Phase 3 Trial of Bomedemstat in Essential Thrombocythemia Begins Enrollment

Posted on September 17, 2024September 17, 2024 by mpn_admin

September 12, 2024

By Sabrina Serani

Fact checked by Jordyn Sava

A pivotal phase 3 trial (NCT06456346) has initiated to evaluate bomedemstat (MK-3543; IMG-7289), an investigational agent for the treatment of patients with essential thrombocythemia (ET) who have previously not received cytoreductive therapy.¹

“The standard of care in essential thrombocythemia 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,” said Gregory Lubiniecki, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “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.”

The Shorespan-007 trial will compare the orally available LSD1 inhibitor bomedemstat with standard-of-care hydroxyurea in patients with treatment-naive ET, the most common myeloproliferative neoplasm. LSD1 is an enzyme that is potentially important for regulating the proliferation of hematopoietic stem cells, as well as the maturation of progenitor cells.

The study’s primary end point is durable clinicohematologic response rate, and secondary end points include duration of hematologic remission, event-free survival, incidence of adverse events, and disease progression rate. Additionally, investigators will be patient-reported outcomes, including fatigue and symptoms.

The FDA previously granted orphan drug and fast track designations to bomedemstat in ET and myelofibrosis, as well as orphan drug designation in acute myeloid leukemia.

Essential Thrombocythemia Trial Launched Evaluating Bomedemstat

Posted on September 9, 2024September 9, 2024 by mpn_admin

August 31, 2024

By Alex Biese

Fact checked by Ashley Chan

A second phase 3 clinical trial has been launched for the investigational oral drug bomedemstat as a potential new treatment for patients with essential thrombocythemia.

The Shorespan-007 clinical trial, according to a news release from bomedemstat manufacturer Merck, will investigate the use of the drug among patients with essential thrombocythemia who have not previously received cytoreductive therapy.

The global trial, which is currently recruiting, will compare bomedemstat to the current standard of care chemotherapy, hydroxyurea. The trial, with 300 participants, is expected to be concluded in May 2029, according to its listing on clinicaltrials.gov.

Essential thrombocythemia, part of a group of blood cancers known as myeloproliferative neoplasms (MPNs), is a rare disease in which the bone marrow produces too many platelets, according to The Leukemia & Lymphoma Society. This disease, The Leukemia & Lymphoma Society explained, can cause blood clots to form in a patient’s blood vessels, in turn resulting in serious health issues such as stroke, heart attack or pulmonary embolism.

“The standard of care in essential thrombocythemia 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,” said Dr. Gregory Lubiniecki, vice president of global clinical development for Merck Research Laboratories, in the company’s news release. “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.”

Merck Announces Phase 3 Trial Initiation for Bomedemstat, an Investigational Candidate for the Treatment of Certain Patients With Essential Thrombocythemia

Posted on August 29, 2024August 29, 2024 by MPN Advocacy & Education

August 27, 2024 6:45 am ET

The initiation of a second Phase 3 clinical trial for bomedemstat demonstrates company’s commitment to advancing research in myeloproliferative neoplasms (MPNs)

RAHWAY, N.J.–(BUSINESS WIRE)– Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of Shorespan-007, a pivotal Phase 3 clinical trial evaluating bomedemstat, an investigational orally available lysine-specific demethylase 1 (LSD1) inhibitor, for the treatment of patients with essential thrombocythemia (ET) who have previously not received cytoreductive therapy. Essential thrombocythemia is a chronic, rare blood disorder and is the most common type of myeloproliferative neoplasm. Global recruitment of the Shorespan-007 trial has begun, with patients now enrolling.

“The standard of care in essential thrombocythemia 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,” said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. “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.”

Shorespan-007 is a Phase 3, randomized, double-blind, active comparator-controlled clinical trial ( NCT06456346 ) evaluating bomedemstat compared to the current standard of care chemotherapy, hydroxyurea, for treatment of patients with ET who have previously not received cytoreductive therapy. The trial will enroll approximately 300 patients globally. The primary endpoint of the study is durable clinicohematologic response rate (CHR). Key secondary endpoints include Myelofibrosis 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 and disease progression rate.

Which Factors Predict Thrombotic Events in Essential Thrombocythemia?

Posted on August 15, 2024August 15, 2024 by mpn_admin

August 13, 2024

The risk for essential thrombocythemia-related events in patients with the disease can be predicted using currently available clinical data, researchers wrote in a letter to the editor appearing in Blood Cancer Journal.

“Although considered the most indolent myeloproliferative neoplasm (MPN), essential thrombocythemia (ET) is linked to burdensome vasomotor symptoms and potentially fatal complications that include thrombosis, hemorrhage, and disease progression to myelofibrosis and aggressive myeloid neoplasms,” Ghaith Abu-Zeinah, MD, a hematologist and oncologist at the Richard T. Silver Myeloproliferative Neoplasms Center at Weill Cornell Medicine, New York, and colleagues wrote. “Prognostic measures to identify those at greatest risk for thrombosis, progression, and death in ET [events] are important for timely risk-adapted intervention with available treatments, and for development of interventional trials to improve event-free survival [EFS]. But predicting risks of events in ET has been difficult because ET is an uncommon and clinically heterogeneous chronic disease.”

Predicting excess mortality and disease progression related to ET presents challenges because such events often occur decades after a patient is diagnosed, the researchers continued.

“Thus, retrospective analysis of large cohorts with sufficiently long follow-up is required to identify prognostic measures to stratify risk in patients with ET,” they wrote.

PharmaEssentia Completes Patient Enrollment for Phase 2b EXCEED-ET Trial in Essential Thrombocythemia and Phase 3b ECLIPSE-PV Trial in Polycythemia Vera

Posted on June 28, 2024June 28, 2024 by MPN Advocacy & Education

June 25, 2024

PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TWSE: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology, oncology and immunology, today announced completion of enrollment for two clinical trials evaluating its ropeginterferon alfa-2b-njft (BESREMi ® ).

The Phase 2b EXCEED-ET trial (NCT05482971), which is evaluating the effectiveness and safety of ropeginterferon alfa-2b-njft in adult patients with essential thrombocythemia (ET), has exceeded the enrollment goal of 64 patients to include 91 patients. EXCEED-ET is evaluating people diagnosed with ET who are either treatment naïve or have received previous ET treatment with hydroxyurea or anagrelide but require a treatment change due to intolerance or because the previous treatment is no longer effective. This trial is being conducted in the United States and Canada and will use the accelerated dosing schedule (250, 350, 500 mcg). This accelerated dosing schedule has been previously assessed in Asian clinical trials.

The Phase 3b ECLIPSE-PV trial (NCT05481151), assessing the effectiveness and safety of two dosing regimens of ropeginterferon alfa-2b-njft in adult patients with polycythemia vera (PV), has also exceeded the enrollment goal of 100 patients to include 111 patients. ECLIPSE-PV is evaluating two ropeginterferon alfa-2b-njft doses, including the accelerated dosing schedule (as described above) in comparison to the current recommended dosing regimen. The ECLIPSE-PV study is being performed in the United States and Canada.

Are thrombosis, progression, and survival in ET predictable?

Posted on June 28, 2024June 28, 2024 by MPN Advocacy & Education

June 25, 2024

Ghaith Abu-Zeinah, Katie Erdos, Neville Lee, Ahamed Lebbe, Imane Bouhali, Mohammed Khalid, Richard T. Silver & Joseph M. Scandura

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) that originates from a hematopoietic stem cell harboring a mutated JAK2, CALR, or MPL gene, or none of these three mutations (10–15% are “triple negative”). Although considered the most indolent MPN, ET is linked to burdensome vasomotor symptoms, and potentially fatal complications that include thrombosis, hemorrhage, and disease progression to myelofibrosis and aggressive myeloid neoplasms. Prognostic measures to identify those at greatest risk for thrombosis, progression, and death in ET (events) are important for timely risk-adapted intervention with available treatments, and for development of interventional trials to improve event-free survival (EFS). But predicting risks of events in ET has been difficult because ET is an uncommon and clinically heterogenous chronic disease. Predicting progression and excess mortality is even more challenging because these events typically occur decades after ET diagnosis [1]. Thus, retrospective analysis of large cohorts with sufficiently long follow-up is required to identify prognostic measures to stratify risk in patients with ET.

Prognostic models have been developed to assess the risk of thrombosis (IPSET-thrombosis [2]) or overall survival (OS) in ET (IPSET-survival [3], MIPSS-ET [4], and triple A [AAA] [5]). This journal recently published two large retrospective ET cohorts: Gangat et al. at the Mayo Clinic (Mayo) [6] and Loscocco et al. at the Florence Center Research and Innovation of Myeloproliferative Neoplasms (CRIMM) [7]. Both studies confirmed previously identified risk factors for thrombosis, progression and/or death in ET that include older age (Age ≥ 60), male sex, elevated white blood cell count (WBC > 11 × 10⁹/L), elevated absolute neutrophil count (ANC ≥ 8 × 10⁹/L), and low absolute lymphocyte count (ALC < 1.7 × 10⁹/L) at the time of presentation. We evaluated these parameters and current risk models in our cohort of 328 adult patients with ET treated at the Weill Cornell Medicine (WCM) Silver MPN Center over a median follow-up of 6 years [8]. This cohort was rigorously defined according to the 2022 World Health Organization diagnostic criteria and therefore all patients had a diagnostic bone marrow biopsy and had alternative diagnoses scrupulously ruled out. The methods of data collection, retrieval, and analysis used were previously described [9], and cohort characteristics are included in Supplementary Table 1.

Prospective Analysis Highlights Patterns of Progression to Myelofibrosis Following Essential Thrombocythemia Diagnosis

Posted on June 19, 2024June 19, 2024 by MPN Advocacy & Education

June 17, 2024

Author(s): Caroline Seymour

Most patients with essential thrombocythemia (95.7%; 1184/1237) included in an analysis of the prospective, observational MOST study (NCT02953704) did not experience disease progression to myelofibrosis, but those who did were found to have had longer duration of disease, higher white blood cell counts, and lower hemoglobin levels at enrollment, according to findings presented at the 2024 EHA Congress.¹

Of the 4.3% (n = 53) of patients who progressed to myelofibrosis, a pathologic diagnosis of the disease or grade 2 or greater fibrosis was the most common indicator (49.1%; n = 26) of disease progression, followed by new or worsening splenomegaly coupled with a combination of high white blood cell counts and low hemoglobin levels and platelet counts (22.6%; n = 12). Additional indicators were death from myelofibrosis, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML; 11.3%; n = 6) and circulating blasts above 1% with new or worsening splenomegaly (5.7%; n = 3); patients also met at least 2 progression criteria (11.3%; n = 6).

“These findings and further analyses of MOST data will add insight into disease progression in patients with essential thrombocythemia and facilitate clinical management of this patient population,” lead study author Ruben A. Mesa, MD, FACP, president and executive director of Atrium Health Levine Cancer Institute and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, and vice dean of cancer programs at Wake Forest University School of Medicine in Charlotte, North Carolina, and coauthors wrote in the poster.

ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options

Posted on March 11, 2024March 11, 2024 by mpn_admin

Published: 04 March 2024

Jean-Jacques Kiladjian, Francisca Ferrer Marin, Haifa Kathrin Al-Ali, Alberto Alvarez-Larrán, Eloise Beggiato, Maria Bieniaszewska, Massimo Breccia, Veronika Buxhofer-Ausch, Olga Cerna, Ana-Manuela Crisan, Catalin Doru Danaila, Valerio De Stefano, Konstanze Döhner, Victoria Empson, Joanna Gora-Tybor, Martin Griesshammer, Sebastian Grosicki, Paola Guglielmelli, Valentin García-Gutierrez, Florian H. Heidel, Arpád Illés, Ciprian Tomuleasa, Chloe James, Steffen Koschmieder, Maria-Theresa Krauth, Kurt Krejcy, Mihaela-Cornelia Lazaroiu, Jiri Mayer, Zsolt György Nagy, Franck-Emmanuel Nicolini, Francesca Palandri, Vassiliki Pappa, Andreas Johannes Reiter, Tomasz Sacha, Stefanie Schlager, Stefan Schmidt, Evangelos Terpos, Martin Unger, Albert Wölfler, Blanca Xicoy Cirici & Christoph Klade

Abstract

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives.

Review Details Current State of Essential Thrombocythemia Diagnosis and Care

Posted on March 11, 2024March 11, 2024 by mpn_admin

Vicki Moore, PhD

March 7, 2024

A review published in the American Journal of Hematology details current aspects of diagnosis, risk stratification, and management of essential thrombocythemia (ET). The review was written by Ayalew Tefferi, MD, of Mayo Clinic in Rochester, Minnesota; Alessandro Maria Vannucchi, MD, of the University of Florence in Florence, Italy; and Tiziano Barbui, MD, of Papa Giovanni XXIII Hospital in Bergamo, Italy.

Regarding ET diagnosis, Tefferi and colleagues highlighted criteria from the International Consensus Classification. This system involves multiple criteria for ET diagnosis, such as thrombocytosis (with a platelet count ≥450×10⁹/L), exclusion of other myeloid neoplasms, and other features, such as possible mutation of JAK2, CALR, or MPL. However, the authors noted, up to 20% of patients having ET might be negative for mutations in all 3 of these genes.

According to data from the Surveillance, Epidemiology, and End Results Registry in the US, the 5-year survival rate among 8768 patients with ET was 88.7%. The median survival time for this population was 12.1 years.

Among risk factors related to survival with ET, the authors considered age to be most important. Additional risk factors identified for survival vary by the risk model being used. The triple A survival risk model, for example, includes absolute neutrophil count and absolute lymphocyte count, in addition to age, and stratifies patients into 4 risk groups with median survival times ranging from 8 years in the high-risk group to 47 years in the low-risk group. The authors emphasized age, presence of a thrombosis history, and presence of JAK2 mutation as risk factors for thrombosis with ET.

In describing their treatment approach to ET, the authors indicated they began with consideration of thrombosis risk stratification, with some treatment options within thrombosis risk groups based on cardiovascular risk.

JNJ-88549968 by Johnson & Johnson for Essential Thrombocythemia: Likelihood of Approval

Posted on February 19, 2024February 19, 2024 by mpn_admin

GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. Attributes of the drug, company and its clinical trials play a fundamental role in drug-specific PTSR and likelihood of approval.

JNJ-88549968 overview

JNJ-88549968 is under development for the treatment of calreticulin (CALR)-mutated myeloproliferative neoplasms, essential thrombocythemia, neoplasms, leukemia and myelofibrosis. The therapeutic candidate is a bispecific antibody acts by targeting calreticulin and CD3.