Merck Initiates Phase 3 Trial of Bomedemstat for Essential Thrombocythemia
Key Insights
Merck (search) has begun the Phase 3 Shorespan-007 trial to assess bomedemstat, an oral LSD1 (search) inhibitor, in essential thrombocythemia (search) (ET) patients without prior cytoreductive therapy.
The trial will compare bomedemstat to hydroxyurea, the current standard of care, aiming to improve disease control and quality of life for ET patients.
Shorespan-007 is a randomized, double-blind study enrolling 300 patients globally, with the primary endpoint being durable clinicohematologic response rate (CHR).
Merck (search) has announced the initiation of the Phase 3 Shorespan-007 clinical trial to evaluate bomedemstat for the treatment of essential thrombocythemia (search) (ET) in patients who have not previously received cytoreductive therapy. This trial marks a significant step in addressing the unmet needs of ET patients, as the current standard of care has remained largely unchanged for decades.
The Shorespan-007 trial is a randomized, double-blind, active comparator-controlled study that will enroll approximately 300 patients globally. Participants will be administered bomedemstat and hydroxyurea placebo or hydroxyurea and bomedemstat placebo for up to 52 weeks. The primary endpoint of the study is the durable clinicohematologic response rate (CHR). Key secondary endpoints include the Myelofibrosis (search) Symptom Assessment Form version 4.0 (MFSAF v4.0) individual fatigue symptom item score, Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a total fatigue score, and MFSAF v4.0 total symptom score. Additional secondary endpoints include duration of hematologic remission, event-free survival (EFS), and disease progression rate (DPR).
Gregory Lubiniecki, MD, VP, global clinical development, Merck (search) Research Laboratories, stated, "The standard of care in essential thrombocythemia (search) has remained unchanged for decades, and patients are in need of new options that have the potential to not only improve disease control, but also improve their quality of life." He further added, "We are rapidly advancing our clinical development programs with the goal of helping to address these unmet needs and bring more options to patients living with myeloproliferative neoplasms (search)."
Bomedemstat: An Investigational LSD1 Inhibitor
Bomedemstat (MK-3543) is an investigational, orally available, small molecule, irreversible lysine-specific demethylase 1 (LSD1 (search)) inhibitor. LSD1 regulates the proliferation of hematopoietic stem cells and plays a crucial role in cell differentiation and maturation. Bomedemstat is currently being evaluated in various myeloproliferative neoplasms (search) (MPNs), including ET, myelofibrosis (search) (MF), and polycythemia vera (search) (PV).
Shorespan-006 Trial
In addition to Shorespan-007, bomedemstat is also being investigated in the Phase 3 Shorespan-006 trial. This global, randomized, open-label, active comparator-controlled study is evaluating bomedemstat compared to the best available therapy in approximately 300 patients with ET who have an inadequate response to or are intolerant of hydroxyurea. The primary endpoint of this study is durable clinicohematologic response, with secondary endpoints including duration of clinicohematologic response, duration of hematologic remission, DPR, and EFS.
Regulatory Designations
Bomedemstat has received Orphan Drug and Fast Track designations from the FDA for ET and MF, as well as Orphan Drug Designation for the treatment of acute myeloid leukemia (search). It also holds a Priority Medicines scheme designation by the European Medicines Agency for the treatment of MF.
Essential Thrombocythemia: Disease Burden
Essential thrombocythemia (search) is a chronic, rare blood disorder characterized by an overproduction of platelets in the bone marrow. This can lead to an increased risk of blood clots, stroke, heart attack, or pulmonary embolism. According to the Leukemia & Lymphoma Society, the incidence of ET is approximately 2.2 per 100,000 population annually, with a prevalence rate of an estimated 24 cases per 100,000 population. The median age at diagnosis is between 60 and 65 years, and it is more common in women, with a 2:1 ratio.
Prior Clinical Data
Updated data from the Phase 2b Shorespan-003 trial, including first-time genomic data, were presented at the American Society of Hematology (ASH) Annual Meeting in December 2023. The Shorespan-003 trial is one of multiple Phase 2 clinical trials where bomedemstat is being evaluated alone and in combination for the treatment of MPNs such as ET, MF and polycythemia vera (search) (PV).