Benzinga | Dec 7, 2020 08:09AM EST

Blueprint Medicines Highlights Data Presented At 62nd ASH Annual Meeting

CAMBRIDGE, Mass., Dec. 7, 2020 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ:BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced data from six oral and poster presentations highlighted at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. These data demonstrate the company's broad efforts to understand the disease burden, accelerate the diagnosis and transform the treatment of systemic mastocytosis (SM).

"The medical needs in systemic mastocytosis are significant and urgent, and our presentations at the ASH annual meeting demonstrate our efforts to help address these challenges in collaboration with disease experts and the patient community," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT, an investigational precision therapy for the treatment of SM, is the only potent KIT D816V inhibitor to show a high complete remission rate in advanced SM, as well as improvements in mast cell burden, disease symptoms and quality of life in non-advanced SM. With this foundation of unprecedented clinical data, we continue to build momentum toward bringing AYVAKIT to patients. Later this month, we plan to submit a supplemental new drug application to the FDA for AYVAKIT for advanced SM, and we continue to globally enroll the registrational PIONEER trial for non-advanced SM."

Pure Pathologic Response (PPR) Measures Reduction and Elimination of Mast Cell Burden in Advanced SM, and Significantly Correlates with Improved Overall Survival (OS)

The IWG-MRT-ECNM response criteria (IWG criteria) are the current clinical and regulatory standard for evaluating treatment response in patients with advanced SM, and are primarily based on the resolution of organ damage. With the development of a potent and selective KIT D816V inhibitor, new PPR criteria were established by global SM experts in collaboration with Blueprint Medicines to measure objective reductions and elimination of neoplastic mast cells at the pathological and molecular level. These assessments are used in routine clinical practice, making the criteria more practical in the real-world setting.

In the Phase 1 EXPLORER trial, 53 patients with advanced SM were treated with AYVAKIT and evaluable for response per modified IWG criteria as of a data cutoff of May 27, 2020. The overall response rate (ORR) was 75 percent, and the rate of complete remission with full or partial hematologic recovery (CR/CRh) was 36 percent per modified IWG criteria, consistent with previously reported data. In the same population, the ORR was 77 percent and the CR/CRh rate was 47 percent per PPR criteria. Twenty-five percent of patients had a molecular CR/CRh, with no measurable evidence of residual KIT D816V mutation in the blood or bone marrow. Importantly, patients with a PPR response at six months had significantly improved OS (p=0.013). In the EXPLORER trial, AYVAKIT was generally well-tolerated, and safety data were consistent with previously reported results.

"For patients with advanced systemic mastocytosis, our primary treatment goals are to rapidly reduce their mast cell burden, improve quality of life, and importantly, prolong survival," said Jason Gotlib, M.D., M.S., Professor of Medicine, Hematology, at the Stanford Cancer Institute and an investigator on the EXPLORER trial. "To advance clinical research, it is important to establish objective measures of response that correlate with clinically significant outcomes and can be broadly incorporated into medical practice. The development of pure pathologic response criteria is a promising approach for assessing treatment response to avapritinib and its impact on survival, and clinically validates the role of KIT D816V inhibition in advanced mast cell disease."

Highly Sensitive Blood-Based Droplet Digital Polymerase Chain Reaction (ddPCR) Test Detects KIT D816V Mutation in 95% of Patients

Registry data have shown a median delay of nine years from symptom onset to diagnosis in patients with non-advanced SM,1 highlighting the need for new diagnostic tools.

In Part 1 of the PIONEER trial of AYVAKIT in patients with non-advanced SM, the sensitivity of ddPCR and next-generation sequencing (NGS) KIT D816V testing was evaluated. As of a data cutoff of December 27, 2019, in all 39 enrolled patients who received testing, a blood-based ddPCR test identified the KIT D816V mutation in 95 percent of patients, compared to 28 percent of patients evaluated by an NGS test performed on bone marrow aspirates. In addition, the ddPCR-based KIT D816V test was more sensitive compared to measurements of serum tryptase (77 percent) and bone marrow mast cells (90 percent) using standard World Health Organization diagnostic criteria. These results highlight the clinical value of blood-based, ddPCR-based KIT D816V testing as a confirmatory diagnostic tool to facilitate identification of patients with non-advanced SM, and a non-invasive screening tool for identifying patients with suspected advanced SM that requires a confirmatory bone marrow biopsy.

SM Patients Reported Worse Physical Functioning and Mental Health Compared to Historical Data for Patients with Lung and Colorectal Cancer

SM is characterized by unpredictable, severe and life-threatening complications despite best supportive care. To better understand the burden of disease, Blueprint Medicines is collaborating with clinical experts on the TouchStone survey, a study of adults with SM (n=56), and allergists/immunologists (n=60) and hematologists/oncologists (n=59) who care for patients with SM.

The TouchStone survey showed that SM symptoms have a profound impact on patients' daily functioning, mental health, and ability to work or perform usual activities. Compared to prior research on colorectal and lung cancer patients, participants reported worse physical functioning and mental health based on the 12-item Short Form Survey (SF-12) questionnaire, a valid and widely used health status measure. More than half of patients (54 percent) reported reduced hours at work, and 32 percent filed for medical disability due to their SM. Respondents cited the use of multiple over-the-counter and prescription medications, and frequent visits to physician specialists and the emergency department to manage their SM. In a one-year period, 30 percent of participants reported going to the emergency room at least once for anaphylaxis.

Healthcare providers broadly recognized the high disease burden in SM. A majority reported that non-advanced SM patients under their care feel depressed or discouraged, and limit their activities due to pain or discomfort. For healthcare providers, the most important treatment goals for advanced and non-advanced SM are improved progression-free survival and OS, and better quality of life.

Copies of Blueprint Medicines data presentations from the ASH annual meeting are available in the "Science--Publications and Presentations" section of the company's website at www.BlueprintMedicines.com.