Scenesse (afamelanotide) / Clinuvel - LARVOL DELTA

Treatment Advances in Vitiligo: An Updated Review. (PubMed, Dermatol Pract Concept) - "The advent of treatment modalities like Janus kinase inhibitors, prostaglandin analogues, antioxidants, TNF-α inhibitors, targeted phototherapy, and excimer lasers has revolutionized the therapeutic possibilities, offering a ray of hope to the individuals suffering from this devastating condition."

Journal • Review • Dermatology • Immunology • Inflammation • Vitiligo

German Cohort Observational Study to Investigate the Short- and Long-Term Safety and Clinical Effectiveness of Afamelanotide 16 mg (SCENESSE) in Patients With Erythropoietic Protoporphyria (EPP). (PubMed, Photodermatol Photoimmunol Photomed) - "Afamelanotide treatment was highly effective and associated with a higher QoL in EPP patients. The study shows a positive safety profile of afamelanotide, with the treatment providing an ongoing clinical benefit."

Journal • Observational data • Genetic Disorders • Hematological Disorders • Metabolic Disorders

A Study to Compare the Efficacy and Safety of SCENESSE and Narrow-Band Ultraviolet (NB-UVB) Light Versus NB-UVB Light Alone in Patients with Vitiligo (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Clinuvel, Inc. | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Dermatology • Immunology • Vitiligo

Pharmacokinetics of Afamelanotide in EPP Patients (clinicaltrials.gov) - P1/2 | N=28 | Completed | Sponsor: Clinuvel Europe Limited | Recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Jan 2025 | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Metabolic Disorders

Discovery of MT-7117 (Dersimelagon Phosphoric Acid): A Novel, Potent, Selective, and Nonpeptidic Orally Available Melanocortin 1 Receptor Agonist. (PubMed, J Med Chem) - "Afamelanotide, an α-melanocyte-stimulating hormone (α-MSH) analogue MC1R agonist, is used clinically for treating erythropoietic protoporphyria (EPP) as a subcutaneous implant formulation. Compound 11 is currently in clinical trials for the treatment of EPP, X-linked protoporphyria (XLP), and systemic sclerosis (SSc). Proof of concept was obtained in phase 2 clinical studies on EPP and XLP."

Journal • Fibrosis • Genetic Disorders • Immunology • Metabolic Disorders • Scleroderma • Systemic Sclerosis

Evaluating the Importance of Patient Input in NICE Highly Specialized Technology (HST) Assessments: Insights From Review Reports (ISPOR-EU 2024) - "In some assessments, patient input was mentioned more than 20 times (e.g., Selumetinib, Afamelanotide, Onasemnogene abeparvovec)... NICE reports show a significant number of mentions of patient input and some acknowledgements. In some reports, patient feedback highlighted new or additional topics for consideration."

Clinical • NICE • Review

Mechanistic Model for Drug Release from PLGA-Based Biodegradable Implants for In Vitro Release Testing: Development and Validation. (PubMed, ACS Appl Bio Mater) - "The model has been validated using in vitro release data obtained from implants of four drugs (buserelin, afamelanotide, brimonidine, and nafarelin). The model presented in this manuscript provides valuable insights into the kinetics and mechanism of drug release from PLGA-based solid implants and has demonstrated the potential for optimizing formulation design. The in vitro release model, coupled with physiologically based pharmacokinetic (PBPK) modeling, can predict the in vivo performance of implants and can be used to support bioequivalence studies in a drug development program."

Journal • Preclinical

The impact of minimal sunlight exposure on bone health: insights from a cohort study in erythropoietic protoporphyria. (PubMed, J Clin Endocrinol Metab) - "25-hydroxyvitamin D (25(OH)D) status plays a crucial role in both preventing low BMD and improving BMD. EPP is a natural model for lack of sunlight exposure and vitamin D deficiency, underlining the importance of lifelong adequate vitamin D status for bone health in the general population."

Journal • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Pain • Rheumatology

Topline results of the AURORA Trial: A phase 2, randomized, double-blind, placebo-controlled trial of bitopertin in erythropoietic protoporphyria (EADV 2024) - P2 | "Exclusion criteria included concurrent treatment with afamelanotide or dersimelagon. Bitopertin has been shown to significantly reduce PPIX levels in prior clinical and nonclinical studies of EPP. The AURORA trial evaluates whether reductions in PPIX with bitopertin can improve measures of light tolerance in adults with EPP. Topline safety and efficacy data will be presented."

Clinical • P2 data • Bone Marrow Transplantation • Genetic Disorders • Hepatology • Metabolic Disorders • Pain

Topline Results of the AURORA Trial: A Phase 2, Randomized, Double-blind, Placebo-controlled Trial of Bitopertin in Erythropoietic Protoporphyria (EADV 2024) - P2 | "Exclusion criteria included concurrent treatment with afamelanotide or dersimelagon. Bitopertin has been shown to significantly reduce PPIX levels in prior clinical and nonclinical studies of EPP. The AURORA trial evaluates whether reductions in PPIX with bitopertin can improve measures of light tolerance in adults with EPP. Topline safety and efficacy data will be presented."

Clinical • P2 data • Bone Marrow Transplantation • Genetic Disorders • Hepatology • Metabolic Disorders • Pain

A systematic review of case series and clinical trials investigating systemic oral or injectable therapies for the treatment of vitiligo (EADV 2024) - "Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness."

Clinical • Review • Dermatology • Immunology • Vitiligo

The effects of afamelanotide on UVR-induced DNA damage, acute inflammatory and DNA repair responses in human skin (ESDR 2024) - "In UVR-irradiated epidermis, afamelanotide significantly reduced DNA-damage markers gH2AX (at 24h) and CPD (all timepoints) (p<0.01). Hence, besides promoting melanogenesis, afamelanotide reduced the magnitude of UVR-induced DNA damage, as well as pro-inflammatory and DNA damage-repair/oxidative stress responses in human skin, indicating its potential in treatment of UVR related skin disorders."

Dermatology • IL1A • PMEL

Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management. (PubMed, Liver Int) - "Depending on the severity of the liver disease, phlebotomies, exchange transfusions and ultimately liver transplantation with subsequent haematopoietic stem cell transplantation (HSCT) are therapeutic options, whereby multidisciplinary management including porphyria experts is mandatory. Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life."

Journal • Review • Bone Marrow Transplantation • Cholestasis • Gastroenterology • Genetic Disorders • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Pain • Transplantation

The effects of afamelanotide on ultraviolet radiation-induced acute inflammatory and DNA repair responses in healthy human skin (BAD 2024) - "Transcriptomic analysis also demonstrated that, through comparison of skin under the same irradiation conditions, intervention with afamelanotide significantly upregulated premelanosome protein (PMEL gene), which plays a role in the synthesis of melanosomes. In conclusion, in addition to promoting melanogenesis, in this study afamelanotide reduced the magnitude of UVR-induced proinflammatory and DNA damage repair and oxidative stress responses in human skin, indicating its potential broad, innovative scope in treatment of UVR-induced skin disorders."

Clinical • IO biomarker • Dermatology • Oncology • IFNG • PMEL • TLR3

When the diagnosis is written in the DNA: a case of erythropoietic protoporphyria in a patient with a chromosome-18 deletion. (PubMed, Dermatol Reports) - "Furthermore, a genetic analysis identified an intronic variant on one allele, c.315-48T>C (IVS3-48T>C), which is categorized as a susceptibility polymorphism, and a complete deletion of the ferrochelatase gene on the other allele. The patient's clinical condition improved following the June 2022 afamelanotide implant procedure."

Journal • Dermatology • Genetic Disorders • Metabolic Disorders

Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort. (PubMed, Life (Basel)) - "This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function."

HEOR • Journal • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Rare Diseases

TOPLINE RESULTS OF THE AURORA TRIAL: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF BITOPERTIN IN ERYTHROPOIETIC PROTOPORPHYRIA (EHA 2024) - P2 | "Exclusion criteria included alanine aminotransferase/aspartate aminotransferase values ≥2x theupper limit of normal, hemoglobin <10 g/dL, or concurrent treatment with afamelanotide or dersimelagon. Bitopertin has been shown to significantly reduce PPIX levels in prior clinical andnonclinical studies of EPP. The AURORA trial evaluates whether reductions in PPIX with bitopertin can improvemeasures of light tolerance in adults with EPP. Topline safety and efficacy data will be presented."

Clinical • P2 data • Bone Marrow Transplantation • Cholestasis • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Pain • Transplantation

Fair Funding Decisions: Consistency of the Time Horizons Used in the Calculation of Quality-Adjusted Life Years for Therapies for Very Rare Diseases by the National Institute for Health and Care Excellence in England. (PubMed, Int J Environ Res Public Health) - "In contrast, for the only technology with a final negative funding decision, i.e., afamelanotide for treating the lifelong chronic disease erythropoietic protoporphyria, a time horizon that was shorter than the expected treatment duration was used. The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE should be reviewed."

HEOR • Journal • Reimbursement • US reimbursement • Genetic Disorders • Metabolic Disorders • Rare Diseases

Afamelanotide in protoporphyria and other skin diseases: a review. (PubMed, Postepy Dermatol Alergol) - "The positive effect of afamelanotide in EPP administered subcutaneously improved tolerance to artificial white light and increased pain-free time spent in direct sunlight. In this review we summarize the possible use of afamelanotide in dermatology, with special emphasis on EPP and encourage including afamelanotide as a treatment option in patient care."

Journal • Review • Dermatology • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Pain • Rare Diseases

Vitamin D status in EPP patients taking the systemic photoprotective agent afamelanotide. (PubMed, Br J Dermatol) - No abstract available

Journal

Pharmacokinetics of Afamelanotide in EPP Patients (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Clinuvel Europe Limited

New P1/2 trial • Genetic Disorders • Metabolic Disorders

The effects of cholecalciferol and afamelanotide on vitamin D levels in erythropoietic protoporphyria; a multicentre cohort study. (PubMed, Br J Dermatol) - "Cholecalciferol remains essential for treatment of vitamin D deficiency in EPP, irrespective of new treatment options like afamelanotide. Afamelanotide treatment did not affect vitamin D levels. We suggest that future guidelines include continuous monitoring of vitamin D and prescription of cholecalciferol in all patients with EPP, including those treated with afamelanotide."

Journal • Genetic Disorders • Metabolic Disorders • Osteoporosis • Pain • Rheumatology

Does NICE Give Any Importance to Patient Input: Insights from Review of NICE Highly Specialized Technology (HST) Assessment Reports (ISPOR 2024) - "In some assessments, patient input was mentioned 20+ times (e.g. Selumetinib, Afamelanotide, Onasemnogene abeparvovec)... NICE reports show a significant number of mentions of patient input and some acknowledgements. In some reports, patient feedback highlighted new/additional topics for consideration."

Clinical • NICE • Review • Transplantation

A systematic review of case series and clinical trials investigating systemic oral or injectable therapies for the treatment of vitiligo. (PubMed, Skin Res Technol) - "Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness."

Journal • Review • Dermatology • Immunology • Vitiligo

Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP) (clinicaltrials.gov) - P2 | N=6 | Completed | Sponsor: Clinuvel (UK) Ltd. | Active, not recruiting ➔ Completed | Phase classification: P2a ➔ P2

Phase classification • Trial completion • Dermatology • Genetic Disorders • Hematological Disorders • Metabolic Disorders