Exciting news was revealed on June 18, 2014 with the announcement the Mocetinostat Orphan Drug Designation from the FDA. Information gleaned from a Phase 1/2 study of Mocetinostat showed that when used alongside Azacitidine (Vidaza) this combination provided efficacious treatment for patients with myelodysplastic syndromes. Patients who were at intermediate or high risk myelodysplastic syndromes, also known as MDS demonstrated a high response rate to this dynamic duo. Roughly 64 percent of patients with MDS who were administered both Azacitidine and Mocetinostat showed a viable response to the treatment, and a startling 50 percent of patients achieved a complete response. Addtionally, 33 percent of patients gained transfusion independence after their treatment regimen with Azacitidine and Mocetinostat. Although Vidaza (Azacitidine) has been proven effective independently of Mocetinostat, the addition of this drug has offered a sizable increase in response rate, particularly in high risk MDS patients. A Phase I trial is currently underway to determine the safety, tolerability and efficacy of Mocetinostat and Azacitidine, although the planned dosage of Mocetinostat will be slightly lower in than was administered during the 1/2 trial phase.
Study results from 22 patients with MDS made up the data for the 1/2 trial of Azacitidine and Mocetinostat. These patients were considered as intermediate and high risk, as they possessed either refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2. The average age of the clinical trial participants was 72 years old, with 64 percent of the patients having blast counts between 10 and 20 percent. The majority of patients had received no previous first line therapy, while a little over 40 percent of the participants had received therapy but not with Azacitidine or Mocetinostat. When the ½ trial commenced patients were administered 75 mg/m2 of Azacitidine subcutaneously. This protocol lasted for the first seven days of a 28-day cycle of treatment. Roughly 80 percent of the participants were dosed with 90 milligrams of Mocetinostat three times per week during the 28 day cycle, beginning on the fifth day of treatment with Azacitidine. The remaining 20 percent of patients received a 110 milligram or 135 milligram dose of Mocetinostat on the same schedule. After 4.5 cycles of treatment positive results emerged, with half of all participants achieving a complete response. Additionally, 5 percent of people displayed improvements in their blood cell counts. Low platelet counts, diarrhea and fatigue dominated the side effects, however no catastrophic adverse events occurred. Over 447 patients in 13 clinical trials have received treatment with Mocetinostat, which have overall been encouraging. There are 28 patients documented to have achieved a 93 percent disease control rate thus far, and the number is expected to increase as continued research and development plays out.
As a histone deacetylase inhibitor Mocetinostat works by raising the production of proteins in the body which cause cell death and slow cell division. Myelodysplastic syndromes are cancerous conditions that typically occur when the blood-forming cells in the bone marrow become damaged. The unfortunate damage leads to lower numbers of one or several types of blood cells, and many of the blood cells formed by the damaged bone marrow cells are ultimately considered defective. About one-third of patients see their diagnosis of MDS progress quickly to acute myeloid leukemia. Research and development of new and effectual treatments to combat myelodysplastic syndromes is urgent.
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