Lucentis® (ranibizumab injection)

Full Prescribing Information

Approval and Usage Lucentis® (ranibizumab injection) is a vascular endothelial growth factor (VEGF) inhibitor approved by the U.S. Food and Drug Administration (FDA) on June 30, 2006, for the treatment of neovascular (wet) age-related macular degeneration (AMD) and for the treatment of macular edema following retinal vein occlusion (RVO) on June 22, 2010. Lucentis (0.5 mg) is administered via injection into the back of the eye, also known as an intravitreal injection.

• AMD is a leading cause of vision loss in people over 60. Due to the rapid progression and severe, irreversible loss of central vision associated with the disease, early diagnosis and treatment are important for the successful management of wet AMD.
• RVO affects more than 1 million people in the United States and is the second-most common cause of vision loss due to retinal vascular disease, which can develop over a long period of time or occur suddenly. It occurs when the normal blood flow through a retinal vein becomes blocked, causing swelling (edema) and hemorrhages in the retina, which may result in vision loss.

Lucentis, administered via injection into the eye (also known as an intravitreal injection), is specifically designed and manufactured for use in the eye. It is formulated using the U.S. Pharmacopoeia (USP) Guidelines to meet the specifications required by the FDA for ophthalmic solutions. It is packaged and sold in sterile, preservative-free, single-use vials.

Lucentis is specifically designed and manufactured for use in the eye. It is formulated using the U.S. Pharmacopoeia (USP) Guidelines to meet the specifications required by the FDA for intravitreal therapies. It is packaged and sold in sterile, single-use vials.

• Serious side effects related to the injection procedure were rare. These included serious eye infection, detached retina, and cataract.
• Other uncommon serious side effects included inflammation inside the eye and increased eye pressure.

Mechanism of Action

• Lucentis is an antibody fragment specifically developed for administration into the eye.
• Lucentis is designed to bind to and inhibit VEGF-A, a protein that is believed to play a critical role in the formation of new blood vessels. In wet AMD, these blood vessels grow under the retina and leak blood and fluid causing rapid damage to the macula, the portion of the eye responsible for fine, detailed central vision. In RVO, angiogenesis and hyperpermeability can lead to macular edema, the swelling and thickening of the macula, which is the portion of the eye responsible for fine, detailed central vision.

Clinical Trial Information
AMD

• Lucentis has been studied in multiple randomized, controlled clinical trials, including two pivotal Phase III studies. It has been formally evaluated in all subtypes of wet AMD. In these pivotal studies:
  • Nearly all (90 percent) patients treated monthly with Lucentis maintained their vision (lost less than 15 letters on the study eye chart) for up to two years.
  • Vision in up to 40 percent of patients treated monthly with Lucentis improved by at least 15 letters (three lines) on the study eye chart at two years.
  • Up to 42 percent of patients treated monthly with Lucentis achieved vision of 20/40 or better at two years.
  • Serious side effects related to the injection procedure were rare and included serious eye infection, detached retina, and cataract.
  • Other uncommon serious side effects included inflammation inside the eye and increased eye pressure.
  • Most common eye-related side effects included red eye, eye pain, small specks in vision, the feeling that something is in the eye, and increased tears.
  • Most common non-eye-related side effects included nose and throat infections, headache, respiratory infection, and urinary tract infection.
• In the Phase IIIb PIER study, patients were treated once a month for three months followed by mandatory quarterly injections of Lucentis for a total of 24 months.
  • Patients treated with Lucentis, on average, demonstrated an initial increase in mean visual acuity compared to baseline after three monthly injections.
  • On average, patients treated with Lucentis using the quarterly dosing regimen returned to baseline visual acuity at one year.
• SAILOR is another Phase IIIb study designed with the following objectives:
  • Evaluate the safety of two doses (0.3 mg and 0.5 mg) of Lucentis administered once a month for three months and thereafter as needed based on retreatment criteria for a total of 12 months (Cohort 1)
  • Provide access to Lucentis (0.5 mg only) for patients during the period prior to approval (Cohort 2)
  • Final results suggested that the 0.5 mg dose of Lucentis was not associated with the higher rate of stroke observed during the interim analysis conducted at six months. A trend towards a higher incidence of stroke was seen in patients receiving the 0.5 mg dose at one year (1.2% for 0.5 mg versus 0.7% for 0.3 mg), though this was not statistically significant (p-value=0.21). Rates of adverse events were generally low and consistent with those seen in the pivotal trials of Lucentis.
  • One-year SAILOR efficacy data suggest that treating patients with Lucentis on an as-needed basis may be less effective than monthly dosing.
  • SAILOR is the largest study ever conducted in patients with wet AMD.
• Patients in the United States who completed the treatment phase of the Genentech-sponsored Lucentis studies FOCUS, MARINA or ANCHOR, were eligible to enroll in the HORIZON extension study, which is also ongoing.

RVO

• Lucentis has been studied for the treatment of patients with macular edema following RVO, including in two prospective, randomized, sham-injection controlled Phase III clinical trials – BRAVO and CRUISE. In both studies, patients were randomized to receive monthly injections of 0.3 mg Lucentis or 0.5 mg Lucentis during the first six months of the study (treatment period), after which they were observed during the final six months of the study (observational period).
  • Both studies showed an early (day seven) and sustained vision improvement during the six-month study in patients with macular edema following BRVO (BRAVO) and macular edema following CRVO (CRUISE) receiving monthly injections of 0.3 mg or 0.5 mg Lucentis compared to sham injections.
  • In both studies, 48 to 61 percent of Lucentis patients experienced at least a 15-letter gain in best-corrected VA.
  • In each study, 1.5 percent of patients lost at least 15-letters or more with monthly injections of Lucentis.
  • An analysis of the six-month data from BRAVO and CRUISE showed a safety profile consistent with previous Lucentis trials in wet AMD, with no new safety events identified to date.

Important Safety Information

• Lucentis® (ranibizumab injection) is a prescription medication given by injection into the eye, and it has side effects. Some Lucentis patients have had detached retinas and serious eye infections.  Lucentis should not be used in patients who have an infection in or around the eye or are allergic to Lucentis or any of its ingredients.
• Although not uncommon, Lucentis patients have had eye- and non-eye related blood clots (heart attacks, strokes and death).
• Some patients have had increases in eye pressure within one hour of an injection.
• Serious side effects also include inflammation inside the eye, and rarely, problems related to the injection procedure, such as developing a cataract. These can make a patient's vision worse.
• The most common side effects to a patient's eye are increased redness in the whites of the eye, eye pain, small specks in vision, and the feeling that something is in the eye. The most common non-eye-related side effects are nose and throat infections, headache, and respiratory (lung) infections.
• If a patient's eye becomes red, sensitive to light, painful, or has a change in vision, they should call or visit their eye doctor right away.
• Please visit www.lucentis.com for the Lucentis full prescribing information, and additional important safety information.

Background Information

• Lucentis was discovered by Genentech and is being developed by Genentech and Novartis for diseases or disorders of the eye. Genentech (a member of the Roche Group) retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world.
• The vast majority of patients who receive treatment with Genentech medicines have insurance that covers the cost of their treatment. Genentech is committed to assisting patients whose financial circumstances may prevent them from accessing its medicines. Genentech supports several programs for eligible patients treated for indications approved by the FDA in the United States who do not have insurance or who need assistance with insurance reimbursement. Genentech also makes donations to independent charities that provide co-pay assistance to eligible patients. For more information about treatment and access to Lucentis, call (866) 4 ACCESS or visit GenentechAccessSolutions.com.