The European Medicines Agency (EMA) has recommended the refusal of the marketing authorisation for pexidartinib (Turalio), a medicine intended for the treatment of tenosynovial giant cell tumour.
The Agency issued its opinion on 25 June 2020. The company that applied for authorisation, Daiichi Sankyo Europe GmbH, may ask for re-examination of the opinion within 15 days of receiving the opinion.
Turalio was developed as a medicine for treating adults with tenosynovial giant cell tumour that can cause pain and markedly reduce physical function. It was for use when other treatments, including surgery, could no longer be used or were unsuitable. Tenosynovial giant cell tumour is a noncancerous condition in which the tissue surrounding the inner joint surfaces and tendons, called the synovial lining or synovium, expands abnormally and forms growths in and around the joint.
Turalio contains the active substance pexidartinib and was to be available as capsules.
Turalio was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 19 March 2015 for the treatment of tenosynovial giant cell tumour, localised and diffuse type.
The active substance in Turalio, pexidartinib, works by blocking a receptor called CSF1R to which a protein called CSF-1 attaches. CSF-1 is produced in large amounts by tenosynovial giant cell tumours, and it causes immune cells called macrophages to build up in the joints and cause the outgrowths. By blocking CSF1R, the medicine reduces the activity of CSF-1, which was expected to prevent tumour growth and help to reduce symptoms of the disease.
To support its application, the company presented results from a main study involving 120 adults with advanced tenosynovial giant cell tumour that could not be treated in other ways. It looked at the change in tumour size after patients received either Turalio or placebo for 25 weeks.
The Agency was concerned that although the main study found that tumours shrank in patients treated with Turalio, there was only a small improvement in symptoms such as pain and the ability to use the joint. It was not clear how long this effect lasts. There was also serious concern about unpredictable, potentially life-threatening effects of Turalio on the liver. Therefore, the Agency’s opinion was that the benefits of Turalio did not outweigh its risks and it recommended refusing marketing authorisation.
The company informed the Agency that there are no consequences for patients in clinical trials or in compassionate use programmes with Turalio.