The news just gets better and better for Genentech Inc.'s wet age-related macular degeneration (AMD) drug, Lucentis.

Predicted by Wall Street to snag the largest share of the wet AMD market upon approval, Lucentis (ranibizumab), a vascular endothelial growth factor (VEGF) inhibitor, recently demonstrated improved visual acuity over Visudyne (verteporfin) photodynamic therapy in a head-to-head study in patients with the predominately classic form of wet AMD. Results caused shares of Visudyne's developer, QLT Inc., to fall nearly 11 percent.

Shares of QLT (TSE:QLT) closed at C$7.79 (US$6.57) Tuesday, down C$0.93.

"We're very encouraged by these results," said Dawn Kalmar, spokeswoman for South San Francisco-based Genentech. "Lucentis is, to date, one of the few therapies that has held up through the results in Phase I trials and continues to show positive results in Phase III."

The company plans to file a biologics license application in December and will request a priority six-month review. The BLA would include one-year data from the head-to-head study with Visudyne, as well as the MARINA trial, in which Lucentis showed statistical significance over placebo in patients with minimally classic and occult lesions. In that study, about 95 percent of patients treated with Lucentis maintained or improved vision (defined as a loss of less than 15 letters in visual acuity) at one year, compared to about 62 percent in the placebo arm. (See BioWorld Today, May 25, 2005.)

Preliminary results from the Phase III ANCHOR (Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD) study showed a clinical benefit of Lucentis over Visudyne. One-year data from the trial demonstrated that Lucentis met its primary endpoint of maintaining or improving vision in patients - 94 percent of those treated with 0.3 mg, and 96 percent of those given 0.5 mg - compared to about 64 percent of patients receiving Visudyne.

"This trial really had a higher bar to pass, since it was [tested] against an active control arm," Kalmar said. "So we're pleased that we're seeing similar results."

Lucentis also showed statistical significance in the secondary endpoint, defined as the mean change in visual acuity from baseline to month 12. Patients receiving Lucentis in once-monthly intravitreal injections, on average, recorded an improvement in visual acuity, while patients in the Visudyne arm showed a decline.

While QLT shares were under pressure Tuesday, it wasn't nearly as dramatic as the 45 percent plunge felt in May by New York-based Eyetech Pharmaceuticals Inc., which develops Macugen, an approved VEGF inhibitor for AMD, following results from Genentech's Phase III trial of Lucentis vs. placebo.

While Macugen, which is co-marketed by New York-based Pfizer Inc., would face direct competition from Lucentis, QLT's Visudyne could hold on to a certain share of the market through combination therapy. Third-quarter sales of Visudyne totaled about $124 million, and QLT has estimated annual sales of its photodynamic therapy to fall between $500 million to $530 million.

"We believe combination therapy will be used because of the safety issues," said Tamara Hicks, spokeswoman for Vancouver, British Columbia-based QLT, adding that the use of Visudyne could help limit the frequency for intravitreal injections. We think physicians will go that way, as well," she said. "We have several ongoing studies [evaluating Visudyne in combination with] anti-VEGF drugs and intravitreal steroid injections."

Visudyne already is being studied in combination with Lucentis. In May, Genentech and partner, Basel, Switzerland-based Novartis, reported results from a Phase I/II trial of Lucentis in combination with Visudyne, showing that about 90 percent of patients receiving both treatments had maintained or improved vision compared to 68 percent who received Visudyne alone.

In addition to the MARINA and ANCHOR studies, Genentech has two other Lucentis trials ongoing. The first is a Phase IIIb study evaluating a less frequent dosing schedule. Patients are administered the drug once a month for three months, and then once every three months for the remainder of a two-year period.

"That's in response to a lot of the physicians out there, who are questioning whether Lucentis can be dosed less frequently so patients don't have to come in every single month," Kalmar told BioWorld Today. Depending on the results from that study, the company could file a supplemental BLA.

Genentech also initiated enrollment in a 5,000-patient safety study that will be testing Lucentis in both treatment-na ve and treatment-experienced patients. All earlier Lucentis studies involved treatment-na ve subjects only.

The company has not yet announced marketing and sales projections for the drug. The National Eye Institute has reported that there are about 1.7 million cases of AMD in the U.S., and about 20 percent of those include the more severe wet form of the disease. The numbers are expected to grow to almost 3 million by 2020.

With the positive AMD results, Genentech also might consider testing Lucentis in other VEGF-mediated eye diseases, such as diabetic macular edema and diabetic retinopathy, Kalmar said.

Though there has been talk of the company's cancer drug, Avastin, used to treat AMD, Kalmar said Genentech has concerns about the potential systemic safety effects of Avastin.

"That's why, back in the 1990s, we developed Lucentis," she said. "Anti-VEGF therapies do come with side effects" but Lucentis provides a "localized treatment for a local disease" and has a half-life of only four hours, compared to 21 days for Avastin.

Shares of Genentech (NYSE:DNA) closed at $93.90 Tuesday, up 79 cents.