Nicolas Paquette-Lamontagne, VP, Medical Affairs at Blueprint Medicines Shares his Views on Clinical Data of Ayvakit for Patients with Systemic Mastocytosis

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Nicolas Paquette-Lamontagne, VP, Medical Affairs at Blueprint Medicines Shares his Views on Clinical Data of Ayvakit for Patients with Systemic Mastocytosis


  • Nicolas discussed about Systemic Mastocytosis as a disease and highlighted its epidemiology & other details. He also spoke about the clinical data of avapritinib presented at the ASH’22 Annual Meeting    

  • Nicolas also shared the key findings from the PATHFINDER and EXPLORER trial evaluating avapritinib and the rationale behind conducting two different trials 

  • This interview gives an understanding of how Blueprint Medicines is developing life-changing therapies for people with cancer and blood disorders  

Smriti: Can we first discuss Systemic Mastocytosis (its epidemiology, prognosis, available treatment options, and unmet needs)  

Nicolas Paquette-Lamontagne: Systemic mastocytosis (SM) is a rare hematological disorder that results in the uncontrolled activation and proliferation of mast cells across multiple organ systems. In SM, activated mast cells release histamine and other proteins that promote allergic reactions, inflammation, and other immune responses, and people living with the disease. These effects can profoundly impact the quality of life, as patients can. 

In Europe, there are approximately 40,000 people living with SM. Of this population, 90 to 95% of patients are estimated to live with non-advanced (indolent or smoldering) SM, which has no currently approved therapies. Five to 10% are thought to live with advanced SM, which occurs when the proliferation of mast cells leads to organ damage. Across advanced SM subtypes, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL), patients have historically had limited treatment options to address their disease and poor survival. Traditional therapies have included multi-kinase inhibitors, chemotherapy, and symptom-directed treatments. There is a need for new therapies that selectively target the underlying mutation, KIT D816V, to improve outcomes and quality of life for people living with SM.  

KIT D816V was the first target Blueprint Medicines’ founders sought to address. Today, we continue to remain committed to better understanding SM and pioneering methods for accelerating diagnosis and advancing treatment.  

Smriti: Explain the details of avapritinib in SM (MOA, ROA, formulations, and other details)  

Nicolas Paquette-Lamontagne: Avapritinib is an oral, highly potent, and selective inhibitor of KIT D816V, approved in the USA and the EU based on results from the Phase 1 EXPLORER study and Phase 2 PATHFINDER study. AYVAKYT® (avapritinib) is approved by the European Medicines Agency (EMA) for the treatment of adult patients with ASM, SM-AHN, and MCL, after at least one systemic therapy, and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harbouring the PDGFRA D842V mutation. AYVAKIT® (avapritinib) is approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with advanced SM, including patients with ASM, SM-AHN, or MCL, and adults with unresectable or metastatic GIST harbouring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. Please click here to see the full U.S. Prescribing Information for AYVAKIT, and click here to see the European Summary of Product Characteristics for AYVAKYT. AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S. or Europe.  

Blueprint Medicines is pursuing regulatory approval for licensing for the treatment of advanced SM in additional geographies. 

Smriti: Highlight the clinical data of avapritinib for the treatment of advanced systemic mastocytosis presented at the ASH Annual Meeting  

Nicolas Paquette-Lamontagne: At ASH, we highlighted long-term follow-up data from the EXPLORER and PATHFINDER trials of avapritinib in patients with advanced SM. The PATHFINDER presentation focused on the clinical profile of avapritinib as a first-line treatment in advanced SM, including the most common subtype of SM-AHN. The EXPLORER presentation reported on the ongoing survival benefits of avapritinib, with up to six years of patient follow-up, in advanced SM. Both datasets reinforced the favorable benefit-risk profile of avapritinib in this patient population. 

In addition, the PATHFINDER presentation cited a retrospective analysis showing the survival benefits of avapritinib when indirectly compared to real-world data from alternative available therapies. Real-world evidence generated by this study helped the EMA interpret single-arm EXPLORER and PATHFINDER trial findings, reflecting the growing use of real-world data in regulatory decision-making.  

Smriti: What were the key findings from the PATHFINDER and EXPLORER trial evaluating avapritinib? 

Nicolas Paquette-Lamontagne: In the PATHFINDER trial data reported at ASH, avapritinib showed broad clinical activity across treatment-naïve patients with advanced SM, further demonstrating its impact in the first-line treatment setting. In response-evaluable patients, the overall response rate (ORR) was 84%, with 32% experiencing complete remission (CR) or complete remission with partial hematologic recovery (CRh), 48% experiencing partial remission, and 4% experiencing clinical improvement. The median duration of response (DOR) has not been reached, and the estimated 24-month overall survival (OS) rate was 88%. For evaluable patients with the most common advanced SM subtype, SM-AHN, the ORR was 95%, the rate of CR/CRh was 37% and the estimated 24-month OS rate was 86%. 

In previously reported analyses, patients have shown rapid and deep responses to avapritinib treatment regardless of prior therapy, advanced SM subtype, or presence of high-risk mutations. Updated data from the EXPLORER trial reinforce prior findings in patients with or without prior therapy. In evaluable patients, the ORR was 77%, with median DOR and OS not yet reached in patients who were followed for up to six years, reflecting durable clinical outcomes. 

Across both presentations, safety results were consistent with previously reported data. The most common treatment-related adverse events (AEs) included edema, thrombocytopenia, anemia and nausea. Discontinuations due to treatment-related AEs occurred in four treatment-naïve patients (11%) since the initiation of the PATHFINDER trial in 2018, and seven patients across lines of therapy (10%) since the initiation of the EXPLORER trial in 2016. 

Smriti: Can you share with us the reasons for evaluating avapritinib in advanced SM under two different trials? 

Nicolas Paquette-Lamontagne: The Phase 1 EXPLORER study was designed to assess safety, define a recommended dosing regime, and evaluate the clinical activity of avapritinib. The Phase 2 PATHFINDER study was conducted to further evaluate the safety and efficacy of avapritinib at the dose of 200 mg once daily, and trial results confirmed the findings from the EXPLORER trial. In the PATHFINDER trial, a prespecified interim analysis was designed to demonstrate the efficacy of avapritinib in patients with advanced SM who had sufficient follow-up for response evaluation. Global regulatory applications in advanced SM were based on results from both the EXPLORER and PATHFINDER trials.  

In each trial, efficacy assessments were conducted in evaluable patients based on stringent response criteria (modified IWG-MRT-ECNM, or International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis). Based on these criteria, patients required a sustained response with 12-week confirmation and full resolution of one or more clinical findings. 

Since initiating SM clinical development in 2016, Blueprint has amassed a comprehensive therapeutic dataset in patients with this rare disorder, highlighting our long-term commitment to improve clinical outcomes across the spectrum of disease. 

Source: Illness.com  

About the Author:   

Nicolas Paquette-Lamontagne is the VP, Medical Affairs at Blueprint Medicines. He has over 20 years of industry and clinical experience in orphan/rare diseases, oncology and cystic fibrosis.  

Nicolas holds a MSc and Pharmacy Baccalaureate (BPharm) qualifications from the Université de Montréal, Canada and a MBA from McGill University. He has been on the editorial board for Québec Pharmacie (A French-Canadian pharmaceutical journal); and a scientific reviewer/abstract writer for The Annals of Pharmacotherapy Journal.    

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Senior Editor at PharmaShots. She is curious and very passionate about recent updates and developments in the life sciences industry. She covers Biopharma, MedTech, and Digital health segments along with different reports at PharmaShots.

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