A press release from Aprea Theraputics has just announced the results of a Phase II clinical trial of the drug APR-246 in patients with myelodysplastic syndromes (a group of blood disorders) that involve mutation of the gene TP53.
Myelodysplastic syndromes (MDS) is a collective term for a group of rare blood disorders that reduce the number of healthy red blood cells a person has, often leading to cancer. The disease is most prevalent in people aged 70 to 80. It occurs when bone marrow stops effectively producing healthy red blood cells, and instead creates dysfunctional red blood cells that are not fully developed. The condition worsens over time as the proportion of unhealthy red blood cells rises, but the speed at which this occurs varies between patients. As a result of MDS, about 30 to 40% of people go on to develop acute myeloid leukaemia (AML), which is a form of cancer that affects white blood cells.
Treatment options for patients with MDS generally depend on the severity of the disease, but include blood transfusions, antibiotics, chemotherapy, and pharmaceutical drugs. One type of drug, used to treat particularly aggressive forms of MDS, is called Azacitidine. It works to slow down disease progression and improve healthy blood cell production.
The recent clinical trial by Aprea Theraputics combined their drug APR-246 with the existing drug Azacitdine to treat patients. The patients on the trial all had a certain form of MDS that involved a mutation of the gene TP53 that controls tumour suppression. The TP53 mutation is present in approximately 20% of patients with MDS and 50% of all tumours of any type, and is associated with resistance to drugs used to treat cancer and poorer survival rates. Treating the TP53 mutation is therefore crucial for improving patient prognoses for a range of cancers associated with MDS.
The drug being developed, APR-246, targets the P53 protein produced by the TP53 gene and stimulates it to cause re-activation. This triggers the P53 tumour suppression mechanism, resulting in cancer cell death and patient recovery. This process has been shown to work in several pre-clinical trials, including on blood cancers, ovarian cancer, esophageal cancer, small cell lung cancer, and acute myeloid meukemia. The drug also works well in combination with existing medications.
The drug trial on patients with MDS also announced positive results. All of the eight patients involved in the study showed a response to the drug, and 75% had a complete response and deep molecular remissions. Furthermore, none of the patients so far have relapsed or had serious side effects. The drug hasn’t been found to become toxic with higher dosages, and the maximum safe dosage level has not yet been found.
These are promising results, and further testing of the drug APR-246 is needed to establish the effectiveness and the safety of it in a larger sample of patients. In addition to these outcomes from patients with myelodysplastic syndromes, the drug’s mechanism and pre-clinical studies suggest that its use could be extended to other cancers and disorders as well.
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If you would like to learn more about MDS, check out our partners, the MDS Foundation.
