FDA Approves Genentech's Susvimo for Diabetic Retinopathy

Genentech announced FDA approval of Susvimo (ranibizumab injection) 100 mg/mL for treating diabetic retinopathy (DR). Susvimo, delivered via a Port D...

Breakthrough Clinical Results

Genentech announced FDA approval of Susvimo (ranibizumab injection) 100 mg/mL for treating diabetic retinopathy (DR). Susvimo, delivered via a Port Delivery Platform implant, offers a less frequent treatment option compared to monthly injections. The approval is based on positive results from the Phase III Pavilion study, showing superior vision maintenance with one refill every nine months. Susvimo is already approved for wet age-related macular degeneration and diabetic macular edema.

Key Highlights

FDA approves Susvimo for diabetic retinopathy.
Susvimo provides continuous drug delivery via an implant, requiring refills only every nine months.
Positive Phase III Pavilion study results demonstrated superior vision maintenance compared to monthly anti-VEGF injections.
Susvimo is the first and only FDA-approved continuous delivery treatment for DR.

Incidence and Prevalence

Global Estimates of Diabetic Retinopathy Incidence and Prevalence

Diabetic retinopathy represents a significant global health concern, particularly as diabetes rates continue to rise worldwide. Based on available data, the prevalence of diabetic retinopathy varies considerably across different populations and regions.

Regional Prevalence Rates

In the U.S. National Health and Nutrition Examination Survey (2005-2006), diabetic retinopathy had an 11% overall prevalence, with a much higher 36% prevalence specifically among people with diagnosed diabetes
A cross-sectional study of 1228 type 2 diabetic patients in a diabetes referral clinic (2012) found a prevalence of 26.6%
A population-based study in the Veneto region of North East Italy reported a 26.2% prevalence, with 24.4% having background retinopathy and 1.8% showing proliferative retinopathy
Among rural Korean patients with type 2 diabetes (2005-2006), the overall prevalence was 18%, with 5.0% having proliferative or severe non-proliferative forms
In Warsaw regional Diabetes Center, 31.4% of 1334 type 2 diabetic patients had diabetic retinopathy, with 1.3% showing proliferative retinopathy
The Jackson Heart Study of African Americans found diabetic retinopathy in 9.4% of participants with impaired fasting glucose and 32.4% in those with type 2 diabetes

Progression and Risk

Almost all patients with type 1 diabetes will develop retinopathy over a 15-20 year period, with approximately 20-30% advancing to the blinding stage
Greater than 60% of patients with type 2 diabetes will develop retinopathy over time

Global Impact

Diabetic retinopathy remains the most common cause of vision impairment in people of working age in Western society
With the global epidemic of type 2 diabetes, over 360 million people are projected to suffer from diabetes and its complications by 2030

The varying prevalence rates across different populations highlight the importance of considering regional and demographic factors when addressing diabetic retinopathy. These differences may reflect variations in healthcare access, diabetes management practices, genetic factors, and other population-specific characteristics.

Study Design Parameters

Study Design Parameters and Endpoints in Key Trials for Diabetic Retinopathy

Early Treatment Diabetic Retinopathy Study (ETDRS)

Multicenter randomized clinical trial with 3711 patients
Patients had mild to severe nonproliferative or early proliferative diabetic retinopathy
Assessed effects of photocoagulation and aspirin (650 mg/d)
Randomization: patients assigned to aspirin or placebo groups; one eye randomly assigned to early photocoagulation, other eye to deferral
Outcomes measured through annual seven standard stereoscopic field fundus photographs
Clinical examinations every 4 months
Found aspirin did not increase occurrence, severity, or duration of vitreous/preretinal hemorrhages

Non-mydriatic Camera/AI Study

Clinical study at Akdeniz University with 900 volunteer diabetic patients without diagnosed retinopathy
Compared three non-mydriatic fundus cameras with EyeCheckup AI software
Patients underwent dilation and 4 wide-field fundus photography
Three retina specialists graded images using American Academy of Ophthalmology standards
Pre-registered on clinicaltrials.gov (NCT04805541)
Evaluated sensitivity and specificity for diagnosing more than mild DR, vision-threatening DR, and clinically significant diabetic macular edema

Diabetic Pre-retinopathy Study

Two-year study (2018-2019) at Teaching Hospital Kralovske Vinohrady in Prague
54 patients aged 17-42 years with T1DM duration of 12-35 years
Examined 106 eyes using three methods: contrast sensitivity (CS), spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography-angiography (OCT-A)
Identified intermediate stage between normal retina and DR called diabetic pre-retinopathy (DpR)

Biomarker Study

Prospective, consecutive, controlled, observational study (June 2018-January 2020)
Collected blood and vitreous samples on day of vitrectomy
Compared biomarker levels between diabetic and non-diabetic patients
Measured biomarkers including transthyretin, erythropoietin, interleukins, and other inflammatory markers
Analyzed relationship between biomarker levels and DR severity

Resistivity Index Study

Examined type II diabetics using ETDRS classification system
Grouped patients into: No DR, Nonproliferative DR, and Proliferative DR
Used SD-OCT imaging and ultrasonic color doppler imaging
Measured resistivity index (RI) of central retinal artery
Compared RI between groups and studied association with OCT biomarkers
Included 56 eyes of 28 patients (20 in Group A, 14 in Group B, 22 in Group C)

Cataract Surgery Study

88 patients with DR (December 2019-December 2020)
Split into experimental group (44 patients/52 eyes) and control group (44 patients/54 eyes)
Experimental group received cataract surgery; control group received laser photocoagulation
Measured central macular thickness and visual acuity
Also assessed VEGF levels and complication rates

Drug used in other indications

Based on the provided context information, Susvimo (ranibizumab injection) is being trialled for central retinal vein occlusion (CRVO) in addition to diabetic retinopathy.

The intervention model for the CRVO trial is: - An ongoing, prospective, open-label, single-center, uncontrolled study involving 10 adult patients with macular edema associated with perfused CRVO - Patients received 3 monthly intravitreal (IVT) injections of either 0.3 or 0.5 mg ranibizumab (n=5 at each dose) - Additional injections were administered quarterly as needed over the ensuing 21 months at the physician's discretion for recurrent or persistent macular edema

The trial demonstrated that after 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients, respectively, gained ≥15 letters in best-corrected visual acuity (BCVA). Mean BCVA improved by 12±20 letters, 3±21 letters, and 1±24 letters at 3, 6, and 9 months respectively, compared with baseline.

Central retinal thickness (CRT) showed a mean decrease of 272±244 μm, 88±178 μm, and 119±153 μm at 3, 6, and 9 months compared with baseline. No significant differences were observed between the 0.3-mg and 0.5-mg doses.

Most patients experienced decreases in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head swelling at months 3 and 6 compared with baseline. No patients progressed to ischemic CRVO or experienced a severe adverse event attributed to ranibizumab.

The study found that ranibizumab was generally well-tolerated and improved BCVA and decreased CRT. However, the improvements observed during the initial monthly injection period (0 to 3 months) were possibly lost during the quarterly treatments (3 to 9 months).