West Coast Editor

Ever on the march, Genentech Inc. rounded out the year with another regulatory move, submitting - as promised - a biologics license application for Lucentis against neovascular wet age-related macular degeneration.

"We FedExed the submission yesterday," Genentech spokeswoman Dawn Kalmar said Friday, and the FDA has 45 days after receipt to decide whether it will grant priority review, which would mean a decision within six months from the date that the BLA is logged in.

Genentech's stock (NYSE:DNA) ended the day at $92.50, up 44 cents.

"We've put six years of rigorous clinical study into getting us where we are today," Kalmar said, noting that the company's results with anti-VEGF Lucentis (ranibizumab) in Phase I trials proved so impressive that researchers went directly into Phase III and, from there, "pulled out all the stops" to get the BLA in front of regulators.

Even so, the bid for Lucentis' clearance was submitted "ahead of what we hoped for" originally, she said. Genentech had targeted "the mid-point of next year, but everything changed when we saw the first pivotal Phase III data, the MARINA data, in May," Kalmar said.

Anti-VEGF Lucentis (ranibizumab) yielded improved vision in two pivotal Phase III trials, which had never been done before, and even beat Visudyne (verteporfin), the photodynamic therapy from QLT Inc., of Vancouver, British Columbia, in a comparison trial.

Others have tried to show benefit over Visudyne, including New York-based partners Eyetech Pharmaceuticals Inc. and Pfizer Inc. with the FDA-approved Macugen (pegaptanib sodium), whose failure to get trial data that topped results with Visudyne did not prevent OSI Pharmaceuticals Inc., of Melville, N.Y., from buying out Eyetech in a widely scrutinized, $935 million cash-and-stock deal. Macugen and Visudyne have not been compared in a head-to-head trial. (See BioWorld Today, Nov. 24, 2003, and Nov. 15, 2005.)

Separately, Pfizer has made another play in the AMD space, agreeing about a year ago to buy Angiosyn Inc., of La Jolla, Calif., in a deal valued at up to $527 million. Although Angiosyn was working on an AMD compound, parties involved in the buyout deal said Pfizer intends for that drug to be used as a complement, rather than a competitor, to Macugen. (See BioWorld Today, Jan. 25, 2005.)

QLT, feeling the heat from Genentech, said in December that it was reducing its work force by up to 46 percent and trimming sales guidance for Visudyne from a range of between $500 million and $530 million to a range of $480 million to $485 million - and Lucentis isn't even approved yet. The lowered estimate came as a result of more retinal specialists trying Genentech's VEGF inhibitor for colorectal cancer Avastin (bevacizumab) for wet AMD. (See BioWorld Today, Dec. 9, 2005.)

The Lucentis BLA is based on one-year clinical data on efficacy and safety from the two pivotal Phase III trials, ANCHOR and MARINA, as well as one-year clinical data from the Phase I/II FOCUS study.

FOCUS combined Lucentis with Visudyne, and "we saw good efficacy," Kalmar said, with about 90 percent of patients maintaining or improving their vision. But in the two pivotal studies, the data were even better.

"It's not to say you can't use [the drugs] in combination," she said. "The jury's still out on that."

Genentech also is enrolling patients with wet AMD in a Phase IIIb safety study called SAILOR, and data from the Phase IIIb study known as PIER, which is evaluating a less-frequent dosing regimen, are expected in the first half of 2006.

On all fronts, work against AMD has sped along in recent years, and "a lot of that's due to the discovery and cloning of VEGF," done at Genentech, Kalmar said.

Earlier in December, the company submitted its supplemental biologics license application to the FDA for use of Avastin in patients with second-line metastatic colorectal cancer. Avastin was approved in early 2004 as a first-line therapy in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy, and pulled $325.2 million in U.S. sales during the third quarter, a 78 percent jump over the previous year's period. (See BioWorld Today, Feb. 27, 2004, and Dec. 20, 2005.)