What is Lucentis?

Lucentis is a solution to be injected into the eye. It contains the active substance ranibizumab.

What is Lucentis used for?

Lucentis is indicated for the treatment of the "wet" form of neovascular age-related macular degeneration (AMD). This disease affects the central part of the retina (called the "macula"), in the inner part of the eye, and causes the loss of vision "up close". The macula guarantees the central vision, necessary to distinguish the details and therefore carry out daily operations such as driving, reading and recognizing faces. The "wet" form of AMD is determined by the formation of abnormal blood vessels under the macula, which can bleed or exude fluid. Hence the loss of sight. The medicine can only be obtained with a prescription.

How is Lucentis used?

Lucentis is given as a single injection into the affected eye. In the first three months the injection is given once a month. Afterwards, the doctor checks the patient's vision monthly, giving another injection if the condition worsens. The interval between two doses must not be less than one month. Lucentis should be administered by a qualified ophthalmologist (ophthalmologist) with experience in this type of injections. Before each injection the patient receives a local anesthetic to reduce or prevent pain; the eye, the eyelid and the skin around the eye are disinfected. Furthermore, to prevent infections affecting the eye, antibiotic eye drops are prescribed, to be taken in the three days prior to the injection and in the following three days. The patient will receive the necessary instructions to instill the drops on his own.

How does Lucentis work?

The active substance in Lucentis, ranibizumab, is a small fragment of a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) designed to recognize and bind to a specific structure, called an antigen, found in certain cells of the body.

Ranibizumab was created to inhibit a substance called vascular endothelial growth factor A (VEGF-A). The VEGF-A factor is present at high concentrations in the eyes of AMD patients and is responsible for the growth of blood vessels and serum leakage. These effects aggravate the disease. By blocking this factor, ranibizumab reduces the growth of blood vessels and fluid leaks or bleeding.

What studies have been carried out on Lucentis?

The effects of Lucentis were first tested in experimental models before being studied in humans.

The three main Lucentis studies involved 1 323 patients with the wet AMD form. All patients were over 50 years old and had never previously received AMD treatment. Two doses of Lucentis were studied: 0.3 mg and 0.5 mg. The studies had to last for two years, but only one had ended when the medicine was evaluated.

In two studies out of three Lucentis was compared to a sham injection, a procedure similar to Lucentis injection, but without drug administration and performed without a needle. The syringe

it is pressed against the surface of the eye, without actually actually injecting. Patients are unable to tell if the ophthalmologist has administered Lucentis or used the simulated, ineffective procedure. The third study compared Lucentis with photodynamic therapy with verteporfin (PDT, another type of AMD treatment). The main measure of effectiveness was an improvement in vision in the diseased eye one year after the start of treatment, measured on the basis of the standard vision examination with a remote light board. There was no significant deterioration in vision if the number of letters read on the board increased, remained as it was or decreased not more than 15 letters.

What benefit has Lucentis shown during the studies?

Lucentis was more effective in preventing vision deterioration than control medicines. A percentage between 94% and 96% of patients subjected to monthly

treatment with Lucentis did not show a worsening of eyesight compared to 62% of patients treated with fake injections and 64% of patients treated with PDT with verteporfin. The 0.5 mg dose was more effective than the 0.3 mg dose. The view of patients treated with Lucentis also remained better than the sight of subjects treated with fake injections in a study in which injections were given less frequently (one a month in the first three months, then one every three months).

What is the risk associated with Lucentis?

The most frequent side effects reported with Lucentis (seen in more than 1 patient in 10) are increased intraocular pressure (inside the eye), headache, vitritis (inflammation of the eye), vitreous detachment (detachment from the gelatin retina that fills the inside of the eye), retinal hemorrhage (retinal bleeding), visual disturbances, eye pains, floaters (flying flies), conjunctival haemorrhage (bleeding from the vessels of the front of the eye), eye irritation, sensation of a foreign body in the eye, increased lacrimation, blepartitis (inflammation of the eyelids), dry eyes, ocular hyperemia (redness of the eyes), itchy eyes, arthralgia (pain in the joints) and nasopharyngitis (inflammation of the nose and throat). For the full list of all side effects reported with Lucentis, see the Package Leaflet.

Rarely, endophthalmitis (an infection of the eyeball), severe eye inflammation, retinal lesion and cataract (lens opacity) may be observed after Lucentis treatment. In this case it is necessary to intervene as soon as possible. The symptoms of these diseases and the instructions for the medical procedure to be started in the patients concerned are shown in the package insert. Injections into the eye can also cause a temporary increase in eye pressure. The ophthalmologist will check the eye pressure after the injection and, if necessary, take corrective measures. Lucentis should not be used in people who may be hypersensitive (allergic) to ranibizumab or any of the other ingredients. It must also not be used in patients who may have an infection of the eye or surrounding area or with severe intraocular inflammation (inside the eye).

Why has Lucentis been approved?

The Committee for Medicinal Products for Human Use (CHMP) noted that Lucentis produces undesirable effects, which are however counterbalanced by the convincingly demonstrated benefits of the drug which lasted up to two years of use. The Committee decided that the benefits of Lucentis outweigh the risks in the treatment of neovascular (wet) age-related macular degeneration. Since the efficacy of Lucentis was slightly greater in patients receiving the 0.5 mg dose and the most common side effects were not severe, the Committee recommended that the marketing authorization be granted at this dosage .

What measures are being taken to ensure the safe use of Lucentis?

The company that produces Lucentis will provide information packs for doctors (containing, among other things, information on the necessary measures to be taken to minimize the risk of infection associated with ocular injections) and for patients (to help them prepare for treatment with Lucentis, to recognize serious side effects and to know when to request an urgent visit to the doctor). The company will also closely monitor the side effects and safety of the drug.

More information on Lucentis

On 22 January 2007, the European Commission granted Lucentis a marketing authorization valid throughout the European Union to Novartis Europharm Limited. For the full version of the evaluation (EPAR) of Lucentis click here.

Last update of this summary: 11-2008.