Very limited published evidence of safety

Negligible levels anticipated in milk due to the drug’s properties

Sep 19 · Licence change approved in EU [9].

Jul 19 · Recommended for EU approval by CHMP - the additional indication is "treatment of retinopathy of prematurity (ROP) with zone I (stage 1+, 2+, 3 or 3+), zone II (stage 3+) or AP-ROP (aggressive posterior ROP) disease." [7].

Dec 18 · Pre-registration in EU [6].

Mar 17 · Filings planned for 2018 [2].

ROP develops in 16% of all premature births, the figure rising to around 60% of infants weighing less than 1500 g at birth and 65% for infants less than 1250 g; however, severe ROP is uncommon. A review in the USA in 2008 looked at 4.67 million live births. The total incidence of ROP was 0.12% overall and 7.35% for premature infants with hospital stay greater than 14 days [1].

Sep 19 · PIII RAINBOW (n=225) study is published; it reports higher rate of treatment success (survival with no active retinopathy) with ranibizumab 0.2 mg vs. laser therapy, but this was of borderline statistical significance (80% vs. 66%; OR 2.19, 95% Cl 0.99–4.82, p=0.051) [8].

Sep 18 · Novartis announced that treatment with ranibizumab did not meet the primary endpoint in the global randomised, parallel-assignment, open-label, PIII RAINBOW trial (n=300), and marginally missed statistical significance for demonstrating superiority to laser surgery. However, since 80% of patients achieved treatment success with ranibizumab vs 66% with laser, the company still plans to file outside of the US for this indication [5].

Dec 17 · PIII RAINBOW trial (NCT02375971) completed [4].

Jun 16 · Novartis initiates the extension study RAINBOWExt in patients who were treated for ROP in the core RAINBOW study (CRFB002H2301E1; NCT02640664). The study intends to enrol approximately 300 patients in Belgium, Estonia, Hungary, Slovakia, Italy, Lithuania, Czech Republic and Austria [3].

Dec 15 · Novartis initiates the PIII RAINBOW trial to evaluate efficacy and safety of intravitreal ranibizumab compared with laser therapy for the treatment of infants born prematurely with retinopathy of prematurity (CRFB002H2301; NCT02375971). The randomised, parallel-assignment, open-label, controlled trial intends to enrol 300 patients in Austria, Belgium, Croatia, Czech Republic, Estonia, France, Slovakia, Denmark, Finland, Poland, Greece, Germany, Hungary, India, Italy, Japan, Lithuania, Turkey and the UK [3].

25th July 2019 · EPAR

NIHR

Nov 19 · Approved in EU for treatment of proliferative diabetic retinopathy (PDR) in adults [13].

Sep 19 · Recommended for EU approval by CHMP - the additional indication is treatment of proliferative diabetic retinopathy (PDR) in adults [12].

Dec 18 · Pre-registration in EU [11].

Mar 18 · FDA approves Lucentis 0.3 mg prefilled syringe (PFS) for treatment of all forms of diabetic retinopathy. The FDA granted priority review for treatment of diabetic retinopathy without diabetic macular oedema based on results from the PIII Protocol S trial [7,8].

Feb 15 · Approved in the US to treat diabetic retinopathy in patients with diabetic macular oedema. Approval is based on two PIII studies involving 759 participants who were treated and followed for three years. Patients injected with Lucentis showed significant improvement in the severity of their DR at two years compared to patients who did not receive an injection [5].

Dec 14 · FDA assigns ranibizumab breakthrough therapy status as a treatment for diabetic retinopathy [4].

Oct 14 · US FDA has accepted the supplemental Biologics License Application (sBLA) and granted Priority Review of ranibizumab for the treatment of diabetic retinopathy. The FDA confirmed action date is February 6, 2015.

Aug 14 · Genentech submits a supplemental Biologics License Application for ranibizumab to the US FDA for treatment of diabetic retinopathy. The submission is based on results of the RISE and RIDE sham treatment-controlled Phase III trials [1].

In pts with type 1 diabetes, proliferative retinopathy affects about 40% after 20 years. Maculopathy affects 10-20% of pts. In type 2 diabetes, these changes may be found at diagnosis because subclinical hyperglycaemia may have been present for a prolonged preceding period. Over 25 years, there is a significant cumulative rate of progression to diabetic retinopathy (83%), to diabetic macular oedema (29%) and clinically significant macular oedema (17%) [2].

Nov 18 · Other trials being used in support of the EU licence application will be the completed PIII REVEAL and RESTORE trials. The PIII REVEAL trial assessed ranibizumab 0.5mg as adjunctive therapy to laser photocoagulation and/or monotherapy in 390 Asian patients with visual impairment due to DMO, from China, Hong Kong, Japan, South Korea, Singapore and Taiwan (NCT00989989). The PIII RESTORE trial of ranibizumab in 345 patients with visual impairment due to DMO (NCT00687804) was conducted in Australia, Belgium, Canada, France, Germany, Greece, Hungary, Italy, Netherlands, Spain, Switzerland, Turkey and the UK. The study was designed to confirm the efficacy and safety of intravitreal injections of ranibizumab 0.5mg as adjunctive therapy to laser photocoagulation and/or monotherapy. The primary endpoint was the mean change in BCVA from baseline to the average level from months 1-12. One-year results were presented in May 2010. The study met its primary endpoint (both ranibizumab arms p < 0.0001 vs laser alone). An open-label 2-year extension of the RESTORE trial evaluating individualised ranibizumab treatment in 240 patients was completed in April 2012; favourable results have been reported (NCT00906464) [6,7].

Nov 18 · Lucentis is currently licensed in the EU for treatment of visual impairment due to diabetic macular oedema [10].

Feb 18 · PIII Protocol S trial to compare ranibizumab treatment with panretinal laser treatment in 305 patients with proliferative diabetic retinopathy, with and without diabetic macular oedema, completes in the US (NCT01489189) [9].

Oct 14 · RISE and RIDE were two identical phase 3 studies (n=759). Pts randomised to receive monthly treatment with 0.3 mg or 0.5 mg ranibizumab or sham injection. The primary objective was to evaluate the safety, tolerability and efficacy of ranibizumab in DME patients as measured by the primary efficacy endpoint of percentage of subjects gaining = 15 letters in best corrected visual acuity (BCVA) score compared with baseline at 24 months. At Month 24, an exploratory analysis demonstrated a higher proportion of patients treated with ranibizumab had observed a three-step or more improvement of their disease compared to sham, as determined by color fundus photography.The benefits of ranibizumab treatment achieved at Month 24 were maintained through Month 36 [3].

Oct 14 · The US FDA submission is based on results of the RISE and RIDE Phase III trials in which meaningful improvements in the disease were observed in a clinically significant proportion of diabetic retinopathy patients treated with ranibizumab at two years compared to patients treated with sham injections (control group). Benefits of ranibizumab treatment were maintained during year three of treatment. The safety in the RISE and RIDE Phase III trials was consistent with previous studies [3].

EPAR

NIHR

SMC

About 1 in 100 people aged 65-75, and about 1 in 8 people aged over 85 have ARMD severe enough to cause serious visual loss. About twice as many women over the age of 75 have ARMD compared with men of the same age [3]. The wet (neovascular) form is less common but results in more serious loss of vision. the incidence of wet AMD in England is around 4.8% of those aged over 65 [4].

The estimated prevalence of AMD in the UK is 4.8% of those over 65 years of age and 12.2% of those aged 80 years or more. There are around 70,000 new diagnoses in the UK each year. About 10% of all cases have wet (neovascular) AMD. Wet AMD accounts for about 60% of advanced AMD [1].

The estimated prevalence of AMD in the UK is 4.8% of those over 65 years of age and 12.2% of those aged 80 years or more. There are around 70,000 new diagnoses in the UK each year. About 10% of all cases have wet (neovascular) AMD. Wet AMD accounts for about 60% of advanced AMD [1].

About 1 in 100 people aged 65-75, and about 1 in 8 people aged over 85 have ARMD severe enough to cause serious visual loss. About twice as many women over the age of 75 have ARMD compared with men of the same age [1]. The wet (neovascular) form is less common but results in more serious loss of vision. the incidence of wet AMD in England is around 4.8% of those aged over 65 [2].