Four this week: plaque that shrank, a trial BP shot, swallowing gene therapy

Lowering LDL cholesterol further shrank coronary plaque more over 18 months in a Danish trial

On 30 October 2026, JAMA Cardiology published prespecified imaging analyses of FLOWPROMOTE, a multicentre randomised trial in Denmark. It enrolled 104 people with newly diagnosed stable coronary artery disease who had never taken a statin; their average age was 64, and 79% were men. Half were assigned to atorvastatin alone, the other half to a stronger combination of rosuvastatin and ezetimibe, for 18 months. Coronary CT angiography measured plaque across the whole coronary tree at the start, at 9 months and at 18 months.

LDL cholesterol fell from 119.7 to 69.5 mg/dL (about 3.1 to 1.8 mmol/L, −38%) on atorvastatin and from 127.4 to 42.5 mg/dL (about 3.3 to 1.1 mmol/L, −65%) on the combination. At 18 months total plaque volume had shrunk by 21.1% with the combination and by 13.6% with atorvastatin (difference −30.9 mm³; 95% CI −57.2 to −4.5), and the soft, noncalcified part by 28.2% versus 20.0%. Calcified plaque grew by a similar amount in both groups. Total plaque shrank in 47 of 52 people on the combination and in 38 of 51 on atorvastatin, and the lower the LDL a person reached, the more plaque regressed.

Plaque volume on a scan is a marker, not an outcome: these analyses were secondary end points in about a hundred people, and they do not show fewer heart attacks or deaths. The two arms also differed in both the statin and the added ezetimibe, so the result cannot say which change mattered more. Earlier imaging studies, mostly with intravascular ultrasound, had shown modest plaque regression with lipid-lowering therapy; this trial measured the whole coronary tree in people starting treatment.

A single injection of an experimental gene-silencing drug cut angiotensinogen by up to 93% in a phase 1 trial

Also on 30 October, JAMA Cardiology published the first human trial of ART101, an investigational small interfering RNA (siRNA) from Arnatar Therapeutics. Conjugated to N-acetylgalactosamine, which directs it to the liver, it targets angiotensinogen, the precursor of the angiotensin peptides and a key driver of the renin-angiotensin-aldosterone system that regulates blood pressure. The study ran at Beijing Friendship Hospital: 40 healthy adults were randomised 6 to 2 to a single injection of the drug at one of several dose levels or to placebo, and 8 people with hypertension received the highest dose openly; everyone was followed for 24 weeks.

At the highest dose, angiotensinogen in the blood fell by up to 93% on average in healthy volunteers and by 90% in people with hypertension. Twenty-four weeks after that single injection, 24-hour ambulatory systolic pressure in healthy participants was 12.9 mm Hg lower than with placebo. Adverse events occurred in 76.7% of those on the drug and 70.0% on placebo, all mild to moderate; there were no serious adverse events, injection-site reactions or high potassium levels.

This was a phase 1 trial whose main question was safety. The blood pressure readings were exploratory, the placebo-corrected figure came from healthy volunteers, and only eight people with hypertension took part, without a placebo group. Several authors are employees of the developer. The drug is not approved anywhere and still has to be tested in larger trials in people with high blood pressure.

In type 1 diabetes with excess weight, an experimental GLP-1/GIP drug lowered weight by up to 6.7% in 16 weeks

On 28 October, Diabetes Care published a phase 2 double-blind, placebo-controlled trial of acmopatide (CT-868), an investigational injectable drug that acts on the GLP-1 and GIP receptors. It included 111 adults with type 1 diabetes, HbA1c between 7.0% and 10.0% and a body mass index of 27 or more, who were randomised to one of three doses of acmopatide or placebo for 16 weeks.

HbA1c fell by 0.4 to 0.6 percentage points on acmopatide and by 0.3 on placebo; for the middle dose the difference from placebo was −0.3 points (90% CI −0.6 to −0.1), significant only nominally. An HbA1c below 7.0% was reached by 55.6% of people on that dose and 33.3% on placebo. Body weight changed by −3.3% to −6.7% on acmopatide and by +0.3% on placebo, and on the two higher doses the daily insulin dose fell 3.4% to 14.9% more than on placebo. There was no diabetic ketoacidosis and no severe hypoglycaemia; side effects were mostly gastrointestinal.

The trial was short, with about 27 to 29 people per group, and the glucose effect was modest; it does not show effects on diabetes complications. The sponsor listed in the trial registry is Carmot Therapeutics. Acmopatide remains investigational, and larger and longer trials would be needed to tell whether it has a place alongside insulin.

A one-time gene therapy injected into throat muscles improved swallowing in all nine patients with a rare inherited muscle disease, the company reports

On 28 October, Benitec Biopharma reported interim results from the first-in-human phase 1b/2a study of BB-301 in oculopharyngeal muscular dystrophy (OPMD), a rare inherited disease caused by a mutation in the PABPN1 gene that weakens the throat muscles. According to the company, progressive difficulty swallowing affects 97% of patients and can lead to choking, malnutrition and aspiration pneumonia, and there is no approved treatment.

BB-301 is an AAV9-based vector that carries two small RNAs to silence the faulty PABPN1 gene together with a working copy of it, an approach the company calls "silence and replace". It is given once, by injection directly into the muscles that drive swallowing. Six patients on the lower dose have been followed for 12 months, and three on the higher dose for 3 to 9 months. All nine met the study's criteria for response. At 3 months, clearing of food and liquid from the throat on X-ray video of swallowing improved in 4 of 6 patients on the lower dose and 3 of 3 on the higher dose, and swallowing capacity on a timed cold-water drinking test in 1 of 6 and 2 of 3. No serious adverse events have been reported.

These are nine people in an open-label study without a control group, described in a company press release and a congress poster rather than a peer-reviewed paper, and "response" is defined by the study's own criteria. The FDA's Fast Track and orphan drug designations are not an approval. The company plans a pivotal study in mid-2027.

This material is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.

Sources

• Mortensen MB, Iraqi N, Sand NPR, et al. Intensive vs More Intensive Lipid-Lowering Therapy and Plaque Regression in Statin-Naive Patients: Prespecified Analyses From the FLOWPROMOTE Randomized Clinical Trial. JAMA Cardiol. 2026. PMID 42961412, doi:10.1001/jamacardio.2026.4788, NCT04737408

• Zhang J, et al. N-Acetylgalactosamine-Conjugated Small Interfering RNA Targeting Hepatic Angiotensinogen in Hypertension: A Phase I Clinical Trial With Randomized Part A and Open-Label Part B. JAMA Cardiol. 2026. PMID 42961436, doi:10.1001/jamacardio.2026.4936

• Klein KR, et al. A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Acmopatide (CT-868), a Fully Biased GLP-1/GIP Receptor Agonist, in Adults With Type 1 Diabetes and Overweight or Obesity. Diabetes Care. 2026. PMID 42949535, doi:10.2337/dc26-1059, NCT06062069

• Benitec Biopharma. Positive interim Phase 1b/2a results for high dose BB-301 and continued durable improvements for low dose BB-301. Press release, 28 October 2026. GlobeNewswire, NCT06185673