Novartis' VEGF Inhibitor Ranibizumab Gains New NMPA Approvals for ROP and Diabetic Retinopathy

Source: PharmaCube Info

Author: Sunshine

On August 16, the official website of the National Medical Products Administration (NMPA) showed that the marketing authorization application for a new indication of Novartis’s ranibizumab (Acceptance No.: JXSS2000038/44/45/46/47) has been approved, reportedly for the treatment of retinopathy of prematurity and diabetic retinopathy (DR).

Retinopathy of prematurity is the leading cause of blindness in premature infants. It is a rare, potentially blinding disease caused by abnormal development of retinal blood vessels in preterm infants. Vascular endothelial growth factor (VEGF) is a key regulator of new blood vessel development (known as angiogenesis) and plays a critical role in the progression of retinopathy of prematurity; if the blood vessels fail to develop normally, they may exert traction on the retina, leading to macular traction, retinal detachment, or other structural abnormalities that may result in vision loss or even blindness.

Diabetic retinopathy (DR) refers to a series of characteristic lesions caused by retinal microvascular damage due to diabetes. It is one of the most common and severe ocular complications in patients with diabetes, as well as a chronic progressive disease that impairs vision and can even lead to blindness. Based on disease severity, DR is primarily classified into non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). In China, there are approximately 130 million patients with diabetes, among whom over 30 million are affected by diabetic retinopathy, with a risk of blindness 25 times higher than that of the general population. The prevalence of DR is approximately 34.6%, and that of PDR is about 7%, making it the leading cause of blindness worldwide.

PDR is a more severe, vision-threatening type of diabetic retinopathy (DR). At this stage, circulatory impairment leads to retinal hypoxia, triggering the growth of fragile new blood vessels into the retina and vitreous (the gel-like fluid that fills the posterior segment of the eye). Blood from these neovascular vessels may leak into the vitreous, resulting in blurred vision.

Initially, DR may be asymptomatic or cause only mild vision loss, but over time, it progresses from non-proliferative DR (NPDR) to vision-threatening PDR. Approximately 50% of patients with severe NPDR progress to PDR within 1 year, and 25% of patients develop PDR within 15 years of diabetes onset.

Ranibizumab is a VEGF (vascular endothelial growth factor) inhibitor developed by Roche, with a relatively small molecular weight of only 48 kDa. Its primary mechanism of action involves binding to and blocking VEGF receptors, thereby reducing vascular endothelial cell proliferation, vascular leakage, and neovascularization, while promoting the regression of existing neovascular vessels. It is the first anti-VEGF drug approved globally for ophthalmic use.

In 2003, Roche and Novartis entered into an agreement whereby Roche retained the rights to commercialize ranibizumab in the United States, while Novartis held exclusive commercialization rights in the rest of the world.

Data from the PharmaCube NextPharma database shows that ranibizumab has been approved globally for six major indications: wet age-related macular degeneration; diabetic retinopathy; macular edema secondary to retinal vein occlusion; myopic choroidal neovascularization; retinopathy of prematurity; diabetic macular edema.

In China, ranibizumab has been approved for four indications, namely: wet age-related macular degeneration (wAMD); diabetic macular edema (DME); visual impairment due to macular edema secondary to retinal vein occlusion (RVO) (branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)); and treatment of visual impairment due to choroidal neovascularization (CNV, i.e., CNV secondary to pathological myopia (PM) and other causes).

Since its market launch in 2006, ranibizumab has maintained global sales at approximately US$3 billion. In 2014, global sales peaked at over US$4 billion.

Novartis Sales

Roche Sales

It is worth noting that the global patent for ranibizumab will expire in the coming years. Many companies in China are actively developing me-too drugs or biosimilars, while Novartis’s next-generation ophthalmic drug, Beovu, is currently in Phase III clinical trials in China.