Lucentis® (ranibizumab injection)

Lucentis® (ranibizumab injection) is a vascular endothelial growth factor (VEGF) inhibitor approved by the U.S. Food & Drug Administration (FDA) for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO) and diabetic macular edema (DME), all of which cause vision loss and sometimes blindness. Lucentis has been rigorously studied in multiple retinal diseases in 27 clinical trials involving more than 10,500 patients worldwide.

Wet AMD

• Lucentis (ranibizumab .5mg injection) was approved by the U.S. Food and Drug Administration (FDA) on June 30, 2006 for the treatment of wet AMD.
• Information about less-frequent dosing regimens for patients with wet AMD is included in the product label to inform physicians about dosing regimens for individual patients.
• Based on the Genentech HARBOR study, the label was updated on February 6, 2013 to state that although not as effective, patients may be treated with three monthly doses followed by less-frequent-than-monyhly dosing with regular assessment.
• AMD is a leading cause of vision loss in Americans age 60 and older There are two forms of AMD, wet and dry.¹ Wet AMD affects an estimated 1.6 million U.S. adults over the age of 50.²
• Due to the rapid progression and severe, irreversible loss of central vision associated with wet AMD, early diagnosis and treatment are important for successful management.

Macular Edema Following RVO

• Lucentis (ranibizumab .5mg injection) was approved on June 22, 2010 for the treatment of macular edema following RVO
• RVO affects more than 1 million people in the U.S.³ and is the second-most common cause of vision loss due to retinal vascular disease,⁴ which can develop over a long period of time or occur suddenly.
• An estimated 887,000 people are affected by branch-RVO, with approximately 154,000 new cases diagnosed each year in the U.S.³
• An estimated 265,000 people are affected by central-RVO, with approximately 39,000 new cases diagnosed each year in the U.S.³
• RVO affects working-age adults and the elderly and is most prevalent in people over 50 years old as the incidence increases with age.

Diabetic Macular Edema (DME)

• Lucentis (ranibizumab .3mg injection) was approved in [insert date] for treatment of DME.
• Prior to approval of Lucentis, there were no FDA-approved medicines to treat this debilitating eye condition. Laser surgery is a current standard of care for DME is laser surgery that helps seal the leaky blood vessels to slow the leakage of fluid and reduce the amount of fluid in the retina.⁷,⁸
• DME is a leading cause of vision loss among the working-age population of most developed countries.⁷
• More than 560,000 Americans have DME.⁹
• Approximately 55 percent are unaware that they have the disease.⁹

Mechanism of Action

• Lucentis is a recombinant humanized monoclonal antibody fragment (lacking an Fc region). Lucentis is the first VEGF inhibitor specifically designed for use in the eye to bind to and inhibit VEGF-A, a protein that is believed to play a critical role in the growth of new blood vessels (angiogenesis) and the hyperpermeability (leakiness) of the vessels.
• In wet AMD, the abnormal blood vessels grow under the surface of the retina and leak blood and fluid, causing rapid damage to the macula, the portion of the eye responsible for fine, detailed central vision.
• Macular edema following RVO 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.
• DME occurs when abnormal blood vessels leak blood and fluid into the macula causing swelling (edema), which can lead to blurred vision and even vision loss.

Clinical Trial Information

• Wet AMD

  • Lucentis has been studied in multiple randomized, controlled clinical trials, including two pivotal Phase III studies (MARINA and ANCHOR). 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) at two years.
  • Up to 41 percent of patients treated monthly with Lucentis improved their vision 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.
  • The Phase III HARBOR trial was a randomized, controlled study that assessed the efficacy and safety of Lucentis 0.5 mg administered monthly or less-frequently-than-monthly based on regular assessment in 550 patients with wet AMD
  • HARBOR, Lucentis 0.5 mg monthly and less-frequent dosing demonstrated clinically meaningful visual acuity gains (+10.1 letters with 11.3 injections and +8.2 letters with 7.7 injections, respectively).
  • After three initial monthly doses, patients in the less-frequent dosing arm maintained visual acuity gains through month 12, while patients in the monthly arm gained an average of 1 to 2 additional letters.
  • 34.5% of patients who received Lucentis 0.5 mg gained 15 letters from baseline at month 12 compared to 30.2% who received Lucentis 0.5 mg less-frequent-than-monthly.
  • No new safety signals were identified.
  • The pre-specified non-inferiority comparison between 0.5 mg dosed monthly and 0.5 mg dosed less frequently was not met in the HARBOR trial.
  • Although monthly dosing is more effective, patients assessed regularly may be treated less frequently based on retreatment criteria.
  • Fewer side effects related to injection occurred with less-frequent dosing. Some patients have had increased eye pressure before and within 1 hour of an injection. A patient's eye doctor should check a patient's eye pressure and eye health during the week after the Lucentis injection.
  • Uncommonly, Lucentis patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes.
  • 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 (VA) 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.

• Macular Edema following 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 (intravitreal sham-injection, 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).⁵,⁶ During the six to 12-month observation period, all patients were eligible to receive Lucentis through a less-frequent dosing regimen according to standardized re-treatment criteria.
  • 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.⁵,⁶
  • In both studies, 48 to 61 percent of Lucentis patients experienced at least a 15-letter gain in best-corrected VA.⁵,⁶
  • In each study, 1.5 percent of patients lost at least 15-letters or more with monthly injections of Lucentis.⁵,⁶
  • An analysis of the 12-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.⁵,⁶

• DME

  • Lucentis 0.3 mg has been studied for the treatment of patients with diabetic macular edema (DME) including in two identically-designed, parallel confirmatory Phase III studies known as RISE and RIDE. In both studies, patients were randomized to receive monthly injections of either 0.3 mg Lucentis or 0.5 mg Lucentis or monthly sham injections.
  • In the studies, treatment with Lucentis demonstrated improved clinical outcomes including substantial visual gain for many DME patients. Results showed patients who received 0.3 mg Lucentis experienced significant, early (Day 7) and sustained (24 months) improvements in vision:¹⁰
  • More patients who received Lucentis were able to read at least three additional lines (15 letters) on the eye chart at 24 months: RIDE: 34 percent in the 0.3 mg group versus 12 percent in the control group; RISE: 45 percent, 0.3 mg versus 18 percent, control (primary endpoint)¹⁰
  • Patients who received Lucentis had average vision gains exceeding two lines (10 letters) on the eye chart at 24 months: RIDE: 10.9 letters, 0.3 mg versus 2.3 letters, control; RISE: 12.5 letters, 0.3 mg versus 2.6 letters, control¹⁰
  • Significant gains in average vision were observed 7 days after the first treatment¹⁰
  • Patients who received Lucentis were significantly more likely to maintain their vision (lose < 15 letters on the eye chart) at 24 months: RIDE: 98 percent, 0.3 mg versus 92 percent, control; RISE: 98 percent, 0.3 mg versus 90 percent, control¹⁰
  • The most common eye-related side effects are increased redness in the white of the eye, cataract, and increased eye pressure. The most common non-eye-related side effects are nose and throat infections, anemia, and nausea.

Background Information

• 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 was developed by Genentech and the Novartis Ophthalmics Business Unit 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.
• Genentech develops medicines for serious or life-threatening medical conditions and believes they should be accessible for the patients who need them. The company offers a full range of programs and services to meet the needs of patients and health care professionals. What patients need for access, from benefits investigations through patient assistance options, is available through Genentech Access Solutions. For more information, please visit Genentech-Access.com.

Important Safety Information

Lucentis is a prescription medication given by injection into the eye, and it has side effects. Lucentis is not for everyone. You should not use Lucentis if you have an infection in or around the eye or are allergic to Lucentis or any of its ingredients. 

Some Lucentis patients have serious side effects related to the injection. These include serious infections inside the eye, detached retinas, and cataracts. Other uncommon serious side effects include inflammation inside the eye and increased eye pressure. These side effects can make your vision worse. Some patients have had increased eye pressure before and within 1 hour of an injection. Your eye doctor should check your eye pressure and eye health during the week after your Lucentis injection.

Uncommonly, Lucentis patients have had serious, sometimes fatal, problems related to blood clots, such as heart attacks or strokes.

If your eye becomes red, sensitive to light, or painful, or if you have a change in vision, call or visit your eye doctor right away. 

The most common eye-related side effects are increased redness in the white of the eye, eye pain, small specks in vision, and increased eye pressure. The most common non–eye-related side effects are nose and throat infections, headache, lung/airway infections, and nausea. 

Lucentis is for prescription use only. 

Report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.  Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

For additional safety information, please talk to your doctor and see the Lucentis full prescribing information. 

• References

  ¹ National eye institute "Facts About Age-related Macular Degeneration." Available at: http://www.nei.nih.gov/health/maculardegen/armd_facts.asp. Access date June 7, 2012.

  ² Melniknva, Irena, Wet age-related macular degeneration, Nature Reviews Drug Discovery 4, 711-712, September 2005. Available at: http://www.nature.com/nrd/journal/v4/n9/full/nrd1827.html#B1. Access date June 7, 2012.

  ³ Genentech data on file (Based on population-based studies/the Beaver Dam Eye Study 2000 and 2008 and the United States Census).

  ⁴ Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res. 2008;33:111-131.

  ⁵ Brown D, Campochiaro P, Singh R et al. Ranibizumab for Macular Edema following Central Retinal Vein Occlusion: Six-Month Primary End Point Results of a Phase III Study Ophthalmology doi: 10.1016/j.ophtha.2010.02.022.

  ⁶ Campochiaro P, Heier J, Feiner L et al. Ranibizumab for Macular Edema following Branch Retinal Vein Occlusion: Six-Month Primary End Point Results of a Phase III Study Ophthalmology doi: 10.1016/j.ophtha.2010.02.022.

  ⁷National Eye Institute. "Facts About Diabetic Retinopathy." Available at: http://www.nei.nih.gov/health/diabetic/retinopathy.asp. Access date June 7, 2012.

  ⁸Macular Edema, Diabetic; emedicine from WebMD, Medscape Specialits: Opthalmology/Retina; Updated: Oct 7, 2010. Available at: http://emedicine.medscape.com/article/1224138-overview. Access date June 7, 2012.

  ⁹ Bressler NM, Varma R, Doan Q, et al. Prevalence of Visual Impairment from Diabetic Macular Edema and Relationship to Eye Care from the 2005 - 2008 National Health and Nutrition Examination Survey (NHANES) [abstract]. The Retina Society 45th Annual Scientific Meetings, Washington, DC; October 4-7, 2012 (accepted for presentation).

  ¹⁰ Nguyen QD, Brown DM, Marcus DM, et al.; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 Phase III randomized trials: RISE and RIDE. Ophthalmology 2012;119:789-801.