Blueprint Medicines Corporation , a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT™ (avapritinib) for the treatment of adult patients with advanced systemic mastocytosis (SM). AYVAKIT is a potent and selective inhibitor of D816V mutant KIT, the primary driver of SM, and is being developed to treat advanced and non-advanced forms of the disease.
Blueprint Medicines requested priority review for this application, which, if granted, could result in a six-month review process. The FDA has a 60-day filing review period to determine whether the sNDA is complete and acceptable for filing. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematological neoplasm and mast cell leukemia.
"Today's submission is an important step toward our goal of bringing AYVAKIT to patients with advanced systemic mastocytosis, a debilitating and life-threatening rare disease," said Fouad Namouni, M.D., President, Research & Development. "Our application is based on an unprecedented clinical dataset in this disease, which showed that patients receiving AYVAKIT had high overall response and complete remission rates, with prolonged survival, and the treatment was generally well-tolerated. We look forward to working closely with the FDA during the review, as we seek to introduce the first precision therapy targeting the underlying cause of systemic mastocytosis."
SM is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including aggressive SM, SM with an associated hematological neoplasm and mast cell leukemia. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor overall survival.
Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often persist across all forms of SM despite treatment with a number of symptomatic therapies. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, or isolate themselves to protect against unpredictable triggers. Currently, there are no approved therapies for the treatment of SM that selectively inhibit D816V mutant KIT.
AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. This medicine is approved in Europe under the brand name AYVAKYT for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation.
AYVAKIT/AYVAKYT is not approved for the treatment of any other indication, including SM, in the U.S. by the FDA or in Europe by the European Commission, or for any indication in any other jurisdiction by any other health authority.
Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and indolent SM.
Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of AYVAKIT in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.