On July 18, 2019 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that the European Medicines Agency (EMA) has validated the company’s Marketing Authorization Application (MAA) for avapritinib for the treatment of adult patients with PDGFRα D842V mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, and fourth-line GIST (Press release, Blueprint Medicines, JUL 18, 2019, View Source [SID1234537608]). Validation of the MAA confirms that the application is sufficiently complete to begin the formal review process. Avapritinib is an investigational, potent and highly selective KIT and PDGFRA inhibitor for patients with advanced GIST. The European Commission has granted orphan medicinal product designation to avapritinib for the treatment of GIST.

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"Prognoses are traditionally poor for patients with PDGFRα D842V mutant GIST and fourth-line GIST, and currently no effective therapy exists for either population," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "Avapritinib is specifically designed to inhibit the disease drivers of GIST, including mutant kinases associated with treatment resistance, representing a promising therapeutic approach. We look forward to working expeditiously with the EMA to bring this potential new treatment option to patients."

In June 2019, Blueprint Medicines announced the submission of a New Drug Application to the U.S. Food and Drug Administration (FDA) for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant GIST, regardless of prior therapy, and fourth-line GIST.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. Because currently available therapies primarily bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Mutational testing is critical to tailor therapy to the underlying disease driver and is recommended in expert guidelines. Currently, there are no approved therapies for patients with KIT-driven GIST whose disease progresses beyond imatinib, sunitinib and regorafenib. In patients with metastatic PDGFRα D842V-driven GIST, progression occurs in a median of approximately three to four months with available therapy.

About Avapritinib

Avapritinib is an investigational, oral precision therapy that selectively and potently inhibits KIT and PDGFRA mutant kinases. It is a type 1 inhibitor designed to target the active kinase conformation; all oncogenic kinases signal via this conformation. Avapritinib has demonstrated broad inhibition of KIT and PDGFRA mutations associated with GIST, including potent activity against activation loop mutations that are associated with resistance to currently approved therapies.

Blueprint Medicines is initially developing avapritinib for the treatment of advanced GIST, advanced systemic mastocytosis (SM), and indolent and smoldering SM. The FDA has granted Breakthrough Therapy Designation to avapritinib for two indications: one for the treatment of unresectable or metastatic GIST harboring the PDGFRα D842V mutation and one for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia. The European Commission has granted orphan medicinal product designation to avapritinib for the treatment of GIST and mastocytosis.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.