Pelabresib, an investigational BET inhibitor, when administered in combination with JAK inhibitor Jakafi (ruxolitinib), has been shown to reduce spleen volume and displayed “a strong positive trend” toward symptom reduction among patients with JAK inhibitor-naïve myelofibrosis in a recent study, according to an announcement from MorphoSys AG, the biopharmaceutical company behind pelabresib.
In the phase 3 MANIFEST-2 study, 66% of patients who received pelabresib with Jakafi achieved at least a 35% reduction in spleen volume at week 24, compared with 35% of patients treated with Jakafi and placebo.
“I believe MANIFEST-2 provides us with valuable evidence that the addition of pelabresib offers meaningful improvements over JAK inhibitor monotherapy as a first-line approach for patients with myelofibrosis,” said Dr. John Mascarenhas, director of the adult leukemia program at The Tisch Cancer Institute at Mount Sinai in New York in the news release. “The pelabresib and (Jakafi) combination therapy significantly reduced spleen volume — the best prognostic indicator we have at our disposal for long-term myelofibrosis patient outcomes. Based on insights from MANIFEST-2, pelabresib represents a promising and well-tolerated therapeutic option for a community in need of innovation.”
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Additionally, patients’ total symptom score (TSS) was reduced by 15.99 points at week 24 from a score of 28.26 at baseline among the cohort of patients treated with pelabresib and Jakafi, compared with a TSS reduction of 14.05 points at week 24 from a baseline score of 27.36 among patients treated with Jakafi plus placebo.
“Myelofibrosis patients experience a severely diminished quality of life due to symptoms such as severe fatigue, night sweats, bone pain and fever — symptoms that can leave them bedridden for days and with limited ability to participate in daily activities. Reducing symptom burden is a primary goal of myelofibrosis treatment,” Dr. Ruben A. Mesa president and executive director, Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina, said in the news release. “Total symptom score assessment is a validated tool to document the challenges that patients encounter on a daily basis. The symptom reduction shown in MANIFEST-2 is an important result that should be strongly considered when evaluating the efficacy of the pelabresib and (Jakafi) combination therapy for myelofibrosis.”
Findings from the MANIFEST study previously published in the Journal of Clinical Oncology showed that among 84 patients who received at least one dose of the pelabresib and Jakafi combination, grade 3 or 4 toxicities were seen in at least 10% of patients, including thrombocytopenia (12%; a low platelet count) and anemia (35%; a low count of healthy red blood cells), with toxicities resulting in treatment discontinuation in three patients. In MANIFEST-02, according to the news release, the pairing’s safety profile “was consistent with the previously observed safety profile of this combination therapy.”
Detailed findings from MANIFEST-2 are scheduled to be presented on Dec. 10 at the 65th American Society for Hematology (ASH) Annual Meeting and Exposition in San Diego, California, and MorphoSys indents to submit a New Drug Application for pelabresib in combination with Jakafi for patients with myelofibrosis to the Food and Drug Administration (FDA) in mid-2024, according to the news release, which noted that the combination received Fast Track Designation from the FDA in 2018.
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