Date: 2014-05-12
Type of information:
phase: 3
Announcement: publication of results in Ophthalmology, the Journal of the American Academy of Ophthalmology
Company: Gene Signal (Switzerland)
Product: aganirsen
Action
mechanism: Aganirsen is an antisense oliglonucleotide that inhibits the expression of insulin receptor substrate-1 (IRS-1). It has also antiangiogenic activities including inhibition of both VEGF and interleukin-1β expression.
Disease: corneal neovascularisation due to inflammation (keratitis)
Therapeutic area: Ophtalmological diseases
Country:
Trial
details: I-CAN is the first randomised trial of a topical inhibitor of corneal angiogenesis. It was a European multicentre, double-masked, randomised placebo-controlled Phase III study. Sixty nine (69) patients with keratitis-related progressive corneal neovascularisation (CNV) were randomised to receive aganirsen (34) or placebo (35). Patients applied aganirsen eye drops (GS-101) with one drop twice a day of a 86 mg/ml solution or placebo, for 90 days treatment with a follow up at 180 days. Aganirsen was administered on top of current standard of care (e.g. corticoids, antiviral and immunosuppressant therapies).
Latest
news: * On May 12th 2014, Gene Signal, a biotechnology company focused on developing innovative drugs to manage angiogenesis-based medical conditions, and the Department of Ophthalmology, University of Cologne Medical Centre, Germany, have announced that positive data from the I-CAN study of aganirsen eye drops (GS-101) was published in Ophthalmology, the Journal of the American Academy of Ophthalmology. The next step for the company is to discuss the results of the I-CAN study with the regulatory authorities to design a short confirmatory and pivotal study.
The regulatory authorities recommended the I-CAN study to be the first randomised clinical trial in the front of eye disease CV to use visual acuity as a primary endpoint. The results based on the whole patient population included in the study showed no statistical difference in VA scores between aganirsen and placebo patient groups. However the I-CAN study demonstrated a number of other efficacy results with positive data for topical aganirsen:
- Significantly reduced by 26.2% (p=0.014) the relative area of corneal neovascularisation after 90 days and this improvement persisted after 180 days (reduction of 26.6%, p=0.012)
- Tended to lower the need for cornea transplantation at day 180 (p=0.087) in the intent to treat (ITT) population
- However, in those patients with viral keratitis (inflammation) and central neovascularisation, it significantly reduced the need for cornea transplantation at both day 90 (p=0.014) and at day 180 (p=0.012)
- In those patients with traumatic/viral keratitis (inflammation), it tended to lower the risk of graft rejection at day 90 (p=0.162)
- In terms of Quality of Life, there were significant improvements in composite and near activity sub scores (p=0.039 and 0.026 respectively) at day 90 in the per protocol aganirsen population.
The I-CAN study reiterated the excellent safety and tolerability profile of aganirsen, which has now been used in over 220 patients in clinical trials and for compassionate use:
- Similar numbers of treatment-emergent adverse events (TEAEs) were observed in both aganirsen and placebo patient groups
- Ocular TEAEs were lower in aganirsen patients (11.1%) compared to placebo patients (18.4%)
- Most TEAEs were of mild or moderate severity and there was no evidence of increased incidence of severe TEAEs in either patient group
- Patient compliance was 95% for aganirsen patients, a remarkable result for such a painful ophthalmologic condition.
