Novo Ends Two Ziltivekimab Heart-Failure Trials & SynAct Plans Another Arthritis Trial

Novo is ending two more heart-failure trials. Ziltivekimab still has a Phase 3 path after a heart attack, with a narrower evidence plan.

And SynAct wants another shot after two arthritis trials missed their main targets. This time, the argument turns on which patients enter the trial.

Welcome to The Pharma Closeout for Monday, September seventh. This edition is arriving late because of Monday's holiday. The news and previews reflect what we knew as of Monday. I'm Alex Mercer.

And I'm Maya Patel.

Novo confirmed to Fierce today that it's ending HERMES and ATHENA, two ziltivekimab studies in heart failure. Investigators were told Friday. The company says a monitoring committee recommended stopping because the studies were unlikely to succeed after July's ZEUS result. Novo still has a Phase 3 asset, but no longer has the same cardiovascular opportunity.

ZEUS helps explain why. Novo reported the expected reduction in inflammation markers, without a reduction in major cardiovascular events. The hazard ratio was 0.99, essentially no separation from placebo. The drug affected the biology it targeted, but the trial didn't establish the clinical benefit it was designed to test.

ZEUS enrolled people with atherosclerotic disease and chronic kidney disease, though. That isn't the same as a heart-failure trial. How far can we take that result?

It doesn't prove the other studies would fail. The committee judged their prospects too low to continue, according to Novo. HERMES tested cardiovascular deaths and serious heart-failure events. ATHENA tested symptoms and physical limitations over twelve months. Stopping both removes two different ways to build a heart-failure case. Their final results haven't been provided with this announcement.

That leaves ARTEMIS, which studies patients after an acute heart attack. Novo says it continues, with results expected in the first half of 2027. A pipeline slide that still says “Phase 3” could miss the change completely: the stage remains, while two paths to demonstrating patient benefit have stopped.

The remaining readout also has to answer a benefit-risk question. ZEUS reported more serious infections with ziltivekimab than placebo. Novo didn't give that as the reason for today's stops; it cited the low chance of success. When ARTEMIS reports, the size of any clinical benefit belongs beside the infection findings.

For competitive tracking, split the continuing post-heart-attack study from the stopped heart-failure work. Keep ARTEMIS on the watchlist; remove those stopped studies from the evidence you expect Novo to deliver. That is the change the development-stage label alone won't show.

ADARx filed for an IPO Friday as development spending accelerates. First-half R&D rose to about 48 million dollars, from 30 million a year earlier. It wants to fund a Phase 3 trial and precommercial work while advancing complement-disease programs and earlier assets. Preparing for a possible launch adds demands before the pivotal answer arrives.

The lead is onvuzosiran for hereditary angioedema. STOP-HAE is testing whether injections every three or six months can prevent attacks, with results expected by the end of 2027. Prevention and safety at those intervals are the clinical test behind the infrequent-dosing ambition.

I'd read the eventual offering terms against the milestones, not just the headline amount. How much supports the lead through its readout and precommercial work, and how much remains for the earlier pipeline? The offering size and allocations are still blank. Those numbers will show the funding plan behind the pipeline list.

Aptar Pharma and Aceso announced a development-services collaboration today. Aptar's Nanopharm business will develop the formulation and assess delivery devices for ACT-101, an inhaled antisense candidate for cystic fibrosis. No licensing rights or price were disclosed.

The work matters because ACT-101 is still preclinical. Aceso wants direct delivery to the lung, so the candidate needs a formulation and device that work together. A delivery specialist's involvement identifies who will tackle that problem. It doesn't tell us the problem has been solved.

Aptar is putting its expertise to work early in drug development, alongside its broader biologics-compatibility program. But for ACT-101, a selected formulation and delivery approach would tell us more about readiness for clinical testing than another partner logo. That's the next development milestone I'd track.

Novo's other announcement today moves semaglutide into a younger research population: children aged six to under twelve living with obesity. In STEP Young, roughly two in five receiving the drug moved below the obesity BMI threshold. That is a result people will repeat, so the meaning needs to travel with the number.

Novo reports 40.4 percent versus zero on placebo at 68 weeks, in an analysis assuming children stayed on their assigned treatment. The trial enrolled 165 children, and both groups received lifestyle support. Below the obesity threshold includes the overweight category. This is a change in BMI classification, not a claim that all those children reached normal weight.

The development significance is evidence in children younger than Wegovy's current US obesity indication. I wouldn't turn the category shift into a forecast for uptake. The size of the BMI benefit and whether children can stay on treatment matter to that assessment.

And those are precisely the details still missing. Novo says the primary BMI-change endpoint was met, but hasn't provided its numerical effect. The category shift is a secondary result supporting that main analysis. The company reports no new safety concerns, including growth or puberty; adverse-event and discontinuation rates aren't in this release. Detailed results are due at ObesityWeek in November.

The November read should connect three things: how much BMI changes, how many children stay on treatment, and what the growth data show.

With the age boundary kept clear. Wegovy injection's US obesity indication starts at twelve; safety and effectiveness for weight reduction are not established below twelve. Today's announcement doesn't extend that indication.

Quick note before our second story — if The Pharma Closeout is how you close out your pharma day, follow the show on Spotify or Apple Podcasts. SynAct is proposing another trial of resomelagon after two primary-endpoint misses in rheumatoid arthritis. I'd keep it on a partnering watchlist: the new proposal puts a specific explanation to a prospective test.

The history makes me cautious. Today's post-hoc ADVANCE analysis selects patients with more stable baseline CRP, a blood marker of inflammation. SynAct reports ACR20 responses, an arthritis improvement measure, of 79 percent versus 55 percent with placebo. Both groups received methotrexate. SynAct argues that temporary flares in other patients complicated the comparison. Improvement as a flare subsides could obscure the added drug's effect.

That makes the screening rule central. SynAct wants to establish baseline stability before randomization and extend treatment from twelve to 26 weeks. A partner could examine that design instead of relying on the subgroup headline.

Especially because EXPAND already produced a favorable post-hoc subgroup. ADVANCE enrolled patients with elevated inflammation, using a different dose and design, and still missed its primary endpoint. Today's release leaves material gaps: the stability rule, exact subgroup counts and statistical-adjustment details.

Then my watchlist is the full post-hoc analysis, a usable screening rule and FDA feedback. SynAct plans fourth-quarter discussions while considering licensing, an asset sale or a company sale. None is an announced agreement. The opportunity is to test the revised hypothesis; efficacy still has to be demonstrated.

Tomorrow, Roivant and Pulmovant present PHocus results for mosliciguat in pulmonary hypertension associated with interstitial lung disease. The European Respiratory Society presentation is at six-fifteen a.m. Eastern, followed by an investor call at eight.

The primary endpoint measures resistance to blood flow through the lung vessels at sixteen weeks. I'll read it alongside walking distance and safety. If resistance improves without a walking benefit, the trial could show a physiological effect while leaving improvement in patients' physical function unproven.

Have a good evening. Tomorrow's PHocus presentation gives us a chance to put that clinical question to actual results.

That's your Pharma Closeout: Novo remains in Phase 3 with two fewer paths to proving patient benefit. SynAct proposes a new test of an arthritis subgroup finding. Follow the show on Apple Podcasts, Spotify, or wherever you listen — a quick rating or share helps other listeners find us. Tomorrow's briefing lands on its own. ## Episode metadata — draft **Title:** Novo Ends Two More Ziltivekimab Heart-Failure Trials **Description:** Arriving late because of Monday's holiday, this September 7 edition covers Novo's HERMES and ATHENA shutdowns while ARTEMIS continues. We assess ADARx's proposed IPO, Aptar and Aceso's ACT-101 collaboration in cystic fibrosis, and Novo's STEP Young semaglutide results in childhood obesity. SynAct's resomelagon reanalysis raises the question of what another rheumatoid arthritis trial must establish after two primary misses. We also preview Roivant and Pulmovant's PHocus mosliciguat presentation in pulmonary hypertension associated with interstitial lung disease. **Tags:** Novo Nordisk, ziltivekimab, ADARx, cystic fibrosis, pediatric obesity, SynAct, mosliciguat ## Evidence notes — not spoken - **Novo stopping event:** [Fierce Biotech, September 7 — company confirmation](https://www.fiercebiotech.com/biotech/novos-blockbuster-hopes-ckd-program-dwindle-after-more-phase-3-trials-scrapped), corroborated by [Reuters, September 7 — company spokesperson](https://live.euronext.com/en/financial-news/novo-scraps-two-more-heart-drug-trials-further-dimming-growth-beyond-obesity). Bin approved this event-specific sourcing exception. ARTEMIS continuation and expected H1 2027 results come from the attributed company account. - **Trial questions:** [HERMES, NCT05636176](https://clinicaltrials.gov/study/NCT05636176): cardiovascular death, heart-failure hospitalization or urgent heart-failure visit. [ATHENA, NCT06200207](https://clinicaltrials.gov/study/NCT06200207): change in KCCQ clinical summary score at twelve months. The retrieved records predate the stopping announcement; used for design, not current status. - **ZEUS background:** [Novo, July 31](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916587): primary MACE HR 0.99, 95% CI 0.88–1.11; target engagement and reduced inflammation markers; more serious infections with ziltivekimab. No individual-component or class-wide failure inference. Commercial assessments in Alex's turns are editorial interpretation. - **ADARx:** [September 4 SEC S-1](https://www.sec.gov/Archives/edgar/data/1802369/000119312526383838/d903461ds1.htm), program summary, Use of Proceeds, STOP-HAE design and first-half R&D expense table. R&D was $48.319m versus $29.965m for the six months ended June 30, 2026 and 2025; rounded to about $48m/$30m on air. STOP-HAE tests 300mg every six months and 240mg every three months against placebo; topline expected by end-2027. No superiority to another active treatment or established dosing benefit is claimed. Precommercial work is a stated use; offering size and allocation fields are blank. [September 6 weekend coverage](https://www.fiercebiotech.com/biotech/abbvie-backed-adarx-plans-ipo-fund-array-clinical-stage-sirna-therapies) establishes the Monday intake context. - **Aptar–Aceso:** [Aptar, September 7](https://aptar.com/en-us/news-events/aptar-and-aceso-therapeutics-announce-collaboration-to-advance-inhaled-antisense-oligonucleotide-therapy-for-cystic-fibrosis): Nanopharm's formulation/device role and Aptar's broader biologics-compatibility work. [Aceso, March 22](https://www.aceso-therapeutics.com/satt-axlr-enters-the-capital-of-aceso-therapeutics-and-supports-the-development-of-act-101-for-cystic-fibrosis/) supplies dated preclinical context. No mutation-agnostic claim or undated mechanism detail; no future device order is asserted. - **STEP Young:** [Novo, September 7 first results](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916600). The 40.4%/0% category result uses the trial-product estimand; both arms had lifestyle intervention. Primary magnitude and numerical safety/discontinuation data are absent from this release. [Wegovy US prescribing information, revised June 2026](https://www.novo-pi.com/wegovy.pdf), sections 1 and 8.4, supplies the age/indication boundary. Sponsor safety statements are attributed. - **SynAct new analysis and plans:** [September 7 sponsor release](https://www.synactpharma.com/en/further-analysis-of-the-phase-2b-advance-study-reinforces-phase-2b-expand-results-and-supports-phase-3-development-fda-discussions-on-trial-design-planned-for-q4-2026/). Stable-baseline subgroup ACR20 79%/55% is post-hoc, not a confirmed responder population. The release does not operationally define stability or give exact subgroup counts and adjustment methods. Phase 3 duration and FDA discussions are proposals/plans. - **SynAct prior evidence:** [EXPAND primary report, September 4, 2023](https://www.synactpharma.com/en/synact-pharma-announces-top-line-data-from-the-12-week-expand-p2b-clinical-trial-in-severely-active-newly-diagnosed-rheumatoid-arthritis-patients/) reported ACR20 54.7% versus 55.7%, a primary miss. [February 22, 2024 EXPAND subgroup report](https://www.synactpharma.com/en/synact-pharma-announces-additional-data-from-the-expand-p2b-clinical-trial-supporting-continued-development-of-the-compound-in-rheumatoid-arthritis/) describes favorable post-hoc findings in early RA/elevated-CRP patients. [June 15, 2026 ADVANCE report](https://www.synactpharma.com/en/phase-2b-advance-study-demonstrates-positive-effects-of-resomelagon-in-rheumatoid-arthritis-supports-phase-3-design-regulatory-interactions-and-partnering/) documents high-inflammation eligibility and the missed primary DAS28-CRP comparison (per-protocol p=0.168). The studies differed in dose and design; this is not a claim that ADVANCE exactly replicated an EXPAND subgroup. - **PHocus watch:** [Roivant, September 6 schedule announcement](https://investor.roivant.com/news-releases/news-release-details/roivant-present-topline-results-phase-2-phocus-study-mosliciguat); [NCT06635850](https://clinicaltrials.gov/study/NCT06635850) for sixteen-week PVR and walking-distance endpoints. September 8 efficacy/safety results are excluded from this September 7 edition. ## Review boundary Stage 5 approved. Audio production and measured runtime are recorded in the separate Stage 6 production report. The earlier 13:55 map is an editorial planning budget, not measured runtime for this rewrite.