Memorandum

FDA approves Roche/Genentech’s Lucentis (intravitreal ranibizumab) for diabetic retinopathy with DME – February 12, 2015

Executive Highlights

  • Last Friday, the FDA announced the approval of Roche/Genentech’s Lucentis (intravitreal ranibizumab) for diabetic retinopathy (DR) in patients with diabetic macular edema (DME), the first treatment approved for this indication.

Last Friday, the FDA announced the approval of Roche/Genentech’s Lucentis (intravitreal ranibizumab) for diabetic retinopathy (DR) in patients with diabetic macular edema (DME), making it the first treatment approved for this indication in the US. As of 2012, Lucentis had been FDA approved for diabetic macular edema with retinal vein occlusion but without the diabetic retinopathy aspect as part of the approval. As a reminder, the product received Priority Review status from the FDA in October; this designation (one that drugs for glucose lowering never receive) allows for expedited review of drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. The approval was supported by the strong findings of the RISE and RIDE phase 3 trials, which demonstrated significant improvements in DR severity after two years with Lucentis vs. sham injections. This decision is a major win for patients given the enormous unmet need in this area – according to data cited in the FDA press release, 33% of adults with diabetes aged 40 years or older had some form of retinopathy as of 2008. We assume the DR indication will also help bolster Lucentis’ sales in the face of increased competition in DME from Bayer/Regeneron’s Eylea (intravitreal aflibercept) and Alimera Sciences/pSivida’s Iluvien (intravitreal fluocinolone acetonide). We applaud Genentech for pursuing this expanded indication for Lucentis in an area of such great unmet need and would love to see other companies follow suit; of course, our ultimate hope is that more effective prevention and early treatment of diabetes can reduce the rates of retinopathy and other debilitating complications in the first place. 

  • The phase 3 RISE and RIDE studies demonstrated significant improvements in DR severity after two years with Lucentis vs. sham injections. The two identically designed double-blind trials enrolled a total of 759 patients with DR and DME who were randomized to receive monthly treatment with 0.3 mg Lucentis, 0.5 mg Lucentis, or a sham injection. The trials met the primary endpoint of significantly greater visual acuity gains at 24 months with Lucentis vs. sham; these results supported the approval of a DME indication for Lucentis in 2012. In addition, results showed that a significantly higher proportion of patients treated with Lucentis experienced at least a three-step improvement in DR severity scores (as measured by the ETDRS diabetic retinopathy severity scale).
  • Lucentis posted US sales of ~$1.9 billion in 2014, up 2% YOY in constant currencies from 2013. Roche management commented during the company’s 4Q14 update that the DME indication (approved in 2012) was a significant driver of growth in 2014, though the company’s outlook for 2015 is much more conservative (flat sales or even a slight decline) due to the increased competition in DME. We assume that the diabetic retinopathy indication will at least partially blunt the impact of increased competition in DME; we wonder whether Roche/Genentech’s competitors will eventually pursue a diabetic retinopathy indication for their products as well. As a reminder, Novartis markets Lucentis in most ex-US markets.
  • Diabetic retinopathy remains an area of significant unmet need. As mentioned above, the FDA press release cited data indicating that 33% of adults with diabetes aged 40 years or older had some form of retinopathy as of 2008. This is fairly consistent with the figures in the latest CDC National Diabetes Statistics Report, which showed that 28.5% of adults over 40 with diabetes had retinopathy in 2005-2008 and 4.4% had advanced retinopathy. In addition to the burden for patients, diabetic retinopathy and other ophthalmic complications contribute to significant excess costs and lost productivity, as outlined in a recent Genentech-supported study by Brook et al. We are glad to see more treatment options becoming available for these debilitating complications, though our ultimate hope is that a greater focus on prevention and early treatment of diabetes can reduce their incidence in the first place.

-- by Emily Regier, Manu Venkat, and Kelly Close