EMA Recommends Granting a Conditional Marketing Authorisation for Larotrectinib

First ‘histology-independent’ treatment in the EU for solid tumours with a NTRK gene fusion

On 26 July 2019, the European Medicines Agency (EMA) published the highlights from July 2019 meeting of its Committee for Medicinal Products for Human Use (CHMP). The EMA announced that the CHMP recommended granting a conditional marketing authorisation for larotrectinib (Vitrakvi), the first ‘histology-independent’ treatment in the European Union (EU) for solid tumours with a neurotrophic tyrosine receptor kinase (NTRK) gene fusion.

NTRK gene fusions occur very frequently in a number of rare cancers.

Vitrakvi is recommended for the treatment of adult and paediatric patients with solid tumours that display the NTRK gene fusion. Treatment with Vitrakvi is recommended for patients with metastatic disease or whose tumour cannot be surgically removed, and who have no other satisfactory treatment options. 

Vitrakvi is the first so-called ‘histology-independent’ cancer treatment recommended for approval in the EU. This means that it can be used to treat solid tumours with this specific gene aberration, regardless of where in the body the primary tumour originated. Before patients can be started on the medicine, the presence of the NTRK gene fusion in the tumour should be confirmed by a validated test.

The active substance in Vitrakvi, larotrectinib, targets a very specific genomic alteration of a patient’s tumour. This occurs when NTRK genes that encode specific proteins are abnormally fused to a gene. This aberration, called NTRK gene fusion, leads to the development of proteins that can cause cancer cells to grow. Vitrakvi blocks the action of these proteins and in doing so inhibits the growth of the cancer. 

NTRK gene fusions can be observed very frequently in a certain number of rare cancer types that affect both adults and children. In addition, this gene fusion occurs rarely in some of the most common cancer types. 

The efficacy and safety of Vitrakvi were studied in three single-arm trials (i.e. studies with no control group) that included a total of 102 adults and children with cancer that were evaluated. These patients had either already received standard therapy, or would have had to undergo disfiguring surgery, or were unlikely to respond to available therapies.

In total, 67% patients responded to treatment with Vitrakvi. Of those, the response lasted six months or longer in 88% and 12 months or longer in 75%. Tumour responses were seen both in rare tumour types such as infantile fibrosarcoma and salivary gland tumours, as well as in common diseases such as lung and colon cancers.

The most common side effects were tiredness, increased levels of liver enzymes, dizziness, constipation, nausea, anaemia, and vomiting.

The CHMP recommended a conditional approval for this medicine. This is one of the EU's regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, in cases where the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.

The opinion adopted by the CHMP is an intermediary step on Vitrakvi’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once the marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each EU Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.