Genentech Inc.says U.S. physicians can order Lucentis (ranibizumab) at a 0.3 mg monthly dose for diabetic macular edema immediately and product will start shipping Aug. 15, following FDA’s Aug. 10 approval for this indication.

A recombinant humanized monoclonal antibody fragment, Lucentis is now the first FDA-approved medicine for diabetic macular edema, a sight-threatening complication of diabetes. This marks the third approved indication for the drug, after wet age-related macular degeneration and macular edema.

[Editor’s note: This story was updated to include a correction that Lucentis and Avastin are derived from the same mouse monoclonal antibody. A previous version said ranibizumab derived from bevaciziumab]

Approval of the VEGF inhibitor was widely expected after a vote in favor of clearance by FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee in late July, where the discussion focused more on dose selection than efficacy or safety concerns ([A#00120730009]). The 0.3 mg and 0.5 mg doses looked similar in terms of efficacy and questions arose about whether there was a dose-dependent differential when it came to adverse events. One option on the table was approval of different labels for the two different doses. In the end, the panel voted 10-0 in favor of the 0.3 mg dose and 8-2 for a 0.5 mg dose.

Lucentis Indications And Sales

U.S. Approved Uses

Diabetic Macular Edema (0.3 mg monthly), August 2012

Macular Edema Following Retinal Vein Occlusion (0.5 mg monthly), June 2010

Wet Age-related Macular Degeneration (0.5 mg monthly), June 2006

World Sales, 2011 (% change from 2010)

Roche, U.S.: $1.5 billion (+23%)

Novartis, ex-U.S: $2 billion (+34%)

An estimated 560,000 people in the U.S. have DME, a swelling of part of the retina that can cause leaky blood vessels, blurred vision and severe vision loss. About 10% of people with diabetes – an enormous patient population – are likely to get DME. Up to now, there haven’t been any approved medications, though steroids and VEGF inhibitors like Avastin are used off-label. Laser treatment is FDA-approved for the condition and can be used to stabilize vision, but unlike VEGF inhibitors, has not demonstrated improvements in sight.

Importantly, Lucentis’ new label provides FDA’s stamp of approval that the drug has been thoroughly analyzed in DME trials, though it remains to be seen whether this will give the drug a commercial edge relative to lower-priced unofficial options.

The BLA for Lucentis was supported by RISE and RIDE, identical placebo-controlled, three-year studies in a total of 759 patients. Those on Lucentis demonstrated significant and sustained improvements in vision compared to placebo. No additional efficacy benefit was reported for the higher dose.

The trial results got a good reception upon release at the American Diabetes Association meeting in mid-2011, particularly considering practical impact; for example, the sight improvements made with the drug could allow patients to drive. Even back then, however, some clinicians were questioning the expense in this indication, since Genentech’s Avastin (bevacizumab) could be used off-label at a dramatically lower price Also see "Lucentis Shines In Diabetic Eye Disease, But Competition Looms From Cheap, Off-Label Avastin" - Pink Sheet, 28 June, 2011..

Ranibizumab and bevacizumab are derived from the same mouse monoclonal antibody.

Questions still remain about whether Lucentis is differentiated in DME from Avastin and Regeneron’s VEGF inhibitor Eylea (aflibercept), which was approved in November 2011 for wet AMD Also see "Challenging Lucentis: Eylea’s Early Progress Prompts $250 Mil.-$300 Mil. Sales Forecast For 2012" - Pink Sheet, 16 February, 2012..

In March, discussion at the Medicare Evidence Development and Coverage Advisory Committee suggested that the relative efficacy and safety between intravitreal anti-VEGF drugs cannot be determined, as currently head-to-head data in DME is not available and what data is available indicates equivalence Also see "Avastin, Lucentis Assumed Comparable In DME Absent More Data, MEDCAC Members Say" - Pink Sheet, 26 March, 2012.. Medicare has not opened a national coverage determination for anti-VEGF agents in DME.

Lucentis has survived one major head-to-head hurdle – the CATT study, published in April 2011. Funded by the National Institutes of Health, the head-to-head trial of 1,200 patients with age-related macular degeneration concluded that Lucentis and Avastin were equivalent for visual acuity. No difference in major adverse events was reported Also see "Lucentis And Avastin Stack Up In CATT, Forcing Genentech/Novartis To Play Defense" - Pink Sheet, 28 April, 2011..

Writing in an investor update about performance in 2011, a year in which Lucentis racked up CHF $1 billion in U.S. sales (about the same in U.S. dollars), up 23% from 2010, Roche noted that the CATT study had a “limited impact on U.S. sales growth. The total Lucentis patient share in the wet AMD segment remained stable in the US through the third and fourth quarters.”

This was due in part to reports in 2011 about safety concerns related to unapproved intravitreal use of Avastin in wet AMD, Roche reported.

Novartis AG, which holds ex-U.S. rights, reported over $2 billion in sales for Lucentis in 2011, up 34% from 2010.

Genentech Says Lucentis DME Product Will Ship Shortly

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