dm+d

Unassigned

New Medicines

TuralioTenosynovial giant cell tumour

Information

Turalio
New molecular entity
Not Known
Plexxikon

Development and Regulatory status

Discontinued
Discontinued
Launched
Yes
Mar 21Company has no plans to launch this product in the UK or EU; development discontinued [19].
Jun 20Not recommended for EU approval by CHMP (Negative opinion). CHMP considered 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 may ask for re-examination of the opinion within 15 days of receiving the opinion (but may not present new scientific data at this point) [18].
Aug 19Launched in US. The product is available in the US only through a restricted distribution programme under Risk Evaluation and Mitigation Strategy called the TURALIO REMS Program [17].
Aug 19Approved in US for treatment of adult patients with symptomatic tenosynovial giant cell tumour (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery [16].
May 19The Oncologic Drugs Advisory Committee at FDA has voted in favour of pexidartinib in symptomatic TGCT. There were some concerns about liver toxicity, but a Risk Evaluation and Mitigation Strategy was thought to help prevent harm or identify it sufficiently early [13,14].
Apr 19EMA validates MAA for pexidartinib for treatment of adult patients with symptomatic TGCT, which is associated with severe morbidity or functional limitations, and which is not amenable to improvement with surgery. NDA accepted for priority review by US FDA - a decision is expected by 3/8/19 [12].
Jun 18On the basis of ENLIVEN positive data, Daiichi Sankyo intends to submit an NDA to the US FDA and engage with European regulators for reviewing pexidartinib, for the treatment of tenosynovial giant cell tumour (TGCT)/Pigmented villonodular synovitis [11].
Oct 17Target financial year for launch 2019 [8].
Oct 17ENLIVEN is continuing to completion in order to evaluate its efficacy and safety endpoints. Company announced that top-line results suggest that pexidartinib reduces tumor size in pts with symptomatic tenosynovial giant cell tumor (TGCT) where surgical resection is potentially associated with worsening functional limitation or severe morbidity. Data are expected to be available around March 2018.[7]
Oct 16Daiichi Sankyo and Plexxikon have suspended the PIII ENLIVEN trial on the advice of the Data Monitoring Committee after two recently reported cases of non-fatal, serious liver toxicity. At the time of the suspension, 121 patients had been randomized, just five short of the 126 planned. The DMC also recommended measures to address these safety concerns while maintaining the blinded nature of the study. As a result, ENLIVEN will continue to completion in order to evaluate its efficacy and safety endpoints [6].
Oct 15The FDA has granted Breakthrough Therapy Designation to pexidartinib for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. [5]
Jul 15Approval/launch planned for 2019 [4].
Feb 14Plexxikon was granted an Orphan Drug designation for plexidartinib as a treatment for pigmented villonodular synovitis and giant cell tumour of the tendon sheath [1]

Category

A potent, selective colony colony-stimulating factor 1 receptor (CSF1R) kinase inhibitor [1,3]
PVNS is a rare proliferative neoplastic tumour that affects the synovium and tendon sheaths in young and middle-aged adults of both sexes. Patients are commonly diagnosed in their 20s to 50s. Diffuse PVNS is an aggressive form of the disease, and can affect the entire lubricating membrane of either small or large joints, most commonly the knee. The diffuse form has an average annual incidence of 1.8 cases per million [3]
Tenosynovial giant cell tumour
Oral

Further information

Yes

Trial or other data

Jun 19PIII ENLIVEN RCT (n=174) is published; the authors reported pexidartinib, a CSF1 receptor inhibitor, is first systemic therapy to show robust tumour response in tenosynovial giant cell tumour (overall response in pexidartinib and placebo groups at week 25 = 39% vs 0%; p<0.0001), but hepatotoxicity was an identified risk [15].
Jun 18PIII ENLIVEN data presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO-2018) [11].
Mar 18PIII ENLIVEN study sis due to complete collection of primary outcome data in Dec 18 [10].
Oct 17Daiichi Sankyo announces that the pivotal PIII placebo-controlled ENLIVEN (NCT02371369) study of pexidartinib met its primary endpoint of tumor response as measured by tumor size reduction in patients with symptomatic tenosynovial giant cell tumor (TGCT) where surgical resection is potentially associated with worsening functional limitation or severe morbidity [9].
Jul 15Daiichi Sankyo and Plexxikon’s investigational rare cancer drug PLX3397 has led to prolonged tumour regressions in its PI trial, NCT01004861. The trial results, published in the New England Journal of Medicine, showed that 52% of patients achieved a partial response and 30% had stable disease [2].

Evidence based evaluations