ITP, or immune thrombocytopenia, is a platelet disorder where the immune system destroys its own platelets by way of destructive antibodies. Platelets are very small blood cells that originate in the bone marrow. Upon injury to a blood vessel, platelets travel to the site and form blood clots to seal the wound. A person with low platelets is at risk for excessive bruising, bleeding, and in severe cases, possible hospitalization or death.
About Rilzabrutinib
As reported recently in MedicalXpress, researchers at Massachusetts General Hospital (MGH) are conducting an international phase I/II clinical trial investigating the oral drug rilzabrutinib. Early results indicate that the drug may raise platelet levels in ITP patients safely and efficiently. The findings have been reported in the NEJM.
Prior research has indicated that macrophages and the Bruton kinase enzyme (BKE) are responsible for the destruction of antibody-coated platelets. Macrophages are cells that detect and destroy harmful organisms. BKE is vital to their functioning.
The FDA approved a BKE inhibitor as a treatment for a type of leukemia, as it has shown to decrease macrophage activity. The drug, called ibrutinib, raises the platelet counts for both ITP and leukemia patients. However, ibrutinib holds a negative for ITP patients due to its inhibiting of platelet function.
A major benefit of oral rilzabrutinib, a new form of Bruton kinase inhibitor, is that it not only reduces the activity of macrophages and anti-platelet antibodies, but unlike other drugs, will not affect platelet function.
About the Trial
The trial consisted of sixty patients and involved various rilzabrutinib doses. Adverse events related to treatment were temporary and minor. A five-month follow-up found a significant platelet response among not only the entire enrollment, but also among the forty percent of patients who began with the maximum dose of rilzabrutinib.
A satisfactory platelet count developed within ten days on average. The trial results indicated that a 400 mg dose taken two times per day would be the preferred dose for additional testing.
It is notable that patients who participated in the study had been treated unsuccessfully with other drugs. Therefore, with respect to treatment, their disorder was considered severely refractory. Currently, a phase III trial is underway at various sites including MGH. In the larger trial, rilzabrutinib’s effectiveness in ITP patients will be tested.
Looking Forward
Dr. David Kuter, of MGH and the lead author of the study, predicts that if rilzabrutinib continues to show similar results in other trials such as its ability to safely increase platelets, the drug may eventually eliminate the antibody that is the cause of the disease. What Dr. Kuter finds most impressive is the lack of negative effects in rilzabrutinib that are usually found in this type of drug. He emphasized an absence of bleeding, liver dysfunction, and infection. The drug was well tolerated.
