NEW YORK – The European Commission has granted conditional marketing authorization to Blueprint Medicines' avapritinib (Ayvakyt) for the treatment of unresectable or metastatic gastrointestinal stromal tumors with a PDGFRA D842V mutation.
The EC based its decision on the results of the Phase I NAVIGATOR trial, in which the overall response rate in 38 patients was 95 percent on avapritinib, with 13 percent experiencing a complete response. Median progression-free survival was 24 months and overall survival was not reached.
Approximately 6 percent of GIST patients have PDGFRA exon 18 mutations, of which the D842V mutation is the most common. The US Food and Drug Administration earlier this year approved avapritinib for advanced GIST patients with PDGFRA exon 18 mutations, apparently comprising a broader GIST population than addressed by the EC approval.
At least one retrospective study has shown that the subset of patients with PDGFRA D842V-mutated GIST don't respond to imatinib (Novartis' Gleevec) in the first-line setting. The European Society for Medical Oncology recommends that all GIST patients should be evaluated for molecular alterations.
"As we progress toward our [avapritinib] launches in Europe, we are focused on raising awareness about the therapy's differentiated clinical profile and the importance of mutational testing, and working closely with health authorities to enable patient access to [the drug] as rapidly as possible," Blueprint CEO Jeff Albers said in a statement.
In announcing the EC approval, Blueprint said that it will first launch the drug in Germany, though the timing of avapritinib's availability in other countries may depend on local reimbursement and access pathways. As part of the conditional marketing authorization, Blueprint will conduct an observational study in avapritinib-treated patients with PDGFRA D842V mutant GIST.