dersimelagon (MT-7117) / Tanabe Pharma, LEO Pharma - LARVOL DELTA

LEO Pharma Announces FDA Acceptance of Dersimelagon NDA with Priority Review and Closes Acquisition from Tanabe Pharma (Businesswire) - "The U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for dersimelagon for filing and granted it Priority Review, with a Prescription Drug User Fee Act (PDUFA) date expected by the end of February 2027."

FDA filing • PDUFA • Priority review • Genetic Disorders

Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP) (clinicaltrials.gov) - P3 | N=286 | Active, not recruiting | Sponsor: Tanabe Pharma America, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Metabolic Disorders

Biological response in dermal fibroblasts predicts skin clinical response: Lessons from the MT-7117 Phase 2 Systemic Sclerosis clinical trial (ACR Convergence 2026) - No abstract available

Clinical • P2 data • Immunology • Scleroderma • Systemic Sclerosis

INSPIRE: INcreased Sun Exposure Without Pain In Research Participants With EPP or XLP (clinicaltrials.gov) - P3 | N=165 | Completed | Sponsor: Tanabe Pharma America, Inc. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Metabolic Disorders • Pain

Efficacy and Safety of Dersimelagon in Adults and Adolescents with Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP): Top-line Results from the INSPIRE Phase 3 Randomized Clinical trial (AAD 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • P3 data: top line • Genetic Disorders • Metabolic Disorders

New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin. (PubMed, Expert Opin Pharmacother) - "However, safety and efficacy of dersimelagon and bitopertin need to be further characterized. Moreover, to ensure benefit for patients and access to therapy after regulatory approval, it also would be important to generate data on the relative safety and efficacy as compared to afamelanotide."

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

Endocrine modulation of inflammation: the role of adrenocorticotropic hormone and cortisol. (PubMed, Endocr Pract) - "Adrenocorticotropic hormone (ACTH), via the hypothalamic-pituitary-adrenal axis and direct interaction with MCR2, stimulates both cortisol synthesis and mediates steroid-independent immunomodulation in extra-adrenal tissues. Recent preclinical studies of selective MCR agonists, including MCR1-targeted compounds like dersimelagon, highlight novel therapeutic possibilities for autoimmune and fibrotic disorders. Understanding the dual steroidogenic and non-steroidogenic actions of melanocortins provides a framework for developing targeted therapies with improved safety profiles compared with conventional glucocorticoids."

Journal • Review • Fibrosis • Immunology • Inflammation • POMC-null Obesity

New pharmacotherapies for the erythropoietic protoporphyrias: an analysis of trial protocols from a patient perspective. (PubMed, Orphanet J Rare Dis) - No abstract available

Journal • Genetic Disorders • Metabolic Disorders • Rare Diseases

Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases. (PubMed, Diseases) - "Among them, α-MSH analogs play a role in atopic dermatitis and scleroderma, and MC1R agonist Dersimelagon has shown effectiveness in systemic sclerosis. The FDA has recently approved the repository corticotropin injection (RCI) to treat sarcoidosis. The FDA has also approved various melanocortin agonists, i.e., Bremelanotide, Afamelanotide, and Setmelanotide, for the treatment of hypoactive sexual desire disorder, Erythropoietic protoporphyria, and obesity, due to pro-opiomelanocortin and leptin receptor deficiency, respectively. Therefore, this review aims to summarize the function and genetic polymorphism of melanocortin receptors, regulatory pathways involving MCRs, and the existing evidence of the prime effect of MCRs on inflammatory responses via different mechanisms and their potential therapeutic use in inflammatory diseases."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Atopic Dermatitis • CNS Disorders • Depression • Dermatitis • Dermatology • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Major Depressive Disorder • Melanoma • Metabolic Disorders • Multiple Sclerosis • Obesity • Ocular Inflammation • Oncology • Ophthalmology • POMC-null Obesity • Psychiatry • Reperfusion Injury • Respiratory Diseases • Rheumatology • Sarcoidosis • Scleroderma • Sexual Disorders • Solid Tumor • Systemic Sclerosis • Type 2 Diabetes Mellitus • Uveitis • LEP • LEPR

The Purpose of This Study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Mitsubishi Tanabe Pharma Corporation | Active, not recruiting ➔ Completed

Trial completion

The Purpose of This Study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Mitsubishi Tanabe Pharma Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed

The Purpose of This Study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Mitsubishi Tanabe Pharma Corporation | Not yet recruiting ➔ Recruiting

Enrollment open

The Purpose of This Study is to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects. (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Mitsubishi Tanabe Pharma Corporation

New P1 trial

INSPIRE: INcreased Sun Exposure Without Pain In Research Participants With EPP or XLP (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Mitsubishi Tanabe Pharma America Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Metabolic Disorders • Pain

Assessment of Potential Drug-Drug Interactions for Novel Oral Melanocortin-1 Receptor Agonist Dersimelagon. (PubMed, Pharmacol Res Perspect) - P1, P2, P3 | "The impact of 300-mg dersimelagon on the pharmacokinetics (PK) of substrate drugs and the effect of co-administering verapamil on 100-mg dersimelagon PK (as substrate drug) were investigated in healthy participants in a Phase 1 study...Midazolam (CYP3A substrate), digoxin (P-gp), pravastatin (OATP), and simvastatin (CYP3A) did not show any clinically relevant DDI effects when co-administered with dersimelagon...Dersimelagon 300 mg did not elicit major DDIs involving CYP/UGT enzymes and drug transporters; however, dersimelagon may have potential for clinically relevant DDIs with drugs that are substrates for BCRP, such as atorvastatin and rosuvastatin, and caution should be exercised when co-administering 300-mg dersimelagon with these statin drugs. Trial Registration: ClinicalTrials.gov: NCT04793295, NCT04402489, NCT04440592, NCT02834442, NCT03520036, NCT03503266."

Clinical • Journal • CYP2C9

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

Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects With Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP) (clinicaltrials.gov) - P3 | N=301 | Recruiting | Sponsor: Mitsubishi Tanabe Pharma America Inc. | Active, not recruiting ➔ Recruiting | N=151 ➔ 301 | Trial completion date: Jun 2025 ➔ Dec 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2027

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Genetic Disorders • Metabolic Disorders

Physiologically based pharmacokinetic modelling to predict potential drug-drug interactions of dersimelagon (MT-7117). (PubMed, Br J Clin Pharmacol) - "Overall, PBPK modelling results indicate that the simulated changes in plasma exposure of atorvastatin and rosuvastatin following coadministration with dersimelagon 100 or 200 mg are not clinically significant, but caution and appropriate clinical monitoring should be recommended."

Journal • PK/PD data • Breast Cancer • Genetic Disorders • Metabolic Disorders • Oncology • Solid Tumor

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

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

BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS IN SUBJECTS WITH ILD IN A PHASE 2 STUDY TO EVALUATE EFFICACY, SAFETY, AND TOLERABILITY OF MT-7117 IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (EULAR 2024) - P2 | "Randomized subjects (SSc-ILD+ and SSc-ILD-) were homogenous in demographics, baseline mRSS, ppFVC%, and concomitant IS. A large percentage of patients were not assessed for ILD and ILD may be missed in early dcSSc (Khanna D, Denton CP, 2021). The topline data of MT-7117 G02 will be available early 2024 and will assess the efficacy of MT-7117 to prevent disease progression in the subjects with SSc ILD+ and SSc-ILD-."

Clinical • P2 data • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Effect of Hepatic and Renal Impairment on the Pharmacokinetics of Dersimelagon (MT-7117), an Oral Melanocortin-1 Receptor Agonist. (PubMed, Clin Pharmacol Drug Dev) - P1 | "Maximum observed plasma concentration and area under the plasma concentration-time curve from time 0 extrapolated to infinity were similar with moderate renal impairment but higher with mild (1.86- and 1.87-fold higher, respectively) and severe (1.17- and 1.45-fold higher, respectively) renal impairment versus normal renal function. Dersimelagon was generally well tolerated."

Journal • PK/PD data • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Renal Disease • Scleroderma • Systemic Sclerosis

Illuminating Dersimelagon: A Novel Agent in the Treatment of Erythropoietic Protoporphyria and X-Linked Protoporphyria. (PubMed, Pharmaceuticals (Basel)) - "However, the emergence of innovative therapies, such as dersimelagon, is reshaping the therapeutic landscape for these conditions. In this review, we summarize salient features of the properties of dersimelagon, shedding light on its potential role in advancing our understanding of treatment options for EPP and XLP."

Journal • Review • Genetic Disorders • Metabolic Disorders

BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS IN A PHASE 2 STUDY TO EVALUATE EFFICACY, SAFETY, AND TOLERABILITY OF MT-7117 IN SUBJECTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS (SSWC 2024) - P2 | "The study included subjects with dcSSc, age >= 18 years and a disease duration <= 5 years who were on a stable standard of care treatment and receiving one stable concomitant immunosuppressant (Mycophenolate/Mycophenolic acid [MMF], Methotrexate [MTX], Hydroxychloroquine [HCQ], or Azathioprine [AZA]). There were no major imbalances in the baseline demographics or in the percentage on immunosuppressants among the three regions, although some variation in SSc autoantibody specificity were observed."

Clinical • P2 data • Fibrosis • Immunology • Inflammation • Rheumatology • Scleroderma • Systemic Sclerosis