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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/277668/2016

EMEA/H/C/003985

EPAR summary for the public

Opdivo

nivolumab

This is a summary of the European public assessment report (EPAR) for Opdivo. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Opdivo.

For practical information about using Opdivo, patients should read the package leaflet or contact their doctor or pharmacist.

What is Opdivo and what is it used for?

Opdivo is a cancer medicine used to treat adults with:

•    advanced melanoma, a type of skin cancer that has spread to other parts of the body or cannot be surgically removed. For this purpose, Opdivo is used on its own or together with a medicine called ipilimumab;

•    a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread locally or to other parts of the body in patients who have previously been treated with other cancer medicines (chemotherapy);

•    advanced renal cell carcinoma, a type of kidney cancer that has spread throughout the body and cannot be surgically removed. It is only used in patients who have been previously treated with other cancer medicines. For this use, Opdivo is used on its own.

Opdivo contains the active substance nivolumab.

How is Opdivo used?

Treatment with Opdivo must be started and supervised by a doctor experienced in the use of cancer

medicines. The medicine can only be obtained with a prescription.

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Opdivo is available as a concentrate that is made up into a solution for infusion (drip) into a vein. The dose and frequency to be given depends on whether it is used alone or in combination with ipilimumab. Treatment is given for as long as the patient benefits from it. The doctor may need to delay doses if certain side effects occur, or stop treatment altogether if side effects are severe. For further information, see the package leaflet.

How does Opdivo work?

The active substance in Opdivo, nivolumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found in certain cells in the body.

Nivolumab has been designed to attach to a receptor called PD-1 which is found on certain cells of the immune system called T cells. Cancer cells can produce proteins (PD-L1 and PD-L2) that attach to this receptor and switch off the activity of the T cells, preventing them from attacking the cancer. By attaching to the receptor, nivolumab prevents PD-L1 and PD-L2 from the cancer cells from switching off the T cells, thereby increasing the ability of the immune system to kill cancer cells.

What benefits of Opdivo have been shown in studies?

Opdivo has been shown to be effective in treating patients with advanced melanoma, NSCLC and advanced renal cell carcinoma:

•    In melanoma, Opdivo used on its own was studied in two main studies in patients with advanced disease. The first study involving 418 previously untreated advanced melanoma patients found that patients treated with Opdivo survived longer than patients who received the cancer medicine dacarbazine: 73% of patients treated with Opdivo were alive at 12 months compared with 42% of patients given dacarbazine. The second study looked at 405 advanced melanoma patients whose disease had got worse despite previous treatment with a cancer medicine. In this study, where patients were followed up for at least 6 months, around 32% (38 out of 120) of patients given Opdivo responded to treatment and had a reduction in their tumours compared with about 11% (5 out of 47) of patients given investigator's choice of treatment (dacarbazine or a combination of carboplatin and paclitaxel).

An additional study in 945 previously untreated advanced melanoma patients investigated Opdivo in combination with ipilimumab, Opdivo used alone or ipilimumab used alone. Patients who were given Opdivo plus ipilimumab lived for another 11.5 months without their disease getting worse and patients given only Opdivo lived for another 6.9 months without their disease getting worse. Patients given only ipilimumab lived for only 2.9 months without their disease getting worse. The study included patients whose cancer cells produced high levels of PD-L1 as well as patients whose cancer cells produced low levels of PD-L1. Improvements in the time patients lived without their disease getting worse when treated with Opdivo plus ipilimumab relative to Opdivo used on its own were only seen for patients whose cancer cells produced low levels of PD-L1.

•    In NSCLC that had spread locally or to other parts of the body, Opdivo has been shown to improve the average time patients survived compared with docetaxel (another cancer medicine). Studies have shown benefit in two forms of NSCLC, known as non-squamous and squamous.

For non-squamous NSCLC, one main study involved 582 patients whose disease had progressed despite previous treatments. The average survival with Opdivo was around 12.2 months, compared with 9.4 months with docetaxel. For squamous NSCLC, a study involving 272 patients showed that patients given Opdivo survived for around 9.2 months, compared with 6.0 months in patients given docetaxel. Supportive information was also provided from another study indicating that Opdivo

could produce a response in patients with squamous NSCLC whose disease had progressed despite several previous treatments.

• In advanced renal cell carcinoma, Opdivo was compared with everolimus in one main study

involving 821 patients whose disease advanced despite previous treatment. Patients given Opdivo survived for around 25.0 months, compared with 19.6 months in patients given everolimus.

What are the risks associated with Opdivo?

The most common side effects with Opdivo (which may affect more than 1 in 10 people) are tiredness, diarrhoea, nausea (feeling sick), rash and pruritus (itching), and decreased appetite, most of which are mild to moderate in severity. These side effects were also the most common side effects when Opdivo was used together with ipilimumab. In addition, hypothyroidism (an underactive thyroid gland), vomiting, colitis (inflammation of the gut), abdominal pain, arthralgia (joint pain) and headache were seen.

Opdivo is also commonly associated with side effects related to the activity of the immune system on body organs. Most will resolve following appropriate treatment or on stopping Opdivo.

For the full list of all side effects and restrictions with Opdivo, see the package leaflet.

Why is Opdivo approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Opdivo's benefits are greater than its risks and recommended that it be approved for use in the EU.

The CHMP considered that Opdivo has been convincingly shown to benefit patients with certain advanced cancers (melanoma, NSCLC or renal cell carcinoma) by either increasing patients' survival or the time they could live without their disease getting worse. Side effects were considered manageable with appropriate measures and were outweighed by the benefits.

What measures are being taken to ensure the safe and effective use of Opdivo?

The company that makes Opdivo will provide educational packs for doctors who are expected to prescribe Opdivo containing information on how the medicine should be used and how to manage side effects, particularly side effects related to the activity of the immune system. The company will also provide an alert card for patients with information on the risks of the medicine, as well as instructions on when to contact their doctor if they experience symptoms. The company will also provide further data on the long-term benefits of Opdivo and carry out analyses to try to identify which patients are most likely to benefit from treatment with the medicine.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Opdivo have also been included in the summary of product characteristics and the package leaflet.

Other information about Opdivo

The European Commission granted a marketing authorisation valid throughout the European Union for Opdivo on 19 June 2015.

The full EPAR and risk management plan summary for Opdivo can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more

information about treatment with Opdivo, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 05-2016.

Opdivo

EMA/277668/2016

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