now has an EU MASH indication merely from clinical-data label language.

Safety: No new safety result.

U.S. status: U.S. injected Wegovy MASH status is unchanged; oral-semaglutide MASH review is separately forecastH1 2027, not approved.

Next milestones: Oral semaglutide MASH U.S. decision: 2027-H1 (Sponsor forecast November 4)

Sources: Primary source; Primary source.

Coverage and remaining gaps: focused_incomplete; Focused incomplete appraisal. All pages of specified ClinicalTrials.gov discovery were downloaded, plus all176 unique saved named IDs across these ten topics; retrieval does not equal appraisal. Full worldwide literature/non-U.S.-registry, regulatory-label, harms/hold/discontinuation census and original conference/podcast recordings remain incomplete. Preserve full successful-check timestamps and incomplete sleep baseline flags.; Full new AASLD abstracts/posters, semaglutide/resmetirom comparative RWE and complete cirrhosis/noninvasive test census remain unappraised. September CHMP minutes inaccessible; the new sponsor statement does not prove an EU Wegovy MASH indication or explain the omission.

Informal-source coverage: Original September 18Wegovy/CHMP post reread; Nov4sponsor statement partly clarifies label context, exactSeptemberprocedure/omission unresolved. AASLD commentary/full interviews not exhaustively appraised.

Full coverage record.

Source date: 2026-11-03. Recorded in this review: November 3, 2026.

Corcept's MONARCH (NCT06108219) enrolled 175 participants. Cohort A randomized 82 with biopsy-confirmed MASH 2:1 to miricorilant 100 mg twice weekly or placebo for 48 weeks; cohort B randomized 93 with presumed MASH 2:1 to 100 mg twice weekly for six weeks then 200 mg twice weekly for 18 weeks, or placebo.

The sponsor reports greater liver-fat reduction at 200 versus 100 mg twice weekly and describes 19% fibrosis improvement among cohort-A participants with paired biopsies. It does not provide the paired-biopsy denominator, placebo rate, histology response definition, effect interval or numerical liver-fat effects. The release does not define precisely what the 19% quantifies, including whether it is a responder proportion. The 19% must not be interpreted as a 19-percentage-point placebo-adjusted benefit or reversal of cirrhosis.

The release describes adverse-event rates as similar to placebo but supplies no arm-level event counts or serious-harm table. A further Phase 2 trial at 100 mg daily is planned soon; registry/protocol and actual initiation were not verified. These incomplete toplines require full results before judging efficacy or comparative safety.

U.S. status: Miricorilant remains investigational for MASH in the U.S.

Next milestones: Miricorilant higher-dose Phase 2 initiation: date unknown (Sponsor forecast: soon; exact date unknown).

Sources: ir.corcept.com · news release; ClinicalTrials.gov · NCT06108219.

Source date: 2026-11-03. Recorded in this review: November 3, 2026.

Madrigal plans MAESTRO-CSPH, another Phase 3 event-driven resmetirom outcomes trial in more than 2,000 people with well-compensated MASH cirrhosis (F4c), enriched for clinically significant portal hypertension. Initiation is forecast for H1 2027, subject to regulatory discussions.

This is distinct from ongoing MAESTRO-NASH OUTCOMES, whose data are now forecast for late 2027. No MAESTRO-CSPH registration, exact composite, dose allocation, actual first treatment or result was verified. The sponsor also plans noninvasive-biomarker validation; biomarker validation and fewer decompensation/transplant/death events remain separate questions.

Rezdiffra's established noncirrhotic F2–F3 indication does not cover cirrhosis. The new trial announcement and result forecast do not establish cirrhosis efficacy or approval.

U.S. status: Resmetirom is investigational for this cirrhosis indication despite Rezdiffra approval in noncirrhotic F2–F3 disease.

Next milestones: MAESTRO-CSPH planned initiation: 2027-H1 (Sponsor forecast, conditional on regulatory discussions); MAESTRO-NASH OUTCOMES result window: 2027 (Sponsor forecast: late 2027 (year precision; no exact month/day)).

Sources: madrigalpharma.gcs-web.com · news release; ClinicalTrials.gov · NCT05500222.

Source date: 2026-11-02. Recorded in this review: November 3, 2026. Related event date: 2026-10-28.

Two distinct developments: Regeneron's October 30 announcement and the AASLD abstract describe a randomized placebo-controlled first-human ALN-CIDEB study (NCT06836609), while the November 2 registry update confirms a separate Phase 3 start.

The preliminary abstract reports 47 participants across single-dose groups: mean liver-fat reduction reached approximately 70% from baseline at week 12, persisting through week 24. ALT declined 18–35% across doses. All treatment-emergent events were mild/moderate except one severe serious hyperglycemia event judged unrelated by the investigator. Exact group/visit denominators, CIs and complete comparative harms are not available. Relative liver-fat reduction is not fibrosis improvement or fewer clinical complications.

The separate Phase 3 NCT07854782 now records recruiting and an actual October 28 start, planning 1,500 adults, two ALN-CIDEB dose levels versus placebo, with primary treatment-emergent adverse-event occurrence/severity through week 64. Numerical doses are not posted. Primary/final completion remains estimated March 3, 2029. The early result was disclosed October 30, not newly measured November 2; the larger trial has no results.

U.S. status: ALN-CIDEB remains investigational; no U.S. marketing approval.

Next milestones: ALN-CIDEB Phase 3 primary/final completion: 2029-03-03 (Registry estimate; publication date unknown).

Sources: investor.regeneron.com · news release; DOI · 10.1097/hep.0000000000001842; ClinicalTrials.gov · NCT06836609; ClinicalTrials.gov · NCT07854782.

Coverage and remaining gaps: focused_incomplete. Paginated retrieval is not complete appraisal. Not every returned record, all non-U.S. registers, full papers/supplements, conference audio or original podcasts were reviewed; full successful-check timestamps and incomplete baseline flags must remain unchanged.; MONARCH sponsor language does not give a placebo fibrosis rate, paired-biopsy denominator, responder definition, CI or complete safety table; the 19% claim is not made into a placebo-adjusted effect.; ALN-CIDEB abstract is preliminary; detailed dose-group/visit denominators, intervals and full harms are unavailable. MAESTRO-CSPH final registry/protocol and initiation remain unverified.

Informal-source coverage: Original saved Reddit/statement chains selectively revisited; no distinct new source-grounded rumor or material status transition selected. Long-form podcasts and talks were not exhaustively reviewed.

Full coverage record.

Source date: 2026-10-28. Recorded in this review: October 30, 2026.

The October 28 results posting for FORTUNA / NCT05809934 reports a 52-week study of monthly AZD2693 25 mg or 50 mg versus placebo in noncirrhotic NASH/MASH with fibrosis and the PNPLA3 I148M risk variant. The enrollment field is 220; participant-flow and safety groups contain 73, 69 and 74 treated participants.

At week 54, NASH resolution without fibrosis worsening occurred in 4/73, 1/69 and 5/74, respectively. Adjusted odds ratios versus placebo were 0.83 (95% CI 0.21–3.23), p=0.783, and 0.20 (0.02–1.78), p=0.116. Neither dose met this primary endpoint. At least one-stage fibrosis improvement without NASH worsening was 12/73, 6/69 and 8/74; neither comparison was significant (OR 1.64 [0.62–4.37] and 0.80 [0.26–2.44]).

Serious events through week 64 affected 7/73, 3/69 and 7/74; no deaths were reported. The study actually completed September 29, 2025. October 28 is the registry-results posting date, not the treatment-completion date or necessarily the first public disclosure anywhere. These biopsy results do not demonstrate fewer cirrhosis complications, and no program discontinuation was verified.

U.S. status: AZD2693 remains investigational for MASH; no U.S. approval or verified program-discontinuation announcement identified.

Next milestones: Peer-reviewed FORTUNA report or clarified development decision: date unknown (Date unknown).

Sources: ClinicalTrials.gov · NCT05809934.

Source date: 2026-10-28. Recorded in this review: October 30, 2026.

RED-C-3132 / NCT05297448 randomized 517 adults with cirrhosis and medically controlled ascites to rifaximin SSD immediate-release 40 mg twice daily (255) or placebo (262), for up to 72 weeks. This formulation and primary-prevention question differ from approved rifaximin 550 mg regimens used to reduce recurrence.

The October 28 posting reports 22 versus 21 first adjudicated overt-hepatic-encephalopathy events requiring medical intervention or deaths, with HR 0.89 (95% CI 0.48–1.65), p=0.7138. The primary endpoint was not met. The event table contains unusual confidence-limit fields attached to counts; the quoted interval is the stated hazard-ratio analysis, not an interval on those counts.

The safety module lists zero serious and zero other adverse events while separately reporting 7/255 versus 8/262 deaths. Those internally problematic/incomplete fields cannot establish absence of adverse events or a safety advantage. The study actually completed February 24, 2026; October 28 is the results-posting date. Registry reporting does not establish a new U.S. indication or clinically useful prevention.

U.S. status: This result does not change existing rifaximin approvals or establish approval of the SSD 40 mg formulation for first-event prevention.

Next milestones: Clarification or full publication of RED-C-3132 safety data: date unknown (Date unknown).

Sources: ClinicalTrials.gov · NCT05297448.

Source date: 2026-10-28. Recorded in this review: October 30, 2026.

Two separate randomized placebo-controlled studies at Tanta University were first posted October 28, each planning 60 participants and three months of therapy on top of conventional care. NCT07900100 tests rupatadine 10 mg daily; NCT07900087 tests roflumilast 0.5 mg daily. Both are labeled Phase 2/3 in the registry.

Their primary outcome is a change in ultrasound steatosis grade, not biopsy-proven fibrosis regression or prevention of liver failure. Both records are not yet recruiting. Rupatadine's estimated October 25 start has elapsed without a verified actual start; roflumilast estimates November 1. Estimated primary completions are June 20, 2027 and August 1, 2027, respectively. These are early repurposing questions, not evidence that existing allergy/COPD prescribing should change.

U.S. status: No U.S. MASLD/MASH indication established for either therapy by these protocols.

Next milestones: Rupatadine MASLD primary completion: 2027-06-20 (Registry estimate); Roflumilast MASLD start: 2026-11-01 (Registry estimate); Roflumilast MASLD primary completion: 2027-08-01 (Registry estimate).

Sources: ClinicalTrials.gov · NCT07900100; ClinicalTrials.gov · NCT07900087.

Coverage and remaining gaps: Focused partial appraisal through October 30, 2026. Complete retrieval of the specified query and saved named records; incomplete worldwide review. No full successful-check or baseline-completion claim.. Focused appraisal only. All pages of the specified ClinicalTrials.gov query were retrieved, but not every returned record underwent full results/harms appraisal. This is not complete worldwide coverage.; Independent non-U.S. registry searches, a comprehensive publication/hold/discontinuation census, and complete original conference/podcast audio and transcripts remain incomplete. Full successful-check timestamps and incomplete sleep baseline flags must remain unchanged.; Full AZD2693 study-report/publication reconciliation remains incomplete; the October 28 date identifies ClinicalTrials.gov posting, not necessarily the first public disclosure anywhere.; RED-C-3132 safety fields are internally problematic/incomplete and require clarification before comparative-safety conclusions.; Original AASLD November 5–9 full abstracts and all announced analyses were not comprehensively appraised; scheduled presentations are not delivered results. September CHMP MASH-procedure outcome remains unresolved.

Informal-source coverage: Re-read the original Reddit post about the September CHMP Wegovy MASH agenda omission and current EMA EPAR. The original inference remains unresolved; absence from the retrieved indication summary does not establish rejection. Other MASH rumor searches were selective.

Full coverage record.

Source date: 2026-10-27. Recorded in this review: October 27, 2026.

New registry tables for NCT06104319 describe 61 participants in four single-dose GSK4532990 groups (25/200/400/800 mg SC; 17/15/15/14 participants). This was an open-label dose-exploration study with no separate placebo arm, completed September 23, 2025.

The primary readouts are PK/PD-model-predicted HSD17B13 protein/mRNA changes based on biopsy and exposure data, not observed fibrosis reversal or clinical outcomes. For example, the 800-mg model predicts protein reduction of 88.79% (95% CI 82.12–91.71) at week 8 and 75.27% (66.83–81.16) at week 28. These are simulated estimates; the table's six simulated individuals per dose/time are not six actual trial participants. The mRNA description calls its uncertainty a prediction interval while metadata says confidence interval, so these must not be treated as interchangeable clinical estimates.

Serious events occurred in 1/17, 0/15, 1/15 and 0/14, respectively, with no deaths; the 400-mg event included increased hepatic enzymes. Small uncontrolled safety counts do not establish long-term safety. This is target engagement, not proof of improved MASH histology, fewer liver complications or approval.

U.S. status: Investigational HSD17B13-directed therapy; no U.S. approval established.

Next milestones: Controlled histology/clinical-outcome evidence for GSK4532990: date unknown (Not established by this study).

Sources: ClinicalTrials.gov · NCT06104319.

Related findings, recorded once: PM647a prime-editing program enters the AAT-deficiency registry (primary source); FDA approves Hibsago for selected adults with chronic hepatitis B (primary source). Hibsago FDA prescribing information retains the eligibility, boxed-warning and efficacy-denominator details.

Coverage and remaining gaps: Focused partial review; all pages of specified ClinicalTrials.gov discovery retrieved and selected relevant records appraised. Worldwide full-topic review and baseline completion are NOT claimed.. Focused partial appraisal only. Complete ClinicalTrials.gov query retrieval is not exhaustive worldwide evidence review; independent non-U.S. registries, full conference audio/slides, all publications and a complete holds/discontinuations/harms census remain incomplete. Do not advance full successful-check timestamps or sleep baseline-complete flags.; GSK4532990 results are model-predicted target engagement, not measured fibrosis/outcome efficacy. Detailed follow-on program context remains incomplete.; Wegovy EMA product-information PDF updated October 26 was downloaded: section4.1 remains weight-management indications. This does not explain the September CHMP agenda omission; the underlying procedural outcome remains unresolved.; Hibsago FDA October20 approval and PM647a first human AAT trial are root-owned; cross-link those findings rather than duplicate.

Informal-source coverage: Re-read original September18 NovoNordisk_Stock Wegovy-MASH agenda post. Current EMA EPAR/October26 PI does not establish the claimed procedural outcome; no confirmation/retraction inferred from omission. Targeted informal searches sampled MASH/FGF21/metabolic-liver leads; no other new claim promoted.

Full coverage record.

October 16 registry updates list recruiting status for two resmetirom studies. NCT07830758 is a planned 90-person randomized phase 1b study in MASH with HFpEF, comparing resmetirom with placebo over 24 weeks; safety and MRI-PDFF are primary outcomes. Its September 2026 start was still an estimate in the October 20 snapshot, so recruiting status should not be converted to confirmed first dosing. Primary completion is estimated November 2027 and final completion December 2027.

NCT07848191 is a planned 150-person open-label, nonrandomized phase 4 study with six cohorts examining resmetirom alone or with dapagliflozin/pioglitazone, including 28-week safety. It records an actual October 7 start and estimated November 2027 primary/final completion. These studies do not establish heart-failure benefit, drug-combination superiority or expanded U.S. indications. Liver-fat biomarkers and tolerability must be distinguished from fibrosis, clinical liver events, heart-failure outcomes and survival.

Sources: ClinicalTrials.gov · NCT07830758; ClinicalTrials.gov · NCT07848191.

Coverage and remaining gaps: Focused incomplete coverage. All pages of the specified ClinicalTrials.gov discovery query and saved named records were retrieved on 2026-10-20; retrieval is not exhaustive appraisal of every record or worldwide evidence. Do not advance full successful-check timestamps. Original source dates remain unchanged. Independent non-US registries, complete conference tables/audio, and a comprehensive harms/discontinuation census remain incomplete.; ClinicalTrials.gov discovery: 150 records across 2 retrieved pages; final retrieval errors: []. Named records also retrieved successfully.; Sleep incomplete baselines used 90-day context through October 20; other topics used the last full successful check minus seven days. Earlier October 16 focused checks did not reset that window.; DR10624 liver-fat finding is owned by cardiovascular and cross-linked here; do not duplicate the event. New resmetirom protocols are recovered baseline context, not an October 23 result.; October 23 bounded search of Madrigal releases/pipeline recovered existing plans, not a newly appraised clinical readout. Complete MASH conference/negative-data review remains open.; October 23 was a bounded source follow-up only; broad registry discovery remains the October 20 snapshot. No full successful check is claimed.

Informal-source coverage: Original informal sources were sampled on October 20; not a comprehensive podcast, social-media, or anonymous-source search. Reposts were not treated as independent confirmation. No resolved claim was inferred from source silence. Revisited September 18 Wegovy/CHMP omission thread and current EMA overview. Omission does not establish rejection or resolve the MASH procedure; no status change verified.

Full coverage record.

NCT07878091 / Kylo-0603-IIa-01, first posted October 16. Shanghai Chia Tai Tianqing sponsors a masked randomized Phase 2a trial in 120 adults with MASLD and overweight/obesity in China, comparing daily oral Kylo-0603 8, 12 or 16 mg with placebo for 12 weeks.

Kylo-0603 is described as a liver-targeted GalNAc-conjugated thyroid-hormone receptor β agonist. Primary is percentage change in MRI-PDFF liver-fat content at week 12. Secondary measures include liver stiffness, LDL cholesterol, liver enzymes and other biomarkers. Neither liver-fat reduction nor a stiffness/LDL change alone establishes fibrosis reversal, fewer liver complications or cardiovascular benefit.

The record is not yet recruiting. Start November 15, 2026 and primary/final completion August 15, 2027 are estimates; no results or participant adverse-event rates are posted. Earlier healthy-volunteer work is historical context, not a new October efficacy result. No U.S. approval or availability is established.

Sources: ClinicalTrials.gov · NCT07878091; www1.hkexnews.hk · PDF document.

Remaining gaps: Read current canonical scope, shared summaries, state and assigned topic notes. Bounded registry discovery covered September 5–October 16, 2026; prior October 13 findings were deduplicated. Full-topic successful-check dates remain unchanged.; Retrieved all 144 records across 2 pages of the bounded ClinicalTrials.gov query, plus 13 named records. Selected relevant new/changed protocols were appraised; downloading all records does not establish exhaustive safety/results review.; Europe PMC original-literature discovery failed with HTTP 503 for this topic. Targeted primary-source web searches supplied a partial fallback. Worldwide literature, regulators, international registries and complete original conference/podcast recordings remain incomplete.; The new Kylo-0603 patient trial is the selected formal entrant. Prior TRUTH, ARO-INHBE, ALN-CIDEB and efimosfermin findings were deduplicated. Current EMA Wegovy overview still does not resolve the saved September MASH variation; no approval/rejection inferred from omission. Full papers/supplements, clinical-outcomes and noninvasive-test utility census remain gaps.

Informal-source coverage: Saved Wegovy CHMP omission inference revisited against EMA current page; outcome remains unconfirmed and no repeat alert. Targeted informal searches supplied no separate new original claim selected. Complete conference/investor audio and informal source census remain incomplete.

Full coverage record.

Baseline recovery, checked October 13 — NEBULA-1, NCT07701993 / GSK 306300. GSK's randomized masked placebo-controlled Phase 3 trial plans 1,740 adults aged 18–75 with compensated MASH cirrhosis. Efimosfermin alfa is an investigational FGF21 analogue given subcutaneously.

Primary is time to an adjudicated composite of all-cause mortality, liver transplantation and significant hepatic decompensation, over up to 356 weeks. Liver stiffness, ELF, metabolic measures, quality of life and harms are secondary; biomarker improvement alone will not prove this primary benefit.

The September 30 registry and original GSK protocol say recruiting, with actual start July 22, 2026. Estimated primary completion is June 23, 2033, final August 24, 2033. No results; U.S. treatment remains investigational. This earlier program fills a saved coverage gap rather than a new October launch.

A secondary CTIS mirror displays an October 12 EU authorization date and a different 1,468 planned total; the primary EMA linked search did not expose the decision details. That regional claim/count is not promoted as verified or substituted for the source-backed 1,740 protocol count.

Sources: ClinicalTrials.gov · NCT07701993; gsk-studyregister.com · source page; euclinicaltrials.eu · source page; GSK Q1 2026 update.

Remaining gaps: Read current canonical scope, shared summaries/state and assigned topic notes. September 5–October 13 overlap preserves the September 12 full-review dates; October 6/9 entries were deduplicated. All pages of each bounded ClinicalTrials.gov query were downloaded, and named records plus selected relevant new/changed protocols were appraised. This is focused partial review, not a worldwide full literature/regulator/safety census; successful full-topic dates must remain unchanged.; Bounded query retrieved 138 records across 2 pages; incidental studies excluded. Named topic records refreshed: 12. Full older evidence, international registries, comprehensive harms and all original conference/podcast recordings remain gaps.; EMA current Wegovy overview and available minutes still do not resolve the September MASH variation. September minutes expected after the October CHMP; no rejection/delay inferred from omission. Secondary CTIS mirror NEBULA authorization not independently established from primary EMA; record discrepancy retained. Worldwide fibrosis/noninvasive utility and complete FGF21 harms corpus remain incomplete.

Informal-source coverage: Revisited saved September 18 Reddit inference about Wegovy CHMP omission against current EMA page and available agendas/minutes. Outcome remains unconfirmed; no repeat alert. Searched MASH informal development claims without selecting a new attributable original signal; full audio remains incomplete.

Full coverage record.

TRUTH / NCT05506488, published October 1; recovered in this October 9 overlap review. Amsterdam investigators randomized 31 people with fibrotic MASH (F2–F3) to intermittent dasatinib plus quercetin or placebo for 21 weeks.

Fibrosis improvement without MASH worsening occurred in 8/17 (47%) versus 1/14 (7%): risk difference 40 percentage points (95% CI 8.2–64.5), reported p=0.021. The reported risk ratio was 6.59 (95% CI 0.93–46.53); preserve this wide interval despite the different p-value method. MASH resolution was 9/17 (53%) versus 1/14 (7%), risk difference 46 points (95% CI 13.6–69.3).

Adverse events occurred in 82% versus 43%; one active participant stopped because of GI symptoms/fatigue. One serious event, planned knee surgery, was considered unrelated; severe dysphagia was attributed to previously undisclosed malignancy and that participant withdrew. Diabetes prevalence was imbalanced (76.5% versus 35.7%). Small size, short follow-up and biopsy surrogates limit inference: this does not establish fewer liver complications, a durable cure or lifespan extension. The combination has no U.S. MASH/longevity approval. Larger replication timing is undated.

Additional limitations: Four participants lacked follow-up biopsy and were counted as nonresponders in the primary analysis. A worst-case missing-data sensitivity gave RR 3.29 (95% CI 0.83–13.08), p=0.068. Noninvasive FIB-4, ELF and liver-stiffness comparisons were not significant. Histologic response is hypothesis-generating pending larger replication.

Sources: Primary source 1; Primary source 2.

Remaining gaps: Window: September 5–October 9, 2026, retaining the seven-day overlap from the last full successful check on September 12. October 6 findings were deduplicated.; 93 named NCT records across the ten topics and ten discovery queries downloaded successfully through the ClinicalTrials.gov public API. Download is not a claim that all fields/safety/results were exhaustively appraised.; Focused review only. Do not advance full successful-check timestamps or label incomplete remaining searches as no news.; Liver discovery returned 171 records; first 100 downloaded; selected relevant records screened, remaining page not reviewed. Updated saved RNA-interference protocols rechecked. September 29 TRIUMPH-1 full methods/CI access gap and worldwide noninvasive-screening/approval coverage remain.

Informal-source coverage: October 9 original r/Futurology post located: https://www.reddit.com/r/Futurology/comments/1x1lwvz/in_a_world_first_in_a_phase_2_trial_with_31/ . It frames histologic MASH resolution as a 50+% cure rate; original trial supports a short-term biopsy outcome, not proven durable cure. This is interpretation of a published paper, not a new clinical leak. Wider podcast audio and existing European Wegovy-MASH rumor not comprehensively refreshed.

Full coverage record.

Source/event date: October 6, 2026. Evidence: new phase 2 registration. AROINHBE-2001 plans 252 adults with suspected MASH, BMI 30–50, with or without diabetes and with stable background GLP-1/GIP therapy allowed. Randomized double-masked ARO-INHBE dose/schedule groups are compared with matched placebo. The primary endpoint is MRI-PDFF liver-fat change at week 48; histologic MASH resolution and fibrosis improvement are secondary. NOT_YET_RECRUITING; September 2026 start is still estimated and elapsed. Primary/final completion is estimated October 2029. No human results or safety estimates are posted. Registration establishes a liver development plan, not proven fibrosis benefit, fewer complications or U.S. approval.

ClinicalTrials.gov · NCT07859813 · ClinicalTrials.gov · NCT07859813

Source/event date: October 2, 2026. Evidence: new phase 3 registration. Regeneron’s ALN-CIDEB-MASLD-2604 plans 1,500 adults with MASLD and FibroScan liver stiffness 6–20 kPa. The randomized quadruple-masked study compares two ALN-CIDEB dose levels with placebo. Registered primary endpoints are incidence and severity of treatment-emergent adverse events through week 64; week-52 FibroScan fat/stiffness and liver enzymes are secondary. NOT_YET_RECRUITING, with November 6, 2026 estimated start and March 3, 2029 completion.

This registration does not show new human efficacy, clinical-event prevention, marketing approval or first dosing. MASLD inclusion by noninvasive stiffness is distinct from a biopsy-confirmed F2–F3 MASH pivotal population. The large phase designation does not convert biomarkers into clinical benefit; no results are posted.

ClinicalTrials.gov · NCT07854782 · ClinicalTrials.gov · NCT07854782

Source/event date: 2026-09-28. Evidence: Professional-society clinical guidance; not a new trial.

The September 28 EASL–EASD–EASO guidance addresses selection, initiation, monitoring and stopping of resmetirom and weekly semaglutide 2.4 mg as MASH-targeted treatments. It recommends individualizing choice by metabolic disease, body composition, other conditions and preferences; the strength of the recommendation should not be mistaken for high-certainty comparative evidence. This is an interpretation of existing evidence, not a new randomized head-to-head trial or proof of reduced liver-related deaths. Existing U.S. indications remain separate from European review and access. The guidance does not resolve the previously tracked September CHMP outcome. Further clinical-outcome follow-up remains necessary.

Next milestone: NATiV3 Q4 2026 sponsor forecast; ESSENCE clinical-event follow-up remains ongoing.

journal-of-hepatology.eu · article.

Related findings:

• DR10624 adds a triglyceride trial in diabetic kidney disease.

Source date: 2026-09-23. Event date: exact date not disclosed. Date basis: Announcement date; exact HSA action date not independently verified. Evidence: Sponsor announcement of regulatory approval.

Novo announced HSA approval of weekly injectable semaglutide 2.4 mg for adults with noncirrhotic MASH and F2–F3 fibrosis, with diet and activity. The decision draws on the existing ESSENCE week-72 biopsy evidence, not a newly completed outcomes trial.

Limitations: Not an indication for cirrhosis; geographic approval does not imply local stock or reimbursement. Liver-fat or biopsy improvement is separate from preventing decompensation, transplant or death. HSA decision letter was not independently retrieved.

Safety: No new safety analysis; known gastrointestinal tolerability and indication-specific prescribing information remain relevant.

U.S. status: Existing U.S. MASH approval is separate and unchanged.

Next milestone: ESSENCE part 2 continues to 240 weeks for liver-related clinical events; this release does not give a new readout date.

Novo Singapore approval announcement.

Source date: 2026-09-21. Event date: 2026-09-21. Evidence: Sponsor development forecast.

Novo plans a Phase 3 MASH program for UBT251 and a dedicated efruxifermin alcohol-related liver disease trial during 2027. The CMD presentation places UBT251 in F2–F3 disease and efruxifermin in advanced fibrosis/compensated cirrhosis. Existing SYNCHRONY OUTCOME results are forecast around 2030.

Limitations: Plans do not establish initiation or clinical benefit in the new indications. Historical efruxifermin biopsy data displayed in the presentation are not new September results.

Safety: No new safety dataset for the planned programs.

U.S. status: No U.S. approval established for UBT251 or efruxifermin.

Next milestone: UBT251 Phase 3 MASH and efruxifermin ALD study initiation: 2027 sponsor forecasts; specific dates and identifiers pending.

Novo Cardiovascular and liver CMD, slides 10, 18–19.

Source date: 2026-09-03. Evidence: Historical evidence recovered.

TGM-312 adds a liver-targeted SLC25A5 RNAi program to the watch. The phase 1/2 RESTORE-MASH study advanced from single-dose cohorts of healthy volunteers to multiple-dose cohorts of patients with MASH after a monitoring review. Four healthy-volunteer cohorts had been dosed; the participant count was not reported.

Limitations: No numerical human liver-efficacy findings were provided. Preclinical combination and fibrosis results remain animal evidence. The registry identifier was not verified.

Safety: The sponsor reports no serious or severe adverse events in the healthy-volunteer cohorts; this is limited early safety evidence.

U.S. status: Investigational.

Next milestone: The sponsor forecasts interim results from MASH patient cohorts during 2027.

Tangram September3 original release.

Source/event date: 2026-08-03. Date basis: Sponsor enrollment-initiation announcement. Evidence: Historical development baseline; not October news or a new efficacy readout.

Altimmune announced that enrollment had begun in PERFORMA, a global randomized, double-blind, placebo-controlled phase 3 trial of pemvidutide in MASH with moderate to advanced fibrosis. The program will assess fibrosis improvement, MASH resolution and clinical outcomes. Its current sponsor pipeline also describes active enrollment. This establishes a later MASH development stage than the older IMPACT phase 2b evidence; the obesity MOMENTUM results remain a separate indication and study.

Limitations and safety: Initiation does not establish efficacy, fewer liver complications or long-term safety. Histology and biomarkers remain distinct from clinical outcomes; the announcement is sponsor evidence, with no new outcome effect estimate. Breakthrough Therapy designation is not marketing approval.

U.S. status: Investigational; no pemvidutide approval established.

Next milestone: PERFORMA 52-week data forecast for 2029 by the sponsor, not a guaranteed publication or approval date.

Altimmune August 3 primary announcement; Current sponsor pipeline.