FDA splits proposed indications for Blueprint Medicines’ avapritinib into two separate NDAs

Blueprint Medicines Corporation said in an update on its New Drug Application (NDA) for avapritinib for the treatment of adults with PDGFRA , that the FDA has said it plans to administratively split the proposed indications for avapritinib into two separate NDAs, one for PDGFRA Exon 18 mutant GIST, regardless of prior therapy, and one for fourth-line GIST.

Given the acceleration of the ongoing Phase 3 VOYAGER clinical trial of avapritinib in patients with third- and fourth-line GIST and the anticipated availability of top-line data in the second quarter of 2020, the FDA requested top-line data from the VOYAGER trial, Blueprint said.

Furthermore, the FDA indicated these data would be informative in its review of the proposed fourth-line indication and potential clinical benefit in this population, including its evaluation of response rate and safety for the fourth-line indication. An extension of the review period for the fourth-line GIST NDA will likely be required to enable Blueprint Medicines to provide the top-line VOYAGER data to the FDA, Blueprint said.

Jeff Albers, Chief Executive Officer of Blueprint Medicines said that they have had productive dialogue throughout the development of avapritinib, with the FDA about the potential of avapritinib to address important medical needs in subsets of patients with advanced GIST. Albers said Blueprint plans to continue to work closely with the FDA during its review of the separate NDAs for PDGFRA Exon 18 mutant GIST and fourth-line GIST, and we plan to submit the requested VOYAGER trial data as expeditiously as possible.

Blueprint Medicines has completed patient screening in the VOYAGER trial of avapritinib in patients with third- and fourth-line GIST and expects to complete patient enrollment by the end of November 2019 and report top-line data in the second quarter of 2020, the company said. Furthermore, Blueprint Medicines said it plans to prioritize completion of the VOYAGER trial and delay initiation of its COMPASS-2L trial in second-line GIST. Subject to an initial approval of avapritinib, Blueprint Medicines plans to submit a supplemental NDA to the FDA for avapritinib for third-line GIST in the second half of 2020.

Andy Boral, Chief Medical Officer of Blueprint Medicines. said the company is focusing its strategy and resourcing for the avapritinib clinical development program on three core activities: completing the VOYAGER trial and supporting the FDA’s review of NDAs for PDGFRA Exon 18 mutant GIST and fourth-line GIST, submitting an NDA for advanced systemic mastocytosis in the first quarter of 2020, and submitting an NDA for third-line GIST in the second half of 2020. Boral said the company will remain committed to exploring the potential of avapritinib in patients with second-line GIST and working with the GIST community to advance precision medicine approaches that can transform patient care, both of which may be further enabled by a robust dataset from the VOYAGER trial including nearly 500 patients with third- and fourth-line GIST.