FDA approval of Lucentis (ranibizumab injection) 0.3 mg to treat diabetic retinopathy (DR) in patients with diabetic macular edema (DME) gives the longstanding eye treatment breathing room in an increasingly crowded ophthalmologic market.

Lucentis, a vascular endothelial growth factor (VEGF) inhibitor developed by Genentech Inc., a unit of Roche AG, of Basel, Switzerland, initially was approved by the FDA in 2006 to treat neovascular age-related macular degeneration (wet AMD), later adding macular edema following retinal vein occlusion. In 2012, the agency elevated the drug to blockbuster status with approval to treat DME, offering patients the first improvement on standard-of-care in 25 years. (See BioWorld Today, July 5, 2006, and Aug. 13, 2012.)

The drug now becomes the first eye medicine approved to treat the additional indication, gaining the nod with a breakthrough therapy designation and priority review based on results from the RISE and RIDE phase III trials.

The studies involved 759 participants with baseline DR severity scores ranging from 10 to 75 in the study eye on the ETDRS diabetic retinopathy severity scale who were treated and followed for three years. Secondary and exploratory outcomes evaluated at 24 months showed a higher proportion of patients treated with Lucentis observed a three-step or better improvement in DR compared to sham, as determined by color fundus photography.

Safety in the trials was consistent with previous studies, with the most common side effects including bleeding of the conjunctiva, eye pain, floaters and increased intraocular pressure. Serious side effects included endophthalmitis and retinal detachments.

With diabetes reaching near epidemic status in the U.S. – more than 29 million people diagnosed with type 1 or type 2, according to the Centers for Disease Control and Prevention – DR has become the most common diabetic eye disease in the country and the leading cause of blindness in adults ages 20 to 74.

In 2008, 33 percent of adults with diabetes ages 40 or older had some form of DR. In some cases of DR with DME, abnormal blood vessels grow on the surface of the retina, causing severe vision loss or blindness if they break.

The approval comes none too soon for the Lucentis franchise, which is near the top of its sales curve, projected to peak at $4.3 billion in 2017, according to Cortellis Competitive Intelligence, before falling rapidly as the drug faces patent expiry after 2020. More than a decade ago, Novartis AG, also of Basel, inked a deal with Genentech Inc. for rights outside North America to the therapy in wet AMD, where it still shares in the handsome revenue stream. (See BioWorld Today, June 26, 2003.)

Lucentis is staring down a range of competitors. In AMD, the drug already is fending off lower-cost off-label use by Avastin (bevacizumab, Genentech Inc./Roche AG) – a topic that has escalated in Europe with pressure to allow such treatments – and by the approved Eylea (aflibercept, Regeneron Pharmaceuticals Inc.), partnered outside the U.S. with Bayer AG, of Leverkusen, Germany. (See BioWorld Today, Aug. 7, 2013, June 13, 2014, and July 16, 2014.)

Other biotechs also are taking aim at the eye disease space. Last year, after multiple rejections, Alimera Sciences Inc., of Atlanta, received the green light from the FDA for its Iluvien implant, indicated for DME in patients previously treated with a course of corticosteroids who did not have a clinically significant rise in intraocular pressure. The company licensed Iluvien – which was approved in Europe in 2012 – from Psivida Corp., of Watertown, Mass. (See BioWorld Today, Sept. 30, 2014.)

Aerpio Therapeutics Inc., of Cincinnati, continues to advance AKB-9778, a human protein tyrosine phosphatase-beta inhibitor designed to stabilize vasculature and to activate the Tie2 receptor to treat DME. (See BioWorld Today, Oct. 5, 2012.)

Tarrytown, N.Y.-based Regeneron holds a stake in Avalanche Biotechnologies Inc., whose candidate, AVA-101, is a gene therapy targeting VEGF to treat wet AMD. (See BioWorld Today, May 6, 2014.)

And that's not to mention co-formulation therapies. Ophthotech Corp.'s Fovista, an antiplatelet-derived growth factor agent designed to enhance the efficacy of anti-VEGF therapies in wet AMD, last year attracted a potential $1 billion-plus ex-U.S. deal with Novartis. And last week, Ohr Pharmaceutical Inc., of New York, raised $25 million to fund dual pivotal phase III studies of its Lucentis-boosting eye drops, OHR-102 (squalamine), in newly diagnosed patients with wet AMD. (See BioWorld Today, May 20, 2014, May 21, 2014, and Feb. 9, 2015.)

Another threat comes from a biosimilar candidate, PF582, from San Diego-based Pfenex Inc., which is seeking its first approval in wet AMD, with a phase III trial expected to begin this year. The company completed an IPO last year to finance the compound's remaining development program and early commercialization. (See BioWorld Today, June 9, 2014.)

In a research note, Jefferies LLC analyst Biren Amin wrote Monday that anti-VEGF competition targeting Lucentis could heat up this year with several more programs moving into phase III, including conbercept, an anti-VEGF from Chinese biotech Chegdu Kanghong Biological Science & Technology Co., and abicipar (formerly Darpin) from Actavis plc, of Dublin.