Yondelis

Summary

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/262441/2015

EMEA/H/C/000773

EPAR summary for the public

Yondelis

trabectedin

This is a summary of the European public assessment report (EPAR) for Yondelis. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Yondelis.

What is Yondelis?

Yondelis is a cancer medicine that contains the active substance trabectedin. It is available as a

powder that is made up into a solution for infusion (drip into a vein).

What is Yondelis used for?

Yondelis is used to treat adults with two types of cancer:

• advanced soft-tissue sarcoma, a type of cancer that develops from the soft, supporting tissues of the body. 'Advanced' means that the cancer has started to spread. Yondelis is used when treatment with anthracyclines and ifosfamide (other cancer medicines) have stopped working, or in patients who cannot be given these medicines;

• ovarian cancer (cancer of the ovaries) that has relapsed (come back after previous treatment) and is sensitive to medicines containing platinum. Yondelis is used in combination with pegylated liposomal doxorubicin (PLD, another cancer medicine).

Because the numbers of patients with soft-tissue sarcoma and ovarian cancer are low, the diseases are

considered 'rare', and Yondelis was designated an 'orphan medicine' (a medicine used in rare diseases)

on 30 May 2001 (for soft-tissue sarcoma) and on 17 October 2003 (for ovarian cancer).

The medicine can only be obtained with a prescription.

An agency of the European Union

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How is Yondelis used?

Yondelis must be given under the supervision of a doctor who is experienced in the use of chemotherapy (medicines to treat cancer). It should only be used by qualified oncologists (cancer specialists) or other health professionals who are specialised in giving cytotoxic (cell-killing) medicines.

For soft-tissue sarcoma, the recommended dose of Yondelis is 1.5 mg per square metre of body surface area (calculated using the patient's height and weight), given as a single infusion lasting 24 hours every three weeks. For ovarian cancer, it is given at a dose of 1.1 mg/m² every three weeks as an infusion lasting three hours, immediately after the PLD infusion.

Treatment carries on for as long as the patient shows a benefit. It is recommended that Yondelis be given through a central venous line (a thin tube leading from the skin into the large veins just above the heart). To prevent vomiting and to protect the liver, patients must receive an infusion of corticosteroids such as dexamethasone before treatment. If the patient's blood counts are abnormal, infusion with Yondelis should be delayed, the dose of Yondelis should be reduced or other medicines can be used to treat the blood problems. For more information, see the summary of product characteristics (also part of the EPAR).

How does Yondelis work?

The active substance in Yondelis, trabectedin, is a synthetic version of a substance that was originally extracted from a species of tunicate or 'sea squirt' (a marine animal). Cancer is a disease where cells divide too quickly, usually because the way their genes work is faulty. Trabectedin works by attaching to the DNA, the chemical molecule that makes up genes, and preventing some genes in human cells from increasing their activity. This can prevent the cells from dividing too quickly, slowing down the growth of various types of cancer.

How has Yondelis been studied?

For soft-tissue sarcoma, Yondelis has been studied in one main study involving 266 patients with liposarcoma (a sarcoma originating in fat cells) or leiomyosarcoma (a sarcoma originating in 'smooth' or involuntary muscle cells) that was advanced or metastatic (had spread to other parts of the body). All of the patients had been treated previously with an anthracycline and ifosfamide but this treatment had stopped working. The study compared two different dosing schedules of Yondelis: three times per month, or once every three weeks.

For ovarian cancer, Yondelis in combination with PLD was compared with PLD alone in one main study involving 672 women whose disease had come back or got worse after previous treatment. Around two-thirds of the patients had cancer that was sensitive to platinum-containing medicines.

In both studies, the main measure of effectiveness was how long the patients lived without their disease getting worse.

What benefit has Yondelis shown during the studies?

For soft-tissue sarcoma, Yondelis was more effective when it was given once every three weeks than when it was given with the alternative dosing schedule. Patients receiving it once every three weeks lived for an average of 3.8 months without their disease getting worse, compared with 2.1 months in those receiving Yondelis three times per month.

For ovarian cancer, the combination of Yondelis and PLD was more effective than PLD alone: patients receiving the combination treatment lived for an average of 7.3 months without their disease getting worse, compared with 5.8 months in those receiving PLD alone. The effect of Yondelis was more pronounced in the women whose cancer was sensitive to platinum-containing medicines.

What is the risk associated with Yondelis?

Most patients treated with Yondelis can be expected to have side effects. Around 10% of those patients treated with Yondelis as a single agent and 25% treated with Yondelis in combination therapy can be expected to have serious side effects. The most common side effects of any severity were neutropenia (low levels of neutrophils, a type of white blood cell), nausea (feeling sick), vomiting, increase in liver enzymes, anaemia (low red blood cell counts), tiredness, thrombocytopenia (low blood platelet counts), loss of appetite and diarrhoea. Fatal side effects have occurred in 1.9% and 0.9% of patients treated with Yondelis as a single agent and combination therapy, respectively. For the full list of all side effects reported with Yondelis, see the package leaflet.

Yondelis must not be used in patients who have any serious or uncontrolled infection, in combination with the vaccine for yellow fever, or in breast-feeding women. For the full list of restrictions, see the package leaflet.

Why has Yondelis been approved?

The CHMP concluded that Yondelis's benefits are greater than its risks and recommended that it be given marketing authorisation.

Yondelis was originally authorised under 'exceptional circumstances', because, limited information was available at the time of approval on soft-tissue sarcoma. As the company had supplied the additional information requested, the 'exceptional circumstances' ended on 27 May 2015.

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

A risk management plan has been developed to ensure that Yondelis is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Yondelis, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Yondelis

The European Commission granted a marketing authorisation valid throughout the European Union for Yondelis on 17 September 2007.

The full EPAR for Yondelis 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 Yondelis, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

The summary of the opinion of the Committee for Orphan Medicinal Products for Yondelis can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designation

• ovarian cancer:

• soft-tissue sarcoma.

This summary was last updated in 05-2015.

Yondelis

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