On 9 November 2023, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product trametinib (Spexotras), intended for the treatment of low- and high-grade glioma (LGG and HGG).
The applicant for this medicinal product is Novartis Europharm Limited.
Spexotras will be available as a powder for oral solution containing 0.05 mg/ml after reconstitution. The active substance of Spexotras is trametinib, a protein kinase inhibitor (ATC code: L01EE01). Trametinib is a reversible, highly selective, allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. MEK proteins are components of the extracellular signal-related kinase (ERK) pathway, which is often activated by mutated forms of BRAF in human cancers and is involved in cancer cell survival. By blocking the catalytic activity of MEKs, trametinib inhibits activation of the ERK signalling pathway.
The benefits of Spexotras, in combination with dabrafenib, are an increased overall response rate (ORR; 46.6% versus 10.8%) and progression-free survival (20.1 versus 7.4 months) compared with carboplatin and vincristine chemotherapy for LGG, and an ORR of 56.1% and duration of response of 22.2 months, as measured in a single-arm trial, for HGG.
The most common side effects of trametinib in combination with dabrafenib were pyrexia, rash, headache, vomiting, fatigue, dry skin, diarrhoea, haemorrhage, nausea, dermatitis acneiform, neutropenia, abdominal pain, and cough.
The full indication is:
Low-grade glioma
- Spexotras in combination with dabrafenib is indicated for the treatment of paediatric patients aged 1 year and older with LGG with a BRAF V600E mutation who require systemic therapy.
High-grade glioma
- Spexotras in combination with dabrafenib is indicated for the treatment of paediatric patients aged 1 year and older with HGG with a BRAF V600E mutation who have received at least one prior radiation and/or chemotherapy treatment.
- Spexotras should be initiated and supervised by a qualified physician experienced in the use of anticancer medicinal products.
Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.
Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion.
This product was designated as an orphan medicine during its development. EMA will now review the information available to date to determine if the orphan designation can be maintained.
