New Indication Filed for Ranibizumab for Treatment of Retinopathy of Prematurity

Despite marginally missing statistical significance for the primary endpoint in its phase 3 clinical trial, Novartis has decided to file for a new indication for ranibizumab (marketed as Lucentis), a potential treatment for premature infants with retinopathy of prematurity (ROP), a rare disease but leading cause of childhood blindness.

"The RAINBOW study is part of our ongoing commitment to addressing the most urgent needs in eye care,” said professor Andreas Stahl, MD, senior physician in retinal surgery and head of the Angiogenesis Research Group at the Eye Center at the University of Freiburg, Germany, in a recent statement.

“We look forward to filing outside the United States for an indication in ROP, which may bring us one step closer to reimagining care for these premature infants," Dirk Sauer, development unit head at Novartis Ophthalmology, added.

In the RAINBOW phase 3 clinical trial comparing ranibizumab with laser eye surgery, investigators set out to determine if intravitreal ranibizumab was superior to laser ablation therapy in the treatment of patients with ROP.

The trial consisted of 3 treatment arms; one arm was administered 1 intravitreal injection of ranibizumab, .2 mg in both eyes on day 1 (baseline), with up to 2 re-treatments allowed for each eye if required, while the other experimental arm was administered 1 intravitreal injection of ranibizumab, .1 mg in both eyes on day 1 (baseline), with up to 2 re-treatments allowed for each eye if required. The active comparator arm was administered laser treatment to each eye on day 1 (baseline) with supplementary treatments allowed.

Upon analysis, clinical relevance was observed with ranibizumab as a treatment for ROP, despite marginally missing statistical significance for the primary endpoint (p=.0254, as opposed to the significance level of p=.025); the difference in treatment success with ranibizumab at doses of .1mg and .2mg was 75% and 80%, respectively, compared with 66.2% for laser surgery, the current standard of care.

Due to these positive findings, Novartis has decided to proceed with filing ex-US for a new indication for ranibizumab as a treatment for ROP.

"Laser surgery, the current standard of care, works by destroying the tissue in the eye that contributes to the elevation of VEGF,” Dr. Stahl explained in the statement. “While it is an effective treatment, there is a clear unmet need for innovative ways to treat ROP without destroying retinal tissue. Lucentis demonstrated in the RAINBOW study that it is an efficacious and well-tolerated option for the treatment of ROP that may offer new hope to parents of this vulnerable patient population."

By pharmacologically targeting and reducing the elevated intraocular level of vascular endothelial growth factor (VEGF), ranibizumab addresses the underlying cause of the condition. Unlike ranibizumab, laser surgery destroys diseased retinal tissue responsible for elevated vascular endothelial growth factor (VEGF).

ROP is a disorder characterized by childhood vision loss in both eyes, leading to lifelong visual impairment and blindness. Premature infants born before 31 weeks of gestation (38 to 42 weeks of gestation is a full-term pregnancy) and weighing 2 ¾ pounds (1250 grams) are primarily affected. Complications, such as retinal detachment, myopia (nearsightedness), strabismus, amblyopia, and glaucoma, can also occur in these patients.