Breakthrough Clinical Results

The US Food and Drug Administration (FDA) has approved Roche's Susvimo (ranibizumab injection) 100 mg/mL for treating diabetic retinopathy (DR). Susvimo, a refillable eye implant, delivers continuous ranibizumab, a VEGF inhibitor, offering a less frequent treatment option compared to monthly injections. The approval is based on positive results from the Phase III Pavilion study, showing superior improvements in DR severity and no need for supplemental treatment at one year. Susvimo is now available to US retina specialists and their patients with DR who have previously responded to at least two anti-VEGF injections. This is the third FDA approval for Susvimo, which is also approved for treating wet age-related macular degeneration and diabetic macular edema.

Incidence and Prevalence

Global Estimates of Diabetic Retinopathy Incidence and Prevalence

Based on PubMed data, diabetic retinopathy prevalence varies significantly across different populations worldwide:

• In the United States:

• 11% overall prevalence in general population studies

• 36% prevalence among people with diagnosed diabetes

• 20.3% prevalence in elderly populations (ages 69-102)

• 2.7% have proliferative retinopathy

• 2.1% have macular edema

• In Europe:

• 26.2% prevalence in North East Italy

• 24.4% with background retinopathy

• 1.8% with proliferative retinopathy

• 18% prevalence in diabetic patients in the upper Rhine region of France

• 1.5% have proliferative or serious nonproliferative forms

• In Asia:

• 26.6% prevalence in a study of 1,228 type 2 diabetic patients in Iran

• 18% prevalence in rural Korean patients with type 2 diabetes

• 5.0% with proliferative or severe non-proliferative forms

• 6.2% prevalence in newly diagnosed type 2 diabetes patients

• In South America:

• 35.7% prevalence in Brazilian patients with type 1 diabetes

• 12% have vision-threatening diabetic retinopathy

Key Risk Factors

Multiple studies have identified important risk factors for diabetic retinopathy:

• Duration of diabetes:

• 17.3% prevalence for patients with <5 years duration

• 60.8% prevalence for patients with >20 years duration

• Proliferative retinopathy is more prevalent after 20 years of diabetes

• Poor glycemic control (higher HbA1c levels)

• Diabetes type:

• Higher prevalence in Type 1 diabetes

• Higher in insulin-treated Type 2 compared to non-insulin-treated Type 2 diabetes

• Hypertension (both systolic and diastolic)
• Racial differences: higher prevalence in black people compared to white people
• Higher serum uric acid levels
• Elevated fasting and post-prandial glucose levels
• Family history of diabetes

These findings highlight the global burden of diabetic retinopathy and emphasize the importance of early detection and management of both diabetes and its complications, particularly in high-risk populations with multiple risk factors.

Drug used in other indications

Susvimo (Ranibizumab Injection) Trials

Based on the provided context, there is no information available about Susvimo (ranibizumab injection) being trialled for indications other than Diabetic Retinopathy.

The context does not contain any specific data about: - Ongoing clinical trials for Susvimo - Indications being investigated for Susvimo beyond Diabetic Retinopathy - Intervention models for Susvimo trials

While the context mentions ranibizumab (the active ingredient in Susvimo) being used for various conditions such as: - Retinal Vein Occlusion (RVO) - Macular edema secondary to central retinal or hemiretinal vein occlusion - Wet age-related macular degeneration

These references discuss standard ranibizumab formulations rather than the Susvimo delivery system specifically.

The context also mentions studies involving bevacizumab and aflibercept for similar conditions, but does not provide information about Susvimo-specific trials or intervention models.

Study Design Parameters

Study Design Parameters and Endpoints in Key Diabetic Retinopathy Trials

Study Design Parameters

Diabetic retinopathy trials have employed various study designs including: - Prospective, consecutive, controlled, observational study - Prospective cohort study - Three-armed double-blind randomized clinical trial - Longitudinal study - Hospital-based trial case - Retrospective review

Patient classification systems commonly utilized: - Early Treatment Diabetic Retinopathy Study Group (ETDRS) criteria - International clinical DR disease severity scale - Classification into nonproliferative and proliferative diabetic retinopathy

Sample sizes and participant characteristics varied across studies: - 40 patients (30 diabetic patients in 3 groups of 10, 10 controls) - 30 patients with DR due to type 2 diabetes - 88 patients (44 in experimental group with 52 eyes, 44 in control group with 54 eyes) - 25 patients with 41 eyes - 123 eyes with center-involving DME - 80 eyes of 40 patients with type 1 DM and no/minimal DR - One study analyzed data from 30 UK NHS hospital trusts covering 307,538 patients (76,127 with diabetes)

Treatment interventions investigated included: - Intravitreal ziv-aflibercept (2.5mg and 1.25mg) vs. intravitreal bevacizumab (1.25mg) - Cataract surgery vs. laser photocoagulation - Intravitreal bevacizumab (Avastin) 1.25mg (0.05ml) - Ranibizumab intravitreal injections - SML laser treatment compared to intravitreal ranibizumab

Study Endpoints

Key trials employed various endpoints and measurements:

Visual Function Measurements: - Best-corrected visual acuity (BCVA) was a primary endpoint in multiple studies - Full-field maximal and photopic cone ERGs with analysis of amplitudes and implicit times

Anatomical Measurements: - Central macular thickness (CMT) - Retinal layer thickness measurements (RNFL, GCL, IPL) - Intraocular pressure

Imaging and Diagnostic Methods: - Spectral-domain optical coherence tomography (SD-OCT) - Color Doppler imaging (CDI) - Optical coherence tomography (OCT) - Colour fundus photography (CFP) - Fundus photography and ophthalmoscopy

Biochemical Markers: - Fatty acid composition of erythrocyte membrane - Biomarker levels in serum and vitreous - Resistivity index (RI) of central retinal artery - VEGF plasma levels measured by ELISA - AGE levels in ocular fluid

Some trials included follow-up assessments at specific intervals (1 week, 3 months, 6 months) to evaluate the durability of treatment effects and progression of diabetic retinopathy.