Natriuretic peptides are a family of cardiac hormones that act on one second-messenger system. Three therapeutic strategies have been built on it: a recombinant A-type peptide, a recombinant B-type peptide, and a small molecule that prevents the peptides being degraded. Only the last holds a UK marketing authorisation.
The biology
Atrial natriuretic peptide (ANP) is a 28-amino-acid peptide released from atrial myocytes in response to wall stretch. B-type natriuretic peptide (BNP) is a 32-residue peptide released mainly from the ventricle under the same stimulus. Both act on the particulate guanylyl cyclase receptors NPR-A and NPR-B, raising intracellular cyclic guanosine monophosphate (cGMP). The downstream effects are natriuresis, diuresis, vasodilation and suppression of the renin–angiotensin–aldosterone system. The peptides are cleared by neprilysin (neutral endopeptidase) and by the clearance receptor NPR-C.
Three routes into the same pathway
Recombinant ANP — carperitide. Carperitide is a recombinant form of alpha-human ANP (28 residues). It has been approved in Japan since 1995 for acute heart failure and has never held a US or European marketing authorisation. The outcome literature is not settled: a Japanese registry analysis reported an association between carperitide use and higher in-hospital mortality, while a later observational study reported a more favourable signal at low dose. The evidence is contradictory, and it is observational.
Recombinant BNP — nesiritide. Nesiritide, a recombinant human BNP, was approved in the United States in 2001 on the strength of small haemodynamic and symptom studies. The ASCEND-HF trial subsequently found no effect on the composite of death or heart-failure hospitalisation at 30 days, with a mild improvement in dyspnoea and a higher incidence of hypotension. It holds no UK marketing authorisation.
Neprilysin inhibition — sacubitril/valsartan. The one UK-licensed route into this system is indirect. Sacubitril is a prodrug whose active metabolite inhibits neprilysin, the enzyme that degrades natriuretic peptides; valsartan blocks the angiotensin II type-1 receptor. The combination holds a UK marketing authorisation for symptomatic chronic heart failure with reduced ejection fraction and is the subject of NICE technology appraisal TA388. The licensed mechanism raises endogenous peptides rather than supplying a peptide drug.
The UK position
No natriuretic peptide analogue holds a UK marketing authorisation. Carperitide's approval is Japan-only. Under the Medicines Act 1968 and the Human Medicines Regulations 2012, a peptide offered for supply in the UK without a marketing authorisation is an unlicensed medicine, and material sold as research use only is not a medicine at all — it carries no assurance of identity, purity, sterility or endotoxin content. This article describes the research record; it is not clinical guidance and contains no dosing information.
Evidence grade and how to read it
The physiology of the natriuretic peptide system is well established and substantially uncontested. The therapeutic performance of the recombinant peptides is the weakest part of the story: acute haemodynamic effects are reproducible, but hard clinical outcomes have not followed, and the most rigorous trial in the class was neutral. Evidence grade for the recombinant peptide drugs: Limited to Moderate, depending on endpoint. That distinction — mechanism settled, outcome benefit not — is the one to carry forward.
This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.