Lucentis Effective Against Macular Degeneration

October 10, 2006

Two studies show that Lucentis (ranibizumab) may offer effective treatment against neovascular age-related macular degeneration.

The first study showed that patients receiving Lucentis injections over about two years improved their vision by more than one line on a standard eye-chart. Participants receiving sham injections lost over two lines.

The second study showed that, at one year, patients receiving Lucentis injections on average gained two lines of visual acuity pm an eye-chart. In contrast, patients receiving photodynamic therapy (as sham treatment) lost about two lines. Bacterial infections inside the eye occurred in one of every 2,000 injections.

The studies appeared in the October 5 issue of the New England Journal of Medicine (NEJM) and were reported by MedPage Today on October 4.

Clinical Trials

The trial by Philip Rosenfeld, MD, PhD, of the Bascom Palmer Eye Institute showed that two years of Lucentis treatment improved mean visual acuity in people with choroidal neovascularization related to macular degeneration, and prevented loss of vision. Adverse event rates were low.

The trial – called the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA) – included 716 participants randomized to receive either Lucentis (24-monthly injections, 0.3 mg or 0.5 mg) or placebo injections.

At one year, 94.5% of participants receiving Lucentis (0.3 mg) and 94.6% of those receiving Lucentis (0.5 mg) lost <15 letters of vision, versus 62.2% of participants receiving placebo injections. Improvements in visual acuity of ≥ 15 letters were 24.8% in the Lucentis (0.3 mg), 33.8% in the Lucentis (0.5 mg) group, and 5.0% in the placebo-injection group.

Also at one year, ~40% of participants receiving Lucentis had at least 20/40, versus 11.3% in the placebo-injection group.

At two years, participants receiving Lucentis had superior vision, compared with placebo: 34.5% 42.1% in the 0.3 mg and 0.5 mg groups, respectively, had at least 20/40 vision, versus 5.9% among those receiving placebo injections.

The adverse event rate was low, and the researchers noted that the trial was not designed to detect small differences in uncommon adverse-event rates. They concluded that Lucentis showed high effectiveness with a low rate of adverse events.

Results from a second, similar study – Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) – in the same issue of the NEJM presented one-year results of the two-year study.

Results from this study of 423 participants showed that Lucentis (0.3 mg or 0.5 mg) prevented loss of central vision and improved visual acuity at one year, compared with photodynamic therapy using Visudyne (verteporfin), and had a low adverse-event rate. Moreover, the study’s results suggested a dose-response effect, according to authors David Brown, MD, of Vitreoretinal Consultants at Methodist Hospital in Houston, and colleagues.

Dr Brown and colleagues commented that the first-year results of ANCHOR and the two-year results of MARINA, when taken together, show Lucentis to be "effective with an acceptable adverse-event profile in the treatment of all angiographic subtypes of choroidal neovascularization associated with age-related macular degeneration."

Lucentis vs. Avastin

In an editorial in the same issue, Edwin Stone, MD, of the Carver Center for Macular Degeneration at the University of Iowa, notes that age-related macular degeneration has become and epidemic in the developed world.

Dr Stone estimates that, in about 10% of people affected by age-related macular degeneration, a choroidal neovascular complication develops – a phenomenon that “is responsible for the vast majority of cases of legal blindness attributable to this disease”. Researchers have sought an effective treatment for choroidal neovascularization for over two decades.

Although he calls the effectiveness of ranibizumab “miraculous”, Dr Stone proposes that ranibizumab should be compared in clinical trials with Avastin (bevacizumab) in treating choroidal neovascularization.

Lucentis and Avastin are both monoclonal antibodies that inhibit vascular endothelial growth factor (VEGF). They differ only in molecular weight. Both are marketed by Genentech.

Dr Stone speculates that bevacizumab’s relatively higher molecular weight may influence its effectiveness:

“The primary molecular difference between these two drugs is their molecular weight: ranibizumab is a 48-kD Fab fragment, whereas bevacizumab is a complete 149-kD antibody. The difference in molecular weight could result in differing abilities of the drugs to reach their site of action (smaller may be better) and to stay in the eye after injection (larger may be better).”

Dr Stone also points out that bevacizumab has been shown in small studies to be effective in treating choroidal neovascularization – and its price is less than 1/10 of ranibizumab’s (>$2,000 per ranibizumab dose, versus <$150 per bevacizumab dose):

“Bevacizumab was approved by the Food and Drug Administration (FDA) as a treatment for metastatic colon cancer in 2004, and ranibizumab was FDA-approved for treatment of choroidal neovascularization this past June. Before the approval and release of ranibizumab, some physicians used bevacizumab in an off-label manner as a treatment for choroidal neovascularization.

“Three uncontrolled, retrospective studies with limited follow-up and one small, prospective study of such off-label use suggested that bevacizumab was reasonably safe and fairly effective for the treatment of choroidal neovascularization. Some physicians still use this drug because its cost is dramatically lower than that of ranibizumab.”

He also noted that a “head-to-head study of ranibizumab and bevacizumab and a careful evaluation of an ‘induction and follow-up’ strategy with either drug are probably the next most useful steps in this field.”

Lucentis "is an absolutely spectacular drug compared with treatments we had in the past,” Dr Stoen reportedly said. “But what if it turns out that the $150 stuff is just as good?"

Sources:
Lucentis Stalls Blood Vessel Growth in Macular Degeneration (CME/CE), MedPage Today, October 4, 2006.
Ranibizumab for neovascular age-related macular degeneration. Rosenfeld PJ et al, New England Journal of Medicine, volume 355, pages 1419-1431, 2006.
A very effective treatment for neovascular macular degeneration. Stone EM, New England Journal of Medicine, volume 355, pages 1493-1494, 2006.
Ranibizumab versus verteporfin for neovascular age-related macular degeneration. Brown DM et al, New England Journal of Medicine, volume 355, pages 1432-1444, 2006.

Posted: October 2006


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