RESTORE extension study demonstrates fully maintained initial vision gains with an average of 13.9 ranibizumab 0.5mg injections over three years for patients with visual impairment due to DMO (VI-DMO)[i]

New data for Lucentis® (ranibizumab) has demonstrated improvement in visual acuity achieved with individualised treatment after one year is maintained for up to three years on average in patients with VI-DMO, with fewer injections in years two and three compared to the first year and no additional or new safety risks identified1.

The findings come from the RESTORE extension study which showed that patients originally treated with ranibizumab on an individualised basis received an average of 13.9 injections over three years for VI-DMO patients1. In the extension study, 19-25% of patients, across all study arms, did not require any ranibizumab injections during years two and three. An average of 3.7 injections in the second year and 2.7 in the third year across the two ranibizumab arms were sufficient to fully maintain the mean of seven letters of visual acuity1.

Dr Sobha Sivaprasad, Consultant Ophthalmologist at King's College Hospital, London comments on the significance of the findings: "Laser treatment is the current standard of care for patients with visual impairment due to DMO but we know that it can only stabilise vision loss. Ranibizumab has been shown to lead to significant improvements in vision and quality of life in these patients.

The three year results from RESTORE are extremely important as they demonstrate that the visual acuity gains achieved with individualised treatment with ranibizumab can be maintained in the long-term, without any newly identified safety concerns for patients. Ranibizumab has become the standard of care in wet AMD and studies such as RESTORE help demonstrate the important role it also has to play in the treatment of visual impairment due to DMO. I hope that NICE will look at this new data and make a decision that gives national patient access to this innovative treatment."

The well characterised safety profile of ranibizumab in wet age-related macular degeneration (AMD) has been further supported by initial results from the pivotal LUMINOUSTM programme. LUMINOUS, one of the largest observational studies in ophthalmology, is designed to examine the long-term effectiveness and safety of ranibizumab in clinical practice across large populations and across all its licensed indications. This initial report represents retrospective one year data, made up of 4,500 wet AMD patients, and suggests there is no additional risk observed with real-life use of ranibizumab, as well as revealing confirmed low rates of adverse events over one year, compared to published outcomes from clinical trials of ranibizumab[ii].

Currently the UK has recruited over half of the 5,500 patients enrolled in the prospective arm of the study (as at August 2012) which is expected to recruit more than 30,000 patients from clinics across Asia, Australia, Europe, North and South America.

Dr. Mark Bechter, Medical Director at Novartis Pharmaceuticals UK Ltd, commenting on the significance of the LUMINOUS study said: "A wealth of data is already available on the safety and efficacy of ranibizumab from clinical trials, but the ongoing LUMINOUS study will provide real-life data on the long-term outcomes of ranibizumab in routine clinical practice across all its licensed indications. Novartis is committed to improving understanding and treatment of retinal vascular diseases and funds almost 40% of all industry sponsored ophthalmology trials. The information that this study generates will enable clinicians to provide better care for their patients on an individual basis and ultimately optimise outcomes."

Both the RESTORE extension study and LUMINOUS retrospective one year data will be presented at the 12th European Society of Retina Specialists (EURETINA) Congress in Milan, Italy, 6-9 September 2012.

About RESTORE

Core Study

In the RESTORE core study, 345 patients with VI-DMO were treated with ranibizumab (monotherapy or combined with laser) or laser alone on a monthly basis for a duration of 12 months with a 24 month extension. Results showed that ranibizumab monotherapy or in combination with laser resulted in significantly greater improvement in visual acuity compared with laser alone. Eyes treated with ranibizumab gained 6.8 letters above baseline compared with 0.9 letters with laser only and results were sustained over 12 months of therapy. Significantly more (2-3 fold) ranibizumab‐treated patients gained ≥10 or ≥15 letters compared with laser monotherapy. In terms of safety there was a low incidence of arterial thromboembolic events (ATEs) (2.7-3.5%) in all groups.

Extension Study

In the RESTORE extension study, 240 patients from the core study were taken forward to receive individualised treatment with ranibizumab according to a regimen consistent with the European Union label. Results showed that patients who were originally treated with ranibizumab received an average of 13.9 injections over three years. 19-25% of patients across all study arms did not require any ranibizumab injections during years two and three. An average of 3.7 injections in the second year and 2.7 in the third year across the two ranibizumab arms were sufficient to fully maintain the mean of seven letters of visual acuity gained. The safety profile was consistent with previous studies conducted in other indications.

About LUMINOUS

The LUMINOUS programme is one of the largest observational studies in ophthalmology and consists of two parts launched in 2011. The retrospective element of the LUMINOUS programme pooled data from four European registries of nearly 4,500 wet AMD patients and showed no new safety signals for ranibizumab at one year, compared to published outcomes from clinical trials of ranibizumab, further reinforcing its well-characterised safety profile. The retrospective data also revealed confirmed lower rates of key adverse events at 12-months and a low number of ranibizumab injections were observed during the first year. The mean number of injections over twelve months ranged from 4.3 to 5.0 (based on all patients) and 4.7 to 5.5 (based on patients completing one year).

The prospective element of the LUMINOUS programme is expected to provide important long-term evidence on the real-world effectiveness and safety profile of ranibizumab in its licensed indications. This 5-year study is ongoing and currently has more than 5,500 patients enrolled. It is expected to recruit more than 30,000 patients from clinics across Asia, Australia, Europe, North and South America.

The LUMINOUS Steering Committee (LSC), an external advisory board made up of medical experts, representatives from patient organisations and other experts, will provide guidance and interpretation of the data as it is collected. As an observational study, LUMINOUS will not direct therapy or recommend any specific therapy.

About Lucentis® (ranibizumab)

Ranibizumab is an anti-vascular endothelial growth factor (anti-VEGF) licensed for the treatment of visual impairment due to macular oedema secondary to Retinal Vein Occlusion (RVO) (central and branch), visual impairment due to Diabetic Macular Oedema (DMO) and wet Age Related Macular Degeneration (AMD). Lucentis is approved by the National Institute for Health and Clinical Excellence (NICE) for the treatment of wet AMD and by the Scottish Medicines Consortium (SMC) for wet AMD and the treatment of vision loss due to macular oedema secondary to Central-Retinal Vein Occlusion (CRVO). Ranibizumab was developed by Genentech and Novartis. Genentech has the commercial rights in the US, while Novartis has exclusive rights in the rest of the world.

Excellence in Ophthalmology

Excellence in Ophthalmology is a medical education programme designed to help improve patient care by providing training and professional development for the ophthalmic community in the UK. Organised and funded by Novartis and Alcon, as part of the Novartis commitment to ophthalmology, Excellence in Ophthalmology is guided by a steering committee of leading medical retina professionals.

Novartis and Alcon sponsor the eXcellence in Ophthalmology Vision Award (XOVA). XOVA is an annual award launched in 2010 that provides funding to non-profit initiatives and projects that will have a positive impact on improving the quality of eye care and make a significant impact in addressing unmet needs in the fields of ophthalmology and optometry.