MILAN—Italfarmaco Group has announced an article published in Blood Cancer Journal, outlining interim analysis results from a four-year mean follow-up in 51 patients with polycythemia vera (PV), a type of hematological malignancy belonging to BCR-ABL1-negative chronic myeloproliferative neoplasms (MPNs). The results show a long-term benefit in PV patients treated with givinostat, the company’s histone deacetylase (HDAC) inhibitor. 

The study covers the overall long-term data from patients who were a part of three Phase 1/2 studies, and data from a compassionate use program. The data preliminarily support the long-term use of givinostat.

“These long-term results support the potential of givinostat as a disease-altering treatment in patients with PV who are currently confined to symptomatic care,” stated Dr. Alessandro Rambaldi, professor of Hematology at the University of Milan; head of the Hematology and Bone Marrow Transplant Unit at ASST Papa Giovanni XXIII in Bergamo, Italy; lead author of the study; and lead investigator of the trial. “The overall response rate, which continues to be persistent over the four-year mean follow-up, combined with the good safety profile, justifies the global pivotal Phase 3 study — which will start this year — to further evaluate givinostat and generate clinical evidence necessary to bring the drug to patients.”

Polycythemia vera is a rare blood disease characterized by an overproduction of red blood cells, white blood cells, and platelets. The disease thickens the blood and increases the risk of blood clots. In up to 95% of patients, PV is associated with a mutation in the Janus Kinase 2 (JAK2) gene.

The results published in the article summarize the four-year mean follow-up of an open-label, long-term study that enrolled patients with PV who received clinical benefit from givinostat in the company’s previous three Phase 1/2 clinical trials, and/or on compassionate use. These patients continued to receive givinostat at the last effective and tolerated dose. 

The follow-up analyses showed that givinostat had a good overall safety and tolerability profile. During the study, only five patients (10 percent) experienced Grade 3 adverse events (AEs); no treatment-related Grade 4 or Grade 5 AEs occurred, which supports the safety profile reported in previous analyses. Over 80 percent of the patients responded to treatment, according to the European LeukemiaNet (ELN) response criteria, and this response was maintained for the duration of the follow-up period.

A reduction in the mean JAK2 allele burden was also regularly observed at annual patient visits. The majority of the PV patients continued treatment with givinostat after the conclusion of the study period, as they were receiving relevant clinical benefit — supporting the therapy’s long-term use.

“With over 100,000 polycythemia vera cases in the US and considering that these patients have an increased risk of developing myelofibrosis or acute myeloid leukemia, in addition to the day-to-day complications caused by the disease, the data announced today provide PV patients with hope for a new treatment option,” added Dr. Srdan Verstovsek, professor of Medicine, chief of section for MPNs at the Department of Leukemia, and director of the Clinical Research Center for MPNs at MD Anderson Cancer Center. “I value the opportunity to participate in the upcoming pivotal and global Phase 3 trial, which will be the first of its kind in PV.”

Italfarmaco expects to initiate its global Phase 3 trial with givinostat in PV patients by mid-2021, with over 100 participating sites in Europe, the US, Canada, and Asia.