Genentech, Inc. announced that a phase IIIb clinical study of a quarterly dosing regimen of the investigational drug Lucentis (ranibizumab) for the treatment of wet age-related macular degeneration (AMD) met its primary efficacy endpoint by preventing vision loss as measured by mean change in visual acuity from baseline to month 12.
In this study, called PIER, patients receive Lucentis (0.3 mg or 0.5 mg respectively) or sham injections once per month for the first three months followed thereafter by doses once every three months for a total of 24 months. One-year data from this study were presented at the Retinal Physician Symposium in the Bahamas. The pivotal phase III studies of Lucentis (MARINA and ANCHOR) evaluate a monthly treatment schedule.
In the PIER study, patients treated with Lucentis, on average, demonstrated an initial increase in mean visual acuity compared to baseline after three monthly injections. At month three, patients treated with Lucentis, on average, gained 2.9 letters and 4.3 letters (0.3 mg and 0.5 mg dose groups, respectively) compared to a loss of 8.7 letters among patients in the sham group. After the first three monthly injections, patients treated with Lucentis received additional doses at months five, eight and 11. On average, patients treated with Lucentis returned to baseline visual acuity by month 12, while patients in the sham group experienced significant vision loss. At month 12, patients treated with Lucentis lost 1.6 letters and 0.2 letters (0.3 mg and 0.5 mg) compared to a loss of 16.3 letters in the sham group, on average [p less than or equal to 0.0001].
"The results of the Lucentis pivotal studies have changed the expectations for the treatment of wet AMD," said Hal Barron, M.D., Genentech senior vice president, Development and chief medical officer. "While the PIER regimen provided a 16-letter benefit compared to sham, the data suggest that treating patients on a quarterly basis may be less effective than monthly or individualized dosing. Data from ongoing phase IIIb studies and emerging results from our Investigator Sponsored Trials should help us learn more about the optimal dosing regimen for patients."
Consistent with earlier trials of Lucentis, common side effects that occurred more frequently in the Lucentis groups than in the control group at one year were mild to moderate and included conjunctival haemorrhage, eye pain and increased intraocular pressure. There were no reported cases of endophthalmitis, serious intraocular inflammation or other key ocular serious adverse events. There were no deaths, myocardial infarctions or cerebral vascular events in the first year of the study.
The one-year data from this study were submitted to the US Food and Drug Administration (FDA) for consideration as the FDA reviews the Biologics License Application (BLA).
Among patients treated with Lucentis, 83 per cent (0.3 mg) and 90 per cent (0.5 mg) lost fewer than 15 letters in visual acuity compared to baseline, a secondary endpoint of the study, compared with 49 percent in the control group.
12 per cent (0.3 mg) and 13 per cent (0.5 mg) of those treated with Lucentis improved vision by a gain of 15 letters or more, a secondary endpoint of the study, compared with approximately 10 per cent of those in the control group.
30 per cent (0.3 mg) and 28 per cent (0.5 mg) of those treated with Lucentis achieved 20/40 vision at 12 months, an exploratory endpoint of the study, compared to 11 per cent in the sham group.
Genentech submitted a BLA to the FDA for Lucentis on December 29, 2005 and was granted a Priority (six-month) Review. The FDA has until the end of June 2006 to take action on the filing. The submission was based on one-year clinical efficacy and safety data from two pivotal Phase III trials, MARINA and ANCHOR, as well as one-year clinical data from the Phase I/II FOCUS trial. Two-year data from the MARINA study and one-year data from the PIER study were submitted to the FDA after the initial BLA submission. Data from these studies demonstrate that Lucentis is the first investigational therapy to have improved vision in patients with wet AMD in two pivotal Phase III clinical trials. In addition, Lucentis is the first investigational therapy to have demonstrated a clinical benefit compared to verteporfin (Visudyne) photodynamic therapy (PDT) in a head-to-head clinical study (ANCHOR).
PIER (A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovasularization with or without Classic CNV Secondary to Age-Related Macular Degeneration) is a study of 184 patients in the United States with predominantly classic, minimally classic or occult with no-classic wet AMD. In this study, patients were randomized 1:1:1 to receive Lucentis (0.3 mg or 0.5 mg) or sham injections once a month for the first three months followed thereafter by doses once every three months for a total of 24 months. Exclusion criteria included prior subfoveal laser treatment, PDT or experimental treatments for wet AMD. Visual acuity was measured using the Early Treatment of Diabetic Retinopathy (ETDRS) chart, the standard method of quantifying visual acuity.
Lucentis (ranibizumab) is a humanized therapeutic antibody fragment developed at Genentech and designed to bind and inhibit VEGF-A, a protein that is believed to play a critical role in angiogenesis (the formation of new blood vessels). Lucentis is designed to block new blood vessel growth and leakiness, which lead to wet AMD disease progression and vision loss. Lucentis is being developed by Genentech and the Novartis Ophthalmics Business Unit for diseases or disorders of the eye. Genentech retains commercial rights in the United States and Canada, and Novartis has exclusive commercial rights for the rest of the world.