Sentinel (cenegermin-bkbj) / Dompe - LARVOL DELTA

Systematic Literature Review on the Effect of Cenegermin on Corneal Sensation and Innervation in Patients with Neurotrophic Keratopathy. (PubMed, J Ocul Pharmacol Ther) - "An 8-week course of cenegermin led to improvements in CS and CI in patients with NK, with greater relative gains observed among those patients with more severe disease. While study design heterogeneity and small sample sizes may limit the generalizability of these findings, the data support cenegermin's role in promoting corneal nerve regeneration."

Journal • Review • Dry Eye Disease • Keratitis • Ocular Inflammation • Ophthalmology

Observation of Corneal Nerve Regeneration after Oxervate Treatment with Confocal Microscopy - A Clinical Case. (PubMed, Klin Monbl Augenheilkd) - No abstract available

Journal

NGF-CP-201: Intranasal Cenegermin in Pediatric Participants with Spastic Cerebral Palsy. (clinicaltrialsregister.eu) - P1/2 | N=60 | Recruiting | Sponsor: Dompe' Farmaceutici S.p.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Cerebral Palsy • CNS Disorders • Pediatrics

Efficacy and Safety of Intranasal Cenegermin in Adult Participants With Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) (clinicaltrials.gov) - P3 | N=272 | Not yet recruiting | Sponsor: Dompé Farmaceutici S.p.A

New P3 trial • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain

NGF-CP-201: Intranasal Cenegermin in Pediatric Participants with Spastic Cerebral Palsy. (clinicaltrialsregister.eu) - P1/2 | N=60 | Not yet recruiting | Sponsor: Dompe' Farmaceutici S.p.A.

New P1/2 trial • Cerebral Palsy • CNS Disorders • Pediatrics

Mimicking Nature, Modulating Vision: Peptidomimetic Neurotrophin Agonists and Emerging Regenerative Strategies in Ocular Disease. (PubMed, Front Biosci (Landmark Ed)) - "This review highlights the development of neurotrophin receptor agonists-including recombinant nerve growth factor (NGF) (cenegermin), peptidomimetics (e.g., REC-0559, tavilermide), and synthetic microneurotrophins (BNN27, ENT-A010)-that target tropomyosin receptor kinases (TrkA/TrkB) and the p75 neurotrophin receptor (p75NTR) pathways to promote neuronal survival, synaptic plasticity, and tissue repair in neurotrophic keratitis, dry eye disease, and retinal degenerations. Parallel advances in peptide-based therapies address vascular and inflammatory pathologies: UPARANT and its derivatives modulate urokinase plasminogen activator receptor (uPAR)/formyl peptide receptor (FPR) signaling to inhibit angiogenesis and inflammation in diabetic retinopathy, whereas sphingosine 1 phosphate (S1P)-S1PR3 pepducins and integrin antagonists (risuteganib, THR-687, OTT166) offer multi-targeted strategies to stabilize the blood-retinal barrier and mitigate neovascularization...Further,..."

Journal • Review • CNS Disorders • Diabetic Retinopathy • Dry Eye Disease • Inflammation • Keratitis • Ocular Inflammation • Ophthalmology • Retinal Disorders • NGFR • NTRK2

Real-world landscape of drug-related ocular injuries: a retrospective pharmacovigilance study. (PubMed, Front Pharmacol) - "The top three drugs by signal strength were brolucizumab (ROR = 132.15), macrogol 400 (ROR = 117.96), and cenegermin (ROR = 60.19)...TTO analysis indicated that most drugs exhibited an "early failure type" (β < 1), such as dupilumab (β = 0.68); only two drugs exhibited a random failure type. The risk of drug-related ocular injuries is primarily associated with sensory organ drugs and biologics, with the greatest risk occurring during the early treatment phase. Clinical monitoring should prioritize female and elderly patients, especially regarding ocular symptoms at the onset of drug therapy, to strengthen pharmacovigilance and inform personalized medication."

Adverse events • Journal • Real-world evidence • Retrospective data • Cataract • Oncology • Ophthalmology

Current State of the Neurotrophin-Based Pharmaceutics in the Treatment of Neurodegenerative Diseases and Neuroinflammation. (PubMed, Med Sci (Basel)) - "The study identified limitations and future prospects for neurotrophin-based pharmaceuticals. For future clinical trials, attention should be paid to the pharmacogenetic profiles of the patients and the evaluation of the inflammatory status of the disease. Novel plasma biomarkers of the effectiveness are needed as well as TSPO-PET imaging. Drug delivery systems remain insufficient; therefore, efforts should focus on inducing endogenous neurotrophin production and developing highly selective agonists and antagonists of neurotrophin receptors. It is crucial to establish a favorable premorbid background before neurotrophin therapy to minimize immunoresistance."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies • Inflammation • Mental Retardation • Movement Disorders • Neuralgia • Ophthalmology • Pain • Parkinson's Disease • Psychiatry

Long-term outcomes of corneal neurotization for neurotrophic keratopathy: a dual center, single surgeon retrospective study. (PubMed, Plast Reconstr Surg) - "Corneal neurotization is highly effective and well-tolerated for managing NK, promoting a robust ocular surface that facilitates future rehabilitative surgeries."

Journal • Retrospective data • Dry Eye Disease • Ophthalmology

Targeted Therapies and Pharmacologic Advances in Mucous Membrane Pemphigoid: A Comprehensive Review. (PubMed, Dermatol Pract Concept) - "Considering the severity of the condition, progressive fibrosis, and resistance to therapy, more research is required in relation to the pathogenesis of MMP and the efficacy and safety profile of novel pharmacological options. Pharmacological agents should provide the achievement and maintenance of remission with minimal adverse effects. A broader spectrum of pharmacological agents will allow a personalized approach and more alternatives, in particular for recalcitrant cases, failure of the previous therapy, and in patients with MMP and malignancy."

Journal • Review • Dermatology • Fibrosis • Immunology • Infectious Disease • Oncology

Outcome of Cenegermin in the Treatment of Neurotrophic Keratopathy. (PubMed, Cornea) - "Cenegermin is an effective treatment of NK in the clinical setting, although a notable proportion of patients experience disease recurrence subsequently. Mackie staging is a significant prognostic factor for treatment success."

Journal • Dry Eye Disease • Ophthalmology

Dompé plans to apply the voucher to its Biologics License Application (BLA) for an intranasal form of Nerve Growth Factor (Cenegermin-bkbj) for the treatment of non-arteritic anterior ischemic optic neuropathy (NAION). (Businesswire) - "With this selection, Dompé receives a voucher shortening the marketing application review from the standard 10–12 months to just 1–2 months."

FDA event • Ophthalmology

Evaluation of in vitro and in vivo release of recombinant human nerve growth factor from bioengineered human stromal lenticule. (PubMed, Front Bioeng Biotechnol) - "Bioengineered lenticules exhibit sustained rhNGF release for at least 7 days in vitro and up to 1 month in vivo. These results, together with absence of adverse effects, and significant increase in CNFD at 4 weeks after lenticule implantation suggest its promising potential for clinical use."

Journal • Preclinical

Cenegermin for the Treatment of Moderate or Severe Neurotrophic Keratopathy: Results from a Prospective, Phase IV, Open-Label Study in China. (PubMed, Ophthalmol Ther) - "These findings demonstrate that cenegermin eye drops are an effective, generally well-tolerated treatment in Chinese patients with stage 2/3 NK, supporting their use in this patient population."

Clinical • Journal • P4 data • Dry Eye Disease • Keratitis • Ocular Inflammation • Ophthalmology • Pain

Corneal Neurotization vs. Cenergermin for Neurotrophic Keratitis: A Pilot Study (clinicaltrials.gov) - P=N/A | N=10 | Not yet recruiting | Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

New trial • Keratitis • Ocular Inflammation • Ophthalmology

Topical Cenegermin for Pediatric Neurotrophic Keratopathy: A Review of the Literature and Systematic Review. (PubMed, Cornea) - "Topical cenegermin seems to be an effective option for treating pNK. However, the current literature is limited, and prospective controlled studies are needed to study its effects further."

Journal • Dry Eye Disease • Keratitis • Ocular Inflammation • Ophthalmology • Pediatrics • Transplantation

Cenegermin treatment for pediatric neurotrophic keratopathy: a systematic review. (PubMed, Can J Ophthalmol) - "Cenegermin is a viable treatment option for pediatric NK, showing efficacy in improving corneal transparency and, to a lesser extent, visual acuity. However, its adoption is constrained by limited pediatric data, cost, and potential side effects. Further research is needed to establish long-term safety and effectiveness, and to optimize treatment protocols for this vulnerable population."

Journal • Corneal Abrasion • Dry Eye Disease • Infectious Disease • Ophthalmology • Pediatrics

Utility of cenegermin for the management of neurotrophic keratopathy after penetrating keratoplasty. (PubMed, Oman J Ophthalmol) - "Following an 8-week course of cenegermin, patients with a history of PK demonstrated improvement in NK stage, epithelial healing, and reduced epithelial defect size lasting 6 months after treatment completion. Patients with prior PK and NK may be considered candidates for cenegermin treatment."

Journal • Dry Eye Disease • Ophthalmology • Transplantation

The Role of Nerve Growth Factor on the Ocular Surface: A Review of the Current Experimental Research and Clinical Practices. (PubMed, Int J Mol Sci) - "Notably, recombinant human NGF (rhNGF, cenegermin) has been approved as the first topical biologic therapy for NK. Despite encouraging clinical outcomes, challenges such as high treatment costs, limited long-term data, and potential proangiogenic effects remain. This review consolidates current evidence on the role of NGF in ocular surface health and disease, highlighting its biological mechanisms, clinical applications, and future therapeutic potential."

Journal • Review • Cataract • Conjunctivitis • Dry Eye Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Transplantation

Selective Modulation of Trk Receptors by Cyclo-Organopeptides. (PubMed, ACS Chem Neurosci) - "Only humanized recombinant NGF has been clinically approved: Cenegermin for treatment of neurotrophic keratitis (NK) in the eye...This paper describes how those new cyclo-organopeptides were designed, prepared, and then selected via screens on Trk-transfected cells. It also outlines and explains obstacles which limit progress in this type of study."

Journal • Dry Eye Disease • Keratitis • Ocular Inflammation • Ophthalmology • BDNF

Real-World Safety Profile of Cenegermin Per FDA Adverse Event Reporting System. (PubMed, J Ocul Pharmacol Ther) - "Involvement of other organ systems is highly unlikely. Patients using topical cengermin should be counseled accordingly."

Adverse events • Journal • Real-world evidence • Keratitis • Ocular Inflammation • Ophthalmology • Pain

DOMPE -MT Neurotrophic Keratitis (clinicaltrials.gov) - P4 | N=10 | Active, not recruiting | Sponsor: Toyos Clinic

New P4 trial • Dry Eye Disease • Keratitis • Ocular Inflammation • Ophthalmology

Corneal Nerves After Treatment With Cenegermin (clinicaltrials.gov) - P=N/A | N=8 | Completed | Sponsor: University of California, Los Angeles | Active, not recruiting ➔ Completed | N=40 ➔ 8

Enrollment change • Trial completion • Keratitis • Ocular Inflammation • Ophthalmology

1953-2023. Seventy Years of the Nerve Growth Factor: A Potential Novel Treatment in Neurological Diseases? (PubMed, Aging Dis) - "In these instances, NGF holds promise for promoting tissue regeneration and repair. Challenges persist in addressing the complexity of neurodegenerative pathologies for a combined therapeutic approach."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Cardiovascular • CNS Disorders • Gene Therapies • Huntington's Disease • Movement Disorders • Musculoskeletal Diseases • Oncology • Orthopedics • Parkinson's Disease • Sarcoma • Solid Tumor • Vascular Neurology

Long-Term Therapeutic Effects of Topical Recombinant Human Nerve Growth Factor in Stage I Neurotrophic Keratitis and Retreatment Considerations (ARVO 2025) - "Purpose To evaluate the long-term therapeutic effects of topical recombinant human nerve growth factor (rhNGF; cenegermin) in patients with stage I neurotrophic keratitis (NK)...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Keratitis • Ocular Inflammation • Ophthalmology