Randomized Clinical Trial Evaluating Intravitreal Ranibizumab or Saline for Vitreous Hemorrhage From Proliferative Diabetic Retinopathy.


Importance  Vascular endothelial growth factor plays a role in proliferative diabetic retinopathy (PDR). Intravitreal injection of saline has been shown potentially to lead to improved visual acuity compared with observation alone in eyes with vitreous hemorrhage. Therefore, it is important to determine if intravitreal anti–vascular endothelial growth factor can reduce vitrectomy rates (and risks associated with vitrectomy) compared with saline for vitreous hemorrhage from PDR that precludes placement or confirmation of complete panretinal photocoagulation.

Objective  To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage from PDR.

Design  Phase 3, double-masked, randomized, multicenter clinical trial. Data reported were collected from June 2010 to March 2012 and include 16 weeks of follow-up.

Setting  Community-based and academic-based ophthalmology practices specializing in retinal diseases.

Participants  Two hundred sixty-one eyes of 261 study participants, who were at least 18 years of age with type 1 or type 2 diabetes mellitus. Study eyes had vitreous hemorrhage from PDR precluding panretinal photocoagulation completion.

Intervention  Eyes were randomly assigned to 0.5-mg intravitreal ranibizumab (n = 125) or intravitreal saline (n = 136) at baseline and 4 and 8 weeks.

Main Outcome Measure  Cumulative probability of vitrectomy within 16 weeks.

Results  Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab vs 17% with saline (difference, 4%; 95% CI, −4% to 13%) and of complete panretinal photocoagulation without vitrectomy by 16 weeks was 44% and 31%, respectively (P = .05). The mean (SD) visual acuity improvement from baseline to 12 weeks was 22 (23) letters and 16 (31) letters, respectively (P = .04). Recurrent vitreous hemorrhage occurred within 16 weeks in 6% and 17%, respectively (P = .01). One eye developed endophthalmitis after saline injection.

Conclusions and Relevance  Overall, the 16-week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with vitreous hemorrhage from PDR. Short-term secondary outcomes including visual acuity improvement, increased panretinal photocoagulation completion rates, and reduced recurrent vitreous hemorrhage rates suggest biologic activity of ranibizumab. Long-term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab injection are different than observation alone cannot be determined from this study.

 

Source: JAMA

 

 

Real-world data at ARVO highlight transformational outcomes seen with Lucentis®, including lower injection frequency than in original clinical trials.


nova

 

 

  • UK real world study shows 59% reduction of legal blindness attributable to wet AMD since introduction of Lucentis with 9.7 injections spread over 5 years
     
  • New one year REPAIR data shows visual acuity improvement of 14 letters with an average of 3.6 Lucentis injections in myopic CNV patients
     
  • Largest Lucentis meta-analysis, over 10,000 patients, confirms well-established safety profile reported from extensive clinical trials and real-world experience

Novartis has reported that new data with the eye drug Lucentis® (ranibizumab), first licensed in June 2006, is highlighted in a total of 209 abstracts at the 2013 Association for Research in Vision and Ophthalmology (ARVO) annual meeting this week. This research across multiple retinal disease areas, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularization (CNV), demonstrates that Lucentis with a wealth of real world long term experience is the pioneering anti-VEGF ocular treatment with its transformational efficacy, individualized treatment regimen, and well established long-term safety profile.

“Lucentis was designed to save sight and this is further demonstrated by the wealth of data in multiple disease areas reported at ARVO this week. In patients with myopic CNV average VA gains were 14 letters with an average of 3.6 injections,” said Dr Timothy Wright, Global Head Development, Novartis Pharma AG. “Real world evidence shows a lower number of injections and clinic visits than in the original studies with Lucentis, whilst achieving an over 50 percent reduction of blindness due to wet AMD.”

Lucentis ARVO highlights include:
Real world evidence in wet AMD: One study looked at how Lucentis treatment impacted the rates of legal blindness secondary to wet AMD in Scotland, UK. Blind registration data from the Royal National Institute for the Blind was retrospectively analyzed. It was reported that since the commencement of treatment with Lucentis there was a 59% reduction in the incidence rate of legal blindness attributable to wet AMD. The mean number of clinic visits decreased by year, with 9.0 in year one, 5.8 in year two, 4.8 in year three, 2.3 in year four and 0.5 in year five; the average number of injections was 9.7 spread over 5 years. This study highlights how the transformational efficacy of Lucentis translates into clinical real-world practice[1]. [Oral session 118]

DME: The response rates were evaluated in patients with DME in the RESTORE trial. Patients were treated with Lucentis 0.5 mg (monotherapy or combined with laser) or laser alone for a duration of 12 months, at 12 months all patients were eligible for Lucentis 0.5mg as-needed and the study was extended to 36 months. The patients who responded better to Lucentis treatment were the ones who were more recently diagnosed with DME, highlighting the need for prompt therapy[2]. [Poster session 290]

Myopic CNV: In the prospective, multicenter trial of Lucentis in myopic CNV patients, the REPAIR study, the primary endpoint was the mean gain in letters from baseline visual acuity at 12 months. At month 12 the mean visual acuity gain was 13.8 letters, this was achieved with a low number of injections to month 12 (mean 3.6, median 3) with 21% patients requiring only the one baseline treatment[3]. [Poster session 314]

Safety profile of Lucentis: In the largest comprehensive evaluation of Lucentis safety data to date, a meta-analysis examining the systemic safety profile of Lucentis across 22 studies and 10,300 patients, the safety profile of was reported to be consistent with that from individual randomized, controlled clinical trials[4]. [Poster session 234]

LUMINOUS, a 5-year, global, prospective, observational, long-term study to evaluate the safety and effectiveness of Lucentis 0.5 mg across its licensed indications is being conducted. This global study, approximately 500 centers in 34 countries worldwide, aims to enroll 30,000 patients. The baseline characteristics of the first cohort of patients enrolled were as expected and are representative of patients from a real-world setting[5]. [Poster session 375]

About Lucentis® (ranibizumab)
Lucentis is a humanized therapeutic antibody fragment designed to block all biologically active forms of vascular endothelial cell growth factor-A (VEGF-A). Increased levels of VEGF-A are seen in wet AMD and other ocular diseases such as diabetic macular edema (DME) and retinal vein occlusion (RVO). Lucentis was specifically designed for the eye, minimizing systemic exposure.

Lucentis is licensed for the treatment of wet AMD in more than 100 countries, in more than 90 countries for the treatment of visual impairment due to DME and in 90 countries for visual impairment due to macular edema secondary to RVO, including both branch- and central-RVO. Novartis submitted regulatory approval for Lucentis for the treatment of myopic CNV in the European Union in the third quarter of 2012. In many countries, including those in Europe, Lucentis has an individualized treatment regimen with the goal of maximizing visual outcomes while minimizing under- or over-treating patients.

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.

Lucentis has a well-established safety profile supported by 43 extensive sponsored clinical studies and real-world experience. Its safety profile has been well established in a clinical development program that enrolled more than 12,500 patients across indications and there is more than 1.7 million patient-treatment years of exposure since its launch in the United States in 2006.

Lucentis was developed by Genentech and Novartis. Genentech has the commercial rights to Lucentis in the United States. Novartis has exclusive rights in the rest of the world. Lucentis is a registered trademark of Genentech Inc.

Source: Novartis newsletter

 

 

New data for Novartis drug Lucentis® confirms long-term efficacy and safety profile and benefits of individualized treatment .


  • REPAIR study shows an average of three Lucentis® injections improve visual acuity in patients with myopic choroidal neovascularization
  • RESTORE extension study demonstrates DME patients fully maintained initial vision gains with an average of 13.9 Lucentis injections over three years
  • Retrospective analysis reinforces Lucentis well-characterized safety profile in wet AMD; ongoing LUMINOUSTM program now involves over 10,000 patients

 

New data for Lucentis® (ranibizumab), the only anti-VEGF therapy licensed across three ocular indications, show that individualized treatment with Lucentis provides sustained improvement in vision with a low number of injections. It is estimated that over 80% of visual impairment is preventable when due to conditions such as wet age-related macular degeneration (wet AMD), diabetic macular edema (DME), and visual impairment due to macular edema secondary to retinal vein occlusion (RVO)[1]. These conditions can eventually lead to blindness if left untreated.

 

“Lucentis has become the standard of care in wet AMD and has helped to significantly improve vision in a majority of patients with this disease.” said Tim Wright, Global Head of Development, Novartis Pharma. “These new data confirm that an individualized treatment approach can lead to optimal improvements in vision with a low average number of treatments, thus ensuring that patients with retinal diseases are not over- or under-treated. In addition, these data add to the well-characterized safety profile of Lucentis”.

 

Lucentis also demonstrated benefits in visual acuity outcomes in patients with visual impairment due to choroidal neovascularization (CNV) secondary to pathological myopia (PM). Lucentis is currently not approved to treat this condition. Novartis will submit for regulatory approval in this indication in the European Union in the third quarter of this year and in Japan by the end of 2012.

 

Novartis is dedicated to the research, development and manufacturing of ophthalmic pharmaceuticals. The mission of Novartis in the field of ophthalmology is to discover, develop and manufacture innovative products to improve eye health and enhance people’s lives.

 

Lucentis study highlights at the 12th European Society of Retina Specialists (EURETINA) Congress in Milan, Italy include[2]-[4]:

 

REPAIR

This one year study performed in twelve centers in the United Kingdom explored the efficacy and safety profile of 0.5 mg Lucentis administered on an individualized basis in 65 patients with myopic CNV. After six months of treatment, mean visual acuity improved by twelve letters. Patients received an average of three Lucentis injections with 29 % requiring no further treatment beyond the first injection. This analysis shows that Lucentis therapy leads to improvement in visual acuity in patients with this condition. The six month interim results and the full one year data will be presented at Euretina. Currently, photodynamic therapy with Visudyne® (verteporfin) is the only approved medical treatment for this condition.

 

RESTORE

In the RESTORE extension study, 240 patients with DME received individualized treatment with Lucentis according to a regimen consistent with the European Union label. Results showed that patients who were originally treated with Lucentis received an average of 13.9 injections over three years. 19-25% of patients across all study arms did not require any Lucentis injections during years two and three. An average of 3.7 injections in the second year and 2.7 in the third year were sufficient to fully maintain the mean of seven letters of visual acuity gained in the RESTORE core study. The safety profile was consistent with previous studies conducted in other indications. There were no cases of endophthalmitis reported within the RESTORE core and extension studies.

 

“The results of this study show that individualized treatment with Lucentis can lead to a significant improvement in vision and that these improvements are sustained in the long term” said Professor Francesco Bandello, Department of Ophthalmology, Hospital San Raffaele, University Vita Salute San Raffaele, Milan, Italy and president elect of EURETINA. “It is important that we explore how these insights apply to real-world clinical practice to ensure that we are providing the best possible care for our patients”.

 

LUMINOUS

The Luminous program is one of the largest observational studies in ophthalmology and consists of two parts launched in 2011. The retrospective part comprises pooled data from four European registries of nearly 4,500 patients with wet AMD treated with Lucentis. These data showed no new safety signals for Lucentis and reinforces its well-characterized safety profile. The registries revealed low incidences of key adverse events at 12-months. Additionally, a low number of Lucentis injections were observed during the first year. The mean number of Lucentis 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 part of Luminous is expected to provide important long-term evidence on the real-world effectiveness and safety profile of Lucentis 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.

 

About Lucentis® (ranibizumab)

Lucentis is a humanized therapeutic antibody fragment designed to block all biologically active forms of vascular endothelial cell growth factor-A (VEGF-A). Increased levels of VEGF-A are seen in wet AMD and other ocular diseases such as diabetic macular edema (DME) and retinal vein occlusion (RVO). Lucentis has been designed, developed and formulated specifically for use in ocular disease with the aim of stabilizing and improving visual acuity in these patients, while minimizing the risk of systemic side effects.

 

Lucentis is licensed for the treatment of wet AMD in more than 100 countries, in more than 80 countries for the treatment of visual impairment due to DME and in 80 countries for visual impairment due to macular edema secondary to RVO, including both branch- and central-RVO. In many countries, including those in Europe, Lucentis has an individualized treatment regimen with the goal of maximizing visual outcomes while minimizing under- or over-treating patients.

 

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.

 

Lucentis has a well-characterized safety profile and Novartis systematically monitors the safety and tolerability of Lucentis for licensed indications on an ongoing basis. Its safety profile has been well established in a clinical development program that enrolled more than 10,000 patients across indications. Since its launch in the United States in 2006, there are more than one million patient-treatment years of exposure for Lucentis.

 

Serious adverse events related to the injection procedure include endophthalmitis, retinal detachment, retinal tear and traumatic cataract. Other serious ocular events observed among Lucentis-treated patients included intraocular inflammation and increased intraocular pressure. Non-eye related serious side effects, although not common, include heart attacks, strokes and death.

 

Lucentis was developed by Genentech and Novartis. Genentech has the commercial rights to Lucentis in the United States. Novartis has exclusive rights in the rest of the world. Lucentis is a registered trademark of Genentech Inc.

 

References

[1] Pascolini D and Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol 2012;96:614-618.

[2] Tufail A on behalf of the REPAIR study group. The REPAIR study: 12 Month, prospective, multi-center trial of ranibizumab in choroidal neovascularization (CNV) due to pathological myopia (PM). EURETINA 2012.

[3] Lanzetta P on behalf of the RESTORE study group. Long-term safety and efficacy outcome of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema: the RESTORE extension study. EURETINA 2012.

[4] Bandello F on behalf of the LUMINOUS group. Outcomes of the retrospective pooled safety analysis of ranibizumab therapy for neovascular age-related macular degeneration from four european registries and update on the ongoing prospective analysis for the LUMINOUS study. EURETINA 2012.

 

 

Source: Novartis newsletter