Italfarmaco has its eyes set on bringing a new treatment that targets the underlying mechanism of the blood disorder Polycythemia Vera.
Milan, Italy-based Italfarmaco has its eyes set on bringing a new treatment that targets the underlying mechanism of the blood disorder Polycythemia Vera.
At the American Society of Hematology (ASH) meeting in Atlanta last week, Italfarmaco unveiled positive safety and efficacy data from two Phase II trials testing the company’s proprietary histone deacetylase (HDAC) inhibitor Givinostat in patients with Polycythemia Vera. Givinostat treatment reduced the levels of mutated Janus Kinase 2 (JAK2), a key underlying cause of the disease, by 25 percent in over 40 percent of the patients.
Company data shared at ASH showed patients on a twice-per-day dose of 100 milligrams of the HDAC inhibitor achieved an overall response rate of 80 percent. That high dose significantly reduces key disease symptoms, the company said. Givinostat reduced the risk of thrombosis according to trial data. Data shows 67 percent of patients saw a reduction in pruritus (itchiness), a key symptom. Polycythemia Vera is a rare blood disease characterized by an increased number of red blood cells, white blood cells and platelets. The increase in those blood cells thickens the blood and significantly raises the risk for thromboembolic and hemorrhagic complications.
As a result, the company will pursue a Phase III trial, Paolo Bettica, head of research and development at Italfarmaco told BioSpace. If it’s approved for Polycythemia Vera, the drug could change the standard of care for those patients. Current treatment options include low-dose aspirin or a JAK inhibitor like Incyte’s Jakafi (ruxolitinib). However, those treatments only address symptoms of the disease. Bettica stressed that Givinostat is targeting the underlying causes of Polycythemia Vera.
“Polycythemia Vera patients have limited treatment options. Those they have only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication” Bettica said.
In a telephone interview from his office in Milan, Bettica said the company will engage with the U.S. Food and Drug Administration as well as the European Medicines Agency on the protocols of the late stage trial. He said the company hopes to begin recruiting for the trial by the end of 2018.
For the data released at ASH, Italfarmaco opted to go with a dose escalation after working with Givinostat for several years, Bettica said.
“With the lower doses we had responses of 50 to 60 percent, but we believed we had room to increase the dose,” he said. “We knew we had room to go higher with the dose. We had experience with a number of studies with Givinostat and we knew what to look for.”
That knowledge seems to be paying off from the data shared at ASH. Additionally, Italfarmaco said the Givinostat efficacy has been supported by more than four years’ worth of data, which the company said shows it is a durable treatment. Givinostat is designed to inhibit the proliferation of cells bearing the JAK2V617F mutation. Givinostat may represent a novel disease modifier in Polycythemia Vera, which current available standard of care is limited to only reducing the symptoms rather than targeting the underlying disease mechanism, the company said.
Italfarmaco is also investigating Givinostat in a Phase III in Duchenne Muscular Dystrophy and a Phase II clinical trial in Becker Muscular Dystrophy. Bettica said in the Phase II DMD trial researchers saw the drug was intervening on the effects of the disease at the muscle level. Bettica said the company hopes the efficacy and tolerability results will continue through the Phase III trial.
Italfarmaco has not placed all of its eggs in the Givinostat basket though. In November, the company filed for approval of Teglutik, the first liquid formulation of Riluzole, which is the only drug approved to treat amyotrophic lateral sclerosis (ALS). Bettica said having a liquid formulation of the drug will be important for many ALS patients due to difficulty of swallowing.
With headquarters in Milan, Italfarmaco has a presence in more than 40 companies through various subsidiaries, such as ITF Pharma in the United States. Bettica said Italfarmaco could soon open a new subsidiary in Germany, but did not provide any details as to the possible expansion.
“Our expansion has been prominent in the past few years,” he said.
