Skin Peptides

Difelikefalin (Korsuva in the U.S., Kapruvia in Europe) is a synthetic tetrapeptide built entirely from D-amino acids - D-Phe-D-Phe-D-Leu-D-Lys capped with a 4-aminopiperidine-4-carboxylic acid - that acts as a selective agonist at the kappa opioid receptor. Its defining property is what it cannot do: the molecule is hydrophilic and bulky enough that it does not meaningfully cross the blood-brain barrier, so it reaches kappa receptors on peripheral sensory nerve endings, keratinocytes and immune cells while leaving the central kappa receptors that produce dysphoria and hallucinations largely untouched. It has no activity at the mu opioid receptor, so it carries neither euphoria nor respiratory depression. In the Phase 3 KALM-1 and KALM-2 trials in hemodialysis patients with moderate-to-severe chronic-kidney-disease-associated pruritus, roughly 40-51% of difelikefalin-treated patients achieved a clinically meaningful (>=3-point) reduction on the 10-point Worst Itching Intensity NRS at 12 weeks versus roughly 20-28% on placebo. The FDA approved intravenous difelikefalin in August 2021; the EU approved it as Kapruvia in April 2022.

A senolytic peptide designed to selectively clear senescent cells by disrupting FOXO4-p53 interaction.

A naturally occurring copper-binding peptide studied for skin regeneration, wound healing, and anti-aging effects.

A multi-peptide blend of BPC-157, TB-500, and GHK-Cu formulated for tissue repair and skin rejuvenation.

The first FDA-approved targeted oral macrocyclic peptide — an IL-23 receptor antagonist for moderate-to-severe plaque psoriasis, marking a new era for oral peptide therapeutics.

A multi-peptide blend combining BPC-157, TB-500, GHK-Cu, and KPV for comprehensive tissue repair and anti-inflammatory support.

A tripeptide derived from alpha-MSH, studied for anti-inflammatory and gut-protective properties.

A human antimicrobial peptide studied for innate immunity, wound healing, and biofilm disruption.

A melanocortin receptor agonist FDA-approved (in Europe) for preventing phototoxicity in erythropoietic protoporphyria.

A cosmetic peptide studied for reducing the appearance of wrinkles by modulating muscle contraction signaling.

Barzolvolimab (development code CDX-0159) is an investigational humanized IgG1 monoclonal antibody from Celldex Therapeutics that works by a mechanism new to allergy and dermatology: it depletes mast cells. It binds with high specificity to the KIT receptor (CD117), a receptor tyrosine kinase that mast cells depend on for their growth, survival and activation, and blocks KIT from being switched on by its natural ligand, stem cell factor (SCF). Because mast cells cannot survive without KIT signaling, blocking the receptor lowers mast-cell numbers throughout the body - an effect visible as a dose-dependent fall in blood tryptase (a mast-cell marker) and a drop in mast cells in the skin. Mast cells are the central drivers of chronic urticaria (chronic hives): when they release histamine and other mediators they cause the wheals, angioedema and itch that define the disease, so removing the cells themselves is a more upstream approach than blocking a single downstream signal. Barzolvolimab's lead program is chronic spontaneous urticaria (CSU) that no longer responds to antihistamines, where it is being tested in two large replicate Phase 3 trials, EMBARQ-CSU1 and EMBARQ-CSU2, which together enrolled 1,939 patients - the largest Phase 3 program ever run in antihistamine-refractory CSU - with topline results expected in late 2026 and a planned regulatory (BLA) filing in 2027. It has also shown strong Phase 2 results in the chronic inducible urticarias - cold urticaria and symptomatic dermographism - and is being explored in prurigo nodularis, atopic dermatitis and eosinophilic esophagitis. Barzolvolimab is an investigational biologic given by subcutaneous injection under clinical-trial or specialist supervision; it is not approved, and it is not a supplement, nootropic or research chemical.

Amlitelimab (SAR445229, formerly KY1005) is a fully human, non-T-cell-depleting monoclonal antibody from Sanofi that blocks OX40 ligand (OX40L), a costimulatory signal that drives and sustains T-cell-mediated inflammation. Rather than neutralizing a single cytokine like IL-4/IL-13 (dupilumab) or IL-5 (depemokimab), amlitelimab acts upstream at the OX40-OX40L checkpoint to dampen a broad, memory-driven inflammatory program without depleting T cells. Its lead (anchor) indication is moderate-to-severe atopic dermatitis in people aged 12 and older, where a distinctive feature is very infrequent dosing: after a loading dose it is given subcutaneously as little as four times a year (every 12 weeks). In the Phase 3 program - COAST 1, COAST 2 and SHORE - amlitelimab met its primary endpoints with EASI-75 and vIGA-AD 0/1 responses that increased over time, though COAST 2's absolute response rates were more modest and some observers called that readout mixed. Amlitelimab is investigational and not yet approved by any regulator; Sanofi originally gained it through its ~$1.1B acquisition of Kymab in 2021.

Rocatinlimab (AMG 451 / KHK4083) is an investigational anti-OX40 monoclonal antibody developed by Kyowa Kirin and Amgen for moderate-to-severe atopic dermatitis (eczema). Unlike amlitelimab, which blocks the OX40 ligand (OX40L) on antigen-presenting cells without depleting cells, rocatinlimab binds the OX40 receptor directly on activated pathogenic T cells and reduces (depletes) them - a 'T-cell rebalancing' approach meant to reset the immune drivers of chronic inflammation rather than continuously neutralize a single cytokine. In the large Phase 3 ROCKET program the drug met its co-primary endpoints: in ROCKET-IGNITE (NCT05398445; 769 adults, added to topical therapy) week-24 EASI-75 reached about 42% (higher dose) and 36% (lower dose) versus roughly 13% on placebo, and vIGA-AD 0/1 reached about 24% and 19%; in the ROCKET-HORIZON monotherapy study (NCT05651711) EASI-75 was about 33% versus 14% on placebo, though the drug showed no superiority over dupilumab. The pooled Phase 3 results were published in The Lancet in 2025. Despite hitting its endpoints, the program then unraveled on two fronts: in January 2026 Amgen ended the collaboration on strategic-portfolio grounds and returned global rights to Kyowa Kirin, and on March 3, 2026 Kyowa Kirin discontinued ALL rocatinlimab clinical trials - across atopic dermatitis, prurigo nodularis and uncontrolled asthma - after a safety review identified cases of Kaposi's sarcoma (one newly confirmed and one suspected, in addition to a previously confirmed case) that suggested a possible mechanistic link to OX40-pathway modulation. Rocatinlimab is investigational, was never approved by any regulator, and its clinical development has been halted.