tivanisiran (SYL1001) / PharmaMar - LARVOL DELTA

Quintessence of currently approved and upcoming treatments for dry eye disease. (PubMed, Graefes Arch Clin Exp Ophthalmol) - "Currently, the US Food and Drug Administration (FDA)-approved medical treatments for treatment of DED include cyclosporine formulations (RESTASIS® [cyclosporine 0.05% ophthalmic emulsion], VEVYE® [cyclosporine 0.1% ophthalmic solution], and CEQUA™ [cyclosporine 0.09% ophthalmic solution]), XIIDRA® (lifitegrast), a leukocyte function-associated antigen-1 (LFA-1)/intracellular adhesion molecule-1(ICAM-1) inhibitor, EYSUVIS™ (loteprednol etabonate ophthalmic suspension 0.25%), a corticosteroid, and MIEBO™ (perfluorohexyloctane ophthalmic solution), a semifluorinated alkane. TYRVAYA™ (varenicline solution nasal spray), a cholinergic agonist, is another formulation approved for the treatment of the signs and symptoms of DED...Cyclosporine formulations TJO-087 (cyclosporine A nanoemulsion 0.08%), SCAI-001 eye drops (cyclosporine 0.01%, 0.02%) are being evaluated against RESTASIS® and other approved treatments. The potential treatments being assessed include..."

Journal • Review • Conjunctivitis • Dry Eye Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Sjogren's Syndrome • ICAM1

Tivanisiran for Dry Eye in Subjects With Sjögren's Syndrome (clinicaltrials.gov) - P3 | N=203 | Completed | Sponsor: Sylentis, S.A. | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Immunology • Ophthalmology • Sjogren's Syndrome

FYDES: Safety Study of Tivanisiran to Treat Dry Eye (clinicaltrials.gov) - P3 | N=301 | Completed | Sponsor: Sylentis, S.A. | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

Long-term safety studies of tivanisiran for the treatment of Dry Eye Disease (DED) (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."

Clinical • Dry Eye Disease • Ocular Inflammation • Ophthalmology

Tivanisiran for Dry Eye in Subjects With Sjögren's Syndrome (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Sylentis, S.A. | Trial completion date: Feb 2023 ➔ Feb 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology • Sjogren's Syndrome

FYDES: Safety Study of Tivanisiran to Treat Dry Eye (clinicaltrials.gov) - P3 | N=301 | Active, not recruiting | Sponsor: Sylentis, S.A. | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

Tivanisiran for Dry Eye in Subjects With Sjögren's Syndrome (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Sylentis, S.A. | Trial completion date: Jun 2022 ➔ Feb 2023 | Trial primary completion date: Apr 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology • Sjogren's Syndrome

Sylentis announces results of phase 3 HELIX trial with tivanisiran for the treatment of dry eye disease (Pharmamar Press Release) - P3, N=300; HELIX (NCT03108664); Sponsor: Sylentis, S.A; "Sylentis...has announced today the results of the HELIX exploratory clinical trial...A clinically relevant improvement in the primary endpoint of total corneal staining has also been demonstrated. Nevertheless, the primary endpoints of ocular pain and total corneal staining have not been met...The complete results and additional analysis from the HELIX clinical trial will be presented at the Annual Congress of the Association for Research in Vision and Ophthalmology (ARVO), to be held in Vancouver in April 2019. In addition, these data will be presented to the FDA and other regulatory authorities during the second quarter of 2019 to define the future strategy."

P3 data • Dry Eye Disease • Ophthalmology

FYDES: Safety Study of Tivanisiran to Treat Dry Eye (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Sylentis, S.A.

New P3 trial • Dry Eye Disease • Ophthalmology

Tivanisiran for Dry Eye in Subjects With Sjögren's Syndrome (clinicaltrials.gov) - P3; N=200; Recruiting; Sponsor: Sylentis, S.A.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Dry Eye Disease • Ophthalmology • Sjogren's Syndrome

Experimental Pharmacotherapy for Dry Eye Disease: A Review. (PubMed, J Exp Pharmacol) - "Moreover, the most advanced experimental strategies in the pipeline for DED, tivanisiran, IL-1R antagonist EBI-005 and SkQ1, are being tested in Phase III clinical trials, still ongoing. Nevertheless, although promising results, further studies are still needed to confirm efficacy and safety of the new emerging therapies for DED."

Journal • Review • Dry Eye Disease • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Pain

Tivanisiran for Dry Eye in Subjects With Sjögren's Syndrome (clinicaltrials.gov) - P3; N=200; Not yet recruiting; Sponsor: Sylentis, S.A.

Clinical • New P3 trial • Dry Eye Disease • Ocular Infections • Ophthalmology

The growth of siRNA-based therapeutics: updated clinical studies. (PubMed, Biochem Pharmacol) - "This review provides a brief overview of mechanisms of siRNA action, physiological barriers to its delivery and activity, and the most common chemical modifications and delivery platforms used to overcome these barriers. Furthermore, this review presents comprehensive profiles of the three approved siRNA drugs (patisiran, givosiran, and lumasiran) and the seven other siRNA candidates in Phase 3 clinical trials (vutrisiran, nedosiran, inclisiran, fitusiran, teprasiran, cosdosiran, and tivanisiran), summarizing their modifications and delivery strategies, disease-specific mechanisms of action, updated clinical trial status, and future outlooks."

Clinical • Journal • Review • Dyslipidemia • Metabolic Disorders

RNA therapeutics in ophthalmology - translation to clinical trials. (PubMed, Exp Eye Res) - "This review provides a detailed insight into the recent developments and clinical trials that have been conducted for several gene-silencing therapies, including ISTH0036, SYL040012, SYL1001, PF-04523655, Sirna-027, QR-110, QR-1123, QR-421a and IONIS-FB-L in glaucoma, dry eye disease, age-related macular degeneration, diabetic macular oedema and various inherited retinal diseases. Our aim is to explore the potential of these drugs whilst evaluating their associated advantages and disadvantages, and to discuss the future translation of RNA therapeutics in ophthalmology."

Clinical • Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Diabetic Macular Edema • Dry Age-related Macular Degeneration • Dry Eye Disease • Glaucoma • Macular Degeneration • Macular Edema • Ocular Infections • Ophthalmology • Retinal Disorders

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market. (PubMed) - Pharm Res - "...The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3)...Miravirsen is an AntimiR-122 for hepatitis C virus infection. The flexibility of RNAi technology is easily understood taking into account: (i) the different drug targets (i.e. p53, caspase 2, PKN3, β2-adrenergic receptor, mutated KRAS, microRNAs); (ii) therapeutic conditions, including ophthalmic diseases, kidney injury, amyloidosis, pancreatic cancer, viral hepatitis; and (iii) routes of administration (ocular, intravenous, subcutaneous, intratumoral). Although some issues are still matters of concern (delivery, toxicity, cost, and biological barriers), RNAi definitively opens a wide avenue for drug development."

Journal • Review • Biosimilar • Gastrointestinal Cancer • Hepatitis C Virus • Immunology • Oncology • Ophthalmology • Pancreatic Cancer • Renal Disease

HELIX, a Double-masked Study of SYL1001 in Patients With Moderate to Severe Dry Eye Disease (DED) (clinicaltrials.gov) - P3; N=300; Not yet recruiting; Sponsor: Sylentis, S.A.

New P3 trial • Biosimilar • Dry Eye Disease • Ophthalmology

HELIX, a Double-masked Study of SYL1001 in Patients With Moderate to Severe Dry Eye Disease (DED) (clinicaltrials.gov) - P3; N=300; Recruiting; Sponsor: Sylentis, S.A.; Trial primary completion date: Jul 2018 ➔ Dec 2018

Trial primary completion date • Biosimilar • Conjunctivitis • Dry Eye Disease • Ocular Inflammation • Ophthalmology

Safety and Efficacy Clinical Trials for SYL1001, a Novel Short Interfering RNA for the Treatment of Dry Eye Disease. (PubMed) - Invest Ophthalmol Vis Sci - P1,P1/2,P2; "SYL1001 showed a large safety margin and may provide novel therapeutic opportunity for the relief of dry eye. (ClinicalTrials.gov numbers, NCT01438281, NCT01776658, and NCT02455999.)."

Journal • Biosimilar • Dry Eye Disease • Ophthalmology

Tivanisiran as a new treatment for Dry Eye in patients with Sjögren Syndrome (ARVO 2020) - P3; "Sylentis is developing a new product targeting dry eye signs and symptoms, which has shown higher clinical performance in patients suffering from Sjögren Syndrome.Methods Tivanisiran (former SYL1001) is a 19-nucleotide small interference RNA designed to silence the transient receptor potential cation channel subfamily V member 1 (TRPV1) mRNA...An exploratory analysis was conducted in patients with Sjögren Syndrome (n=30) for primary and secondary endpoints. Visual analogue scale (VAS) for pain, total Corneal Fluorescein staining (CFS) and hyperemia were the primary endpoints in this clinical trial, whereas DED symptom index, TBUT, areas of CFS, Schirmer test and quality of life questionnaires were included as secondary outcomes.Results Results in this phase 3 clinical trial showed an improvement in all VAS parameters (pain, dryness, burning/stinging, itching, foreign body sensation), total CFS (p=0.030) and CFS by areas, as well as in quality of life..."

Clinical

EPIDEMIOLOGY OF DRY EYE DISEASE IN TAIWAN (COPHy AA 2020) - "The management of DED, relies not only on traditional medications such as artificial tears, gels and ointments, but also newer treatment options such as acupuncture, SYL1001, and nanomedicine therapy. We also conducted a comprehensive literature review including common subtypes and treatment of DED. Clearly, more clinical trials are needed to assess the efficacy and safety of the various treatments and common subtypes of DED."

Clinical

Dry Eye Disease: A Review of Epidemiology in Taiwan, and its Clinical Treatment and Merits. (PubMed, J Clin Med) - "...The management of DED, relies not only on traditional medications such as artificial tears, gels and ointments, but also newer treatment options such as acupuncture, SYL1001, and nanomedicine therapy. We also conducted a comprehensive literature review including common subtypes and treatment of DED. Clearly, more clinical trials are needed to assess the efficacy and safety of the various treatments and common subtypes of DED."

Clinical • Journal • Review

Sylentis (PharmaMar Group) presents new results of tivanisiran for the treatment of dry eye disease (Pharmamar Press Release) - P3, N=330; HELIX (NCT03108664); Sponsor: Sylentis, S.A; "Sylentis, a pharmaceutical company of the PharmaMar...has presented new results from its clinical trial HELIX with tivanisiran for the treatment of dry eye disease during the Annual Congress of the Association for Research in Vision and Ophthalmology (ARVO), which is being held from 28th April to 2nd May in Vancouver...In the new data obtained from HELIX clinical trial, it has been identified that in patients....a statistically significant improvement was observed both in signs and symptoms."

P3 data

Clinical Results of tivanisiran, a siRNA for the treatment of dry eye disease (ARVO 2019) - P1/2, P3; "Purpose To present the results obtained in phase 2 (SYL1001_II, NCT01776658, EudraCT No: 2012-001177-93) and phase 3 (HELIX, NCT03108664, EudraCT No: 2016-003903-79) clinical trials...No unexpected or serious related AEs have occurred, suggesting excellent local and systemic tolerability Conclusions Phase II trials for tivanisiran 1.125% showed a significant improvement in VAS for ocular discomfort/pain and conjunctival hyperemia; the phase III trial confirmed the safety profile and will further document the effect of tivanisiran on this disease. Up to date, few therapeutic options are available and tivanisiran represents a new class of drugs for patients suffering from DED."

Clinical

HELIX, a Double-masked Study of SYL1001 in Patients With Moderate to Severe Dry Eye Disease (DED) (clinicaltrials.gov) - P3; N=330; Completed; Sponsor: Sylentis, S.A.; Recruiting ➔ Completed

Trial completion