recombinant lubricin (ECF843) / Dompe, Lubris BioPharma, Novartis - LARVOL DELTA

A structural and functional comparison between two recombinant human lubricin proteins: Recombinant human proteoglycan-4 (rhPRG4) vs ECF843. (PubMed, Exp Eye Res) - "Collectively, these data demonstrate ECF843 and rhPRG4 are significantly different in both structure and function. Given that a protein's structure sets the foundation for its interactions with other molecules and tissues in vivo, which ultimately determine its function, these differences most likely contributed to the disparate DED clinical trial results."

Journal • Dry Eye Disease • Inflammation • Ophthalmology • MMP9 • PRG4

Possible Strategies to Mitigate Placebo or Vehicle Response in Dry Eye Disease Trials: A Narrative Review. (PubMed, Ophthalmol Ther) - "This review briefly describes the factors that lead to placebo/vehicle response in DED trials and focuses on the aspects of clinical trial design that can be improved to mitigate vehicle response. In addition, it presents the observations from a recent ECF843 phase 2b study, wherein the study design approach consisted of a vehicle run-in phase, withdrawal phase, and masked treatment transition, and led to consistent data for DED signs and symptoms and reduced vehicle response post randomization."

Journal • Review • Dry Eye Disease • Ophthalmology

Biophysical and Functional Characterization of Recombinant Human Lubricin Proteins: rhPRG4 vs ECF843 (ARVO 2023) - "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."

Dry Eye Disease • Ophthalmology • MMP9 • PRG4

Effect of Recombinant Human Lubricin on Model Tear Film Stability. (PubMed, Transl Vis Sci Technol) - "In addition, the ability of rh-lubricin to maintain wetted area coverage is due to both freely dispersed and adsorbed rh-lubricin. Our platform and analysis method provide a facile, intuitive, and clinically relevant means to quantify the effect of ophthalmic drugs and formulations intended for improving tear film stability, as well as capture differences between variants related to drug stability and efficacy."

Journal • Immunology • Ophthalmology

PO070 - Efficacy and Safety of ECF843 (rhLubricin) in Patients With DED: A Randomized, Double-Masked, Phase 2b Study (AAO 2022) - "ECF843 showed no superiority vs vehicle in alleviating signs and symptoms of DED. Overall, it was safe and well tolerated."

Clinical • P2b data • Dry Eye Disease • Ophthalmology

Biophysical characterization of recombinant human Proteoglycan 4 (rhPRG4): Effect of Mg2+ and high pH (ARVO 2022) - "The clinically effective rhPRG4 assessed here had similar size and charge to native PRG4, and quickly adhered to Col1 (which is present on the ocular surface). The size, charge, and density for rhPRG4 are larger than those published for a different version of recombinant human lubricin (ECF843: Dh=~60nm, ~0mV, and a more compact 6.5S major peak), which recently did not produce supportive data in a dry eye clinical trial. Reduced Dh of rhPRG4 caused by Mg2+ and pH9-10 may be due to osmotic deswelling of the mucin domain and disulfide bond reshuffling, respectively, which are likely to affect function as well."

Dry Eye Disease • Ophthalmology • PRG4

Anti-inflammatory Function of Recombinant Human Lubricin (ECF843) on Human Corneal Epithelial Cells (AAO 2021) - "Fluorescent ECF843 was internalized by hTCEpi cells, more so with inflammatory stimuli, suggesting a mechanism of action that includes biological signaling pathways. Conclusion ECF843 has anti-inflammatory properties on human corneal epithelial cells and is under Phase 2 clinical evaluation."

Dry Eye Disease • Ophthalmology • CXCL5 • IL1B • IL6 • TNFA

Dry eye: What’s in the pipeline? (Review of Optometry) - "Francis Mah, MD...is intrigued by the drug’s mechanism of action. 'I think it’s really unique in that you’re potentially stimulating all three sources or layers of the tear film,' he says....There are several new cyclosporine products in various stages of development. According to John Sheppard, MD, who is in practice in Norfolk, Virginia, Novaliq is investigating two products based on the company's semifluorinated alkane water-free vehicle. 'They've come up with the first truly new vehicle [EyeSol] for topical eye medications in over a generation,' Dr. Sheppard says....Dr. Sheppard says that the beauty of looking at both osmolarity and MMP-9 is that the osmolarity acts as a normalizing comparator to further refine the accuracy of the MMP-9 test."

Media quote

A Study to Assess the Safety and Efficacy of ECF843 vs Vehicle in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2; N=719; Completed; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Completed; Trial completion date: Mar 2022 ➔ May 2021

Clinical • Trial completion • Trial completion date • Dry Eye Disease • Ophthalmology

A Study to Assess the Safety and Efficacy of ECF843 vs Vehicle in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2; N=680; Recruiting; Sponsor: Novartis Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dry Eye Disease • Ocular Infections • Ophthalmology

A Study to Assess the Safety and Efficacy of ECF843 vs Vehicle in Subjects With Dry Eye Disease (clinicaltrials.gov) - P2; N=680; Not yet recruiting; Sponsor: Novartis Pharmaceuticals

Clinical • New P2 trial • Conjunctivitis • Dry Eye Disease • Ophthalmology