Lucentis is on the march. Again.
Last week, Genentech Inc. released the detailed data from the Phase III MARINA study of Lucentis (ranibizumab) in wet age-related macular degeneration, confirming interim data disclosed in May - but the news got even better.
Earlier, 95 percent of patients were said to have lost less than 15 letters of visual acuity compared to placebo patients (the primary endpoint). According to the full data, the difference was 17 letters. That is, patients given Lucentis gained 7 letters, whereas those given placebo lost 10.5 letters after a year of treatment. And the effects were the same in patients given 0.3 mg and 0.5 mg.
Twenty-five percent of the lower-dose patients and 34 percent of the higher-dose patients improved vision by more than 15 letters, compared to 5 percent of the control group. A satisfying 40 percent of the treated patients scored 20/40 or better in visual acuity compared to 11 percent in the control.
Analysts are starting to look more fondly upon Lucentis.
Eyetech Pharmaceuticals Inc. has been through it all before, and not long ago.
Fairly or not, Eyetech, which markets the aptamer Macugen, developed with Pfizer Inc., for AMD lost 45 percent of its value when the first MARINA data became public. Macugen boosters were quick to point out that Genentech's trial was not a head-to-head study, and patients tested by Genentech had minimally classic or occult AMD, whereas Macugen has been tested and approved for all subtypes of the disease. (See BioWorld Financial Watch, June 6, 2005.)
There's more to come from Lucentis. Phase III data from the ANCHOR trial, testing 423 patients with predominantly classic wet AMD who are getting either Lucentis or Visudyne, are due in the last quarter of this year. Another trial, called PIER, is evaluating reduced dosing - three monthly injections of Lucentis, followed by shots every three months after. Results from that study are expected in the first half of next year. PIER is designed to silence critics who charge that Lucentis is less convenient than Macugen.
Also, Eyetech pointed out, the study of Macugen welcomed every kind of patient, while Genentech examined subtypes. Further, patients in the Lucentis control arm showed an impressive 62 percent rate of maintained vision, though none of the Lucentis patients had been given the photodynamic therapy Visudyne (verteporfin) from QLT Inc. and Novartis AG, unlike some patients in Macugen's trial.
Lucentis, like Macugen (pegaptanib sodium), is designed to bind and inhibit vascular endothelial growth factor-A, but the Genentech drug binds to all five VEGF isoforms, whereas Eyetech's compound binds only to the 165 isoform - and that, Eyetech insists, is the way to attack AMD.
There was more AMD news early this month, when Pharmacopeia Drug Discovery Inc. partnered its preclinical lead compounds for ocular disease with Allergan Inc. in a deal focused on compounds that target angiogenesis and might be used alone or in combination with VEGF inhibitors. Under the terms, Pharmacopeia gets cash up front, with preclinical and clinical milestone payments, as well as royalties on approved drugs for ophthalmology.
Others potentially to compete in the AMD space are Sirna Therapeutics Inc.'s VEGF inhibitor, Sirna-027, and Genaera Corp.'s Evizon (squalamine lactate). The latter is getting ready for a pair of Phase III trials that will evaluate the compound for choroidal neovascularization associated with AMD. Evizon is said to selectively block all subtypes of VEGF, as well as other growth factors tied to angiogenesis. Also, in May, Alcon Inc. got an approvable letter for Retaane (anecortave acetate suspension) for AMD, and the company said it will be meeting with the FDA to determine the next steps.
But, for now at least, Lucentis seems to be stealing the show in the AMD market, estimated at about $600 million. The latest data "suggest Lucentis to be potentially more effective than other competing AMD therapies (although exacting comparisons are difficult to draw across varied trial designs and disease severity)," wrote Jennifer Chao, analyst with Deutsche Bank, in a research note.
Christopher Raymond, analyst with Robert Baird & Co., also sounded sanguine on Lucentis, saying his firm "[foresees] a dominant market share for this product."
Jason Napodano, analyst with Zacks Equity Research, in early July declared Macugen's dosing advantage "with Pfizer's marketing muscle and a two-year time-to-market benefit leads us to believe that Macugen will achieve our bullish sales forecasts," and a "recent upward revision in Macugen sales guidance for 2005 forecast supports our view." But later in the month, writing about Genentech, Napodano said "positive Lucentis Phase III MARINA and FOCUS trial data look superior to [data for] Eyetech's Macugen." More Phase III results "should confirm this data by year's end or early 2006," he wrote, and Genentech is likely to garner "yet another priority review from the FDA."
The company likely will use data from the just-reported MARINA study and the ANCHOR trial to file for approval of Lucentis, which observers say could come as early as the end of this year.
"It does look quite good," Howard Liang, analyst with A.G. Edwards, told BioWorld Financial Watch of the Lucentis data. He predicted the drug would win "a majority of the market share in one to two years" after launch.
Meanwhile, rumors buzz that Pfizer will take over Eyetech so that the pharmaceutical giant can hang onto all the Macugen profits. Pfizer has been in a buying mood of late, most recently disclosing its plan to take over Vicuron Pharmaceuticals Inc. for $29.10 per share, or about $1.9 billion, a 74 percent premium over the firm's 90-day average closing price and 21 percent higher than the highest historical closing price.
Pfizer made public in February its plan to buy out Idun Pharmaceuticals Inc. for an undisclosed amount, and a month before that entered an agreement to pay up to $527 million for Angiosyn Inc.
Liang, who maintains a "hold" rating on Genentech's stock, allowed that Eyetech and Pfizer can still make a case for their drug, at least until more Phase III data are disclosed in the fourth quarter. But he found convincing the Lucentis results already in hand.
"It's always difficult to compare different trials, but you get a sense that Lucentis is efficacious," he said. "We just haven't seen this kind of data [before]."