The U.S. Food and Drug Administration (FDA) in a statement yesterday reported its approval for a new drug, Idhifa (enasidenib) for the treatment of acute myeloid leukemia (AML) in adults that has either relapsed or is refractory to standard chemotherapy.
Patients who are suitable for Idhifa are those with a special genetic mutation. Only they would respond positively to the drug say the research gathered in connection that was submitted to the FDA for the drug’s approval. Along with this drug thus, a companion diagnostic, the RealTime IDH2 Assay would be needed. This assay that would measure specific mutations in the IDH2 gene in AML patients too got approval from the FDA.
According to Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, Idhifa is the tailormade targeted therapy that was being searched for, in patients with AML who had the IDH2 mutation. It “fills and unmet need” he said. He explained that the use of this drug has resulted in complete remission in some patients and also has reduced the need for platelet and red blood cell transfusions in some patients.
Idhifa, the new agent is at the molecular level an isocitrate dehydrogenase-2 inhibitor. This means, it blocks the cell growth by inhibiting several enzymes. Those with IDH2 mutation as detected by the RealTime IDH2 Assay in blood or bone marrow samples, respond well to Idhifa.
A study with 199 patients was cited as the basis for the claims in favour of this drug. There was a single group of 199 patients who had relapsed or refractory AML and who had IDH2 mutations as detected by the RealTime IDH2 Assay. They were treated with Idhifa. At the end of the study the researchers had measured the percentage of patients who had no evidence of the disease left in their body or had a full recovery of their blood counts or were deemed to be on complete remission with partial hematologic recovery from the disease.
Results showed that within six months of therapy with Idhifa;
- 19 percent of patients experienced complete remission for average of 8.2 months
- Complete remission with partial hematologic recovery was seen in 4% patients for an average follow up of 9.6 months
- Of the 199 patients, 157 required blood or platelet transfusions before therapy. Post therapy 34% did not require these transfusions anymore.
Some of the common adverse effects of Idhifa include nausea, vomiting and diarrhoea. Jaundice and rise in levels of bilirubin and loss of appetite was also noted. The drug is not approved for pregnant and breastfeeding women for the potential harm it may cause to the fetus or the baby. Use of Idhifa may also lead to a serious side effect called the differentiation syndrome which leads to fever, difficulty in breathing, fluid around the lungs, inflammation of the lungs, liver and kidney damage, edema or swelling, weight gain and finally damage to most major organs. Differentiation syndrome needs immediate attention and therapy with corticosteroids says the boxed warning on the drug’s label.
The FDA granted orphan drug status to Idhifa to encourage and assist its development. It was given a “Priority review” status due to which the action of approval took place within six month of submission. While Celgene Corporation got the approval for Idhifa, Abbott Laboratories received the approval for the companion diagnostic test RealTime IDH2 Assay. Idhifa would have a monthly list price of $24,872 according to Celgene. The actual price that the patient would pay however would differ based on their individual healthcare insurance plans etc.
Acute Myeloid Leukemia (AML)
AML is a fast progressing cancer of the white blood cells and it begins within the bone marrow and leads to a high rise of abnormal white blood cells in the bloodstream and bone marrow. According to the National Cancer Institute at the National Institutes of Health, by the end of 2017, 21,380 people will be diagnosed with AML and 10,590 patients would succumb to it.
AML is rare before the age of 45 years and typically develops over a few weeks. The symptoms include those of anemia – tiredness, pale skin, shortness of breath and other symptoms such as frequent infections, frequent bleeding from various sites etc. Life threatening bleeding and infections are usually the causes for death in advanced cases.
Treatment is necessary as soon as the diagnosis is conformed as the disease progresses rapidly. Chemotherapy is the mainstay of treatment of AML. Sometimes chemotherapy may be combined with radiation therapy and bone marrow transplant to achieve a remission or cure.
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