Exclusive: Kenneth Sake from Blueprint Medicines in an Enlightening Conversation with PharmaShots

Highlights:

Systemic mastocytosis (SM) is a rare disease caused by the abnormal accumulation of mast cells – a key part of the body’s immune system

People with SM face potentially debilitating symptoms, such as skin lesions, diarrhoea, bone pain, fatigue and anaphylaxis, which can present challenges across various aspects of patients’ lives

For more than a decade, Blueprint Medicines has partnered with the SM community to advance the scientific understanding and treatment of patients living with this disease

To further characterise the burden of SM, Blueprint Medicines worked with European clinical experts and advocacy groups to conduct the Perceptions Reality and Insights on Systemic Mastocytosis (PRISM) study, which involved 540 patients with a self-reported SM diagnosis and 618 healthcare providers (HCPs) experienced in managing SM

Kenneth Sake, Head of International Medical Affairs at Blueprint Medicines, speaks to PharmaShots about gaps in diagnosis and patient care, including challenges like anaphylaxis reactions and high use of polypharmacy

Saurabh: The PRISM study reveals that many systemic mastocytosis (SM) patients experience a significant impact on their ability to work. Could you elaborate on these findings, the specific challenges patients face in the workplace due to SM symptoms and how this affects their overall well-being?

Kenneth: The PRISM study showed that SM patients faced significant disruption across many aspects of their daily lives, including their careers. Overall, 59% of patients reported that living with SM significantly impacted their ability to work, with many having to reduce their hours (34%), voluntarily quit their job (14%), take medical disability (18%) or take early retirement (8%). These findings are particularly significant given the mean age of patient respondents was 44 years old, which is typically considered within people’s prime working years.

HCPs broadly recognised the effects of SM on their patients’ professional lives, with 58% reporting patients lost employment opportunities as a result of the disease. In addition, HCPs said their patients frequently experienced pain that limited their daily activities, and often had trouble focusing at work or home. These challenges represent some of the likely roadblocks for patients in the workplace.

The PRISM survey showed that people with moderate-to-severe forms of indolent systemic mastocytosis (ISM) – a common type of SM – often had reduced work capacity, compared to those with mild ISM.Mild, moderate and severe classifications were based on total symptom scores assessed by a patient-reported outcome tool, which evaluated 11 distinct symptoms associated with ISM. The correlation between total symptom score and the ability to perform work activities suggests that a range of symptoms may be impacting patients’ employment status.

The PRISM results corroborate a prior survey of U.S. patients recruited from Blueprint Medicines' Mast Cell Connect Registry. This study reported that cognitive symptoms, such as concentration problems, hinder the work productivity of patients with SM. In addition, the survey highlighted that the sudden onset of gastrointestinal issues or anaphylaxis may make it difficult for patients to perform their work responsibilities.

Saurabh: Despite using multiple medications, many patients in the study reported experiencing anaphylactic episodes. How does this ongoing risk of severe allergic reactions shape the daily lives of those living with SM, and what are the psychological impacts of this constant threat?

Kenneth: Life-threatening anaphylaxis represents one of the scariest and most challenging impacts of living with SM. In the PRISM survey, 51% of SM patients reported experiencing anaphylactic episodes during the prior year; within this population, 27% reported five or more episodes in that period.

Triggers, or what may cause SM symptoms, can vary among those affected and may even change over time. In the PRISM study, patients with ISM cited food, medication and temperature changes as several of the most common triggers of anaphylactic reactions. Additional triggers may include fragrances, heat exposure and physical/emotional stress. We have often heard from patients who say they live in a state of heightened awareness over their external surroundings, striving to avoid triggers as much as they can. In certain cases, anaphylactic episodes may even occur without a known trigger.

From ongoing interactions with the SM community, we hear that patients frequently make compromises to try to control their disease, such as limiting their daily activities or isolating themselves to protect against unpredictable triggers. In the PRISM study, HCPs reported that many patients felt anxious about leaving their homes due to the disease. Patients also cited a range of psychological effects from living with SM, such as difficulty sleeping, anxiety/depression and headache/migraine.

Saurabh: PRISM data show a high use of polypharmacy in SM patients. Could you discuss these results, the implications of managing multiple medications, and how this affects the patient experience?

Kenneth: The PRISM study further characterised the significant polypharmacy use among SM patients: on average, patients reported that they currently receive seven treatments and have used 10 medicines to manage the disease over their lifetime. Notably, PRISM data showed a correlation between high ISM symptom severity – based on total symptom scores – and increased polypharmacy use. This finding suggests that patients with moderate-to-severe ISM need more effective therapy.

In PRISM, 24% of patients reported medication as a common trigger for anaphylaxis reactions, a finding that validates results from the previously cited U.S. survey. In that study, patients reported concerns about drug-drug interactions and the long-term effects of antihistamines – a frequently used treatment – on their cognition. We also hear from the SM community that it can be challenging to manage the varying dose schedules associated with complex treatment regimens, and that patients may even need to plan their daily activities around their medication use. As a result, patients have reported that reducing the number and types of treatment they receive can be an important therapeutic goal.

Saurabh: The study highlights the lengthy and complex diagnostic journey for SM patients. What factors contribute to this delay in diagnosis, and what are the potential consequences for patients who go undiagnosed or misdiagnosed for extended periods? 

Kenneth: We frequently hear from the SM community about the challenges of receiving a diagnosis, which is further corroborated by PRISM findings. In the study, the time from symptom onset to diagnosis was more than a year in the majority of patients, and more than five years for 19% of patients. There are several contributing factors:

SM can involve a diverse range of non-specific symptoms, which may not be recognised as driven by a single disease. Because SM symptoms involve multiple organ systems, healthcare specialists may initially address issues related to their focus area (e.g., skin effects for dermatologists, GI effects for gastroenterologists), without always connecting the patient’s different symptoms to a common underlying cause.
Multiple SM symptoms can overlap with those associated with other conditions, such as allergic or gastrointestinal disorders, making it more challenging to recognise the underlying disease.

Due to the rarity of SM, HCPs may not be familiar with the disease.

Reinforcing these challenges, PRISM study data show that at the time of diagnosis, HCPs reported that patients presented with an average of 18 symptoms. In addition, patients visited an average of four HCPs before the disease was detected. These PRISM findings highlight the need to continue raising awareness of SM across key specialties, including haematologists, oncologists, allergists, dermatologists and gastroenterologists. We are also focused on advancing screening tools that help clinicians determine who is at increased risk of SM, so that further diagnostic workup may then be performed.

It is critical that patients receive a timely diagnosis, so that they may be referred to specialists knowledgeable about caring for this disease. A subset of SM patients has advanced forms of the disease, which is characterised by organ damage that typically requires care from a haematologist/oncologist. For patients with ISM, emerging evidence has shown that disease symptoms can worsen over time and may ultimately lead to serious health consequences, such as impacts on bone health. As a result, we hear from clinicians that there is an urgency to diagnose and treat a range of patients across the spectrum of the disease.

Saurabh: The PRISM study shows a disconnect between the time HCPs first see a patient and the eventual diagnosis of SM. What steps can be taken to bridge this gap and ensure earlier diagnosis and intervention for individuals with SM?

Kenneth: In close partnership with the clinical community, we are looking to address this challenge using a multi-pronged approach:

Educating HCPs on hallmark disease symptoms: The PRISM study reinforces that patients may present with a diverse range of symptoms spanning multiple organ systems. In disease awareness efforts, we have highlighted three hallmark symptoms that are frequently present in SM – skin lesions, anaphylaxis and diarrhoea. Using this approach, our goal is to educate healthcare specialists on how the symptoms from different organ systems may have a common underlying cause, so if they suspect a patient may have SM, they can pursue appropriate diagnostic testing.
Highlighting patient populations with increased likelihood of having SM: We recently conducted the PROSPECTOR study, which found that patients with certain mast cell activation symptoms were 400 times more likely to have the KIT D816V mutation – the primary driver of SM and other clonal mast cell diseases – than the general population. This research highlights our efforts to partner with global medical centres and help identify patients that are at elevated risk of having SM.
Generating evidence on non-invasive screening tools: In data reported at the American Society of Hematology (ASH) 2024 Annual Meeting, we showed that non-invasive, blood-based assays demonstrated high levels of sensitivity for detecting KIT D816V. Screening tools have the potential to help clinicians determine who should receive a bone marrow biopsy, which is needed for a definitive diagnosis based on the World Health Organization (WHO) SM clinical guideline.

Saurabh: What programmes offline and digital are being organised by Blueprint Medicines to support improving awareness among patients and caregivers about SM? 

Kenneth: We recently introduced the online patient education portal, Navigating SM, with the goal of providing people living with SM and caregivers the tools and resources to encourage self-advocacy and shared decision-making with HCPs. The portal features disease information that reflects the PRISM study findings, including the wide range of possible symptoms and the diverse specialists who may be involved in SM care, among other topics. In the future, we plan to add stories of people living with SM to help others realise they are not alone in facing the physical, psychological and emotional impacts of the disease.

It is essential that we work closely with patient organisations and support their ongoing efforts to educate, engage and empower people living with SM. We have recently hosted quarterly exchanges with patient group representatives across European countries, where expert speakers outside the field of SM have been invited to discuss key topics, such as HCP/patient communications, health literacy and shared decision-making. The hope is that by gaining insights from patient advocates around common areas of interest, we can help foster education on new ways to support their respective communities, and these groups can learn about successful approaches from others.

About the author

Kenneth Sake

Kenneth Sake has led the International Medical Affairs team at Blueprint Medicines since September 2023. He holds a medical degree and an MBA from the University of Antwerp in Belgium, and he is a member of the Belgian society of Pharmaceutical medicine.

Kenneth has been working in the biopharmaceutical industry for 31 years in various roles, mainly in medical affairs. He has been medical director in Belgium, the Netherlands and the UK & Ireland in the past, and has led different product and indication launches in Neurology and Allergology from a country, European and global perspective by driving strategy in a cross-functional way.

He brings extensive experience in developing, leading and coordinating large teams on a global as well as European level, and has been regularly involved in driving change processes within the medical affairs organization.

Kenneth is passionate about translating scientific data into patient solutions through intensive collaboration with both internal and external stakeholders. Throughout his career, he experienced the importance of innovation, communication, transparency and collaboration between stakeholders to optimize individual patient outcomes. 