FDA Approves New Oral Formulation of Deferasirox

Elliott Vichinsky, MD

The FDA has granted an accelerated approval to an oral film-coated formulation of deferasirox (Jadenu) for the treatment of patients aged 2 and older with chronic iron overload due to multiple blood transfusions, according to an announcement from the drug’s developer, Novartis.

The approval for patients with myelodysplastic syndromes (MDS) was based on the treatment of 627 patients across 5 uncontrolled trials that varied in duration from 1 to 5 years. The primary endpoints for these studies included improvements in liver iron concentration (LIC) and serum ferritin. Following at least 1-year of follow-up, the mean change in serum ferritin level with deferasirox was -332.8 mcg/L (±2615.59) and the mean change in LIC was -5.9 mg Fe/g dw (±8.32).

Deferasirox became the first FDA approved oral therapy for chronic iron overload in 2005. This initial formulation of the drug, labeled Exjade, has to be dissolved in liquid and taken on an empty stomach. The Jadenu formulation can be swallowed whole, offering a convenience advantage for patients.

In addition to transfusion related iron overload, the new oral formulation is indicated for patients 10 years and older with non-transfusion-dependent thalassemia (NTDT). The agent was approved with a Boxed Warning regarding renal failure, hepatic failure, and gastrointestinal hemorrhage.

“Jadenu is an exciting development for patients with chronic iron overload who have been eager for alternative treatment options,” Elliott Vichinsky, MD, director of Hematology and Oncology at the University of California, San Francisco, said in a statement. “Taking iron chelation therapy every day has sometimes been a challenge for them. The administration of Jadenu oral tablets once a day is simple.”

Patients enrolled in the pooled MDS analysis were at varying levels of risk, with 239 participating in studies that limited those with IPSS Low or Intermediate 1 risk MDS. The remaining 388 patients participated in studies that did not require MDS risk stratification. Additionally, the iron chelation therapy is not indicated for patients with high-risk MDS.

In total, 51% of patients completed the planned duration of treatment with deferasirox in the 1-year analysis. In the 3-year study, 52% of patients completed therapy, and 22% of patients completed treatment in the 5-year study. The primary causes of treatment discontinuation included withdrawal of consent, adverse reaction, and death.

Across the 5 studies at 1-year, treatment was discontinued due to adverse events for 20% of patients, 10% withdrew consent, 8% passed away, 4% from other causes, and 3% were due to lab abnormalities. In the 47 patients enrolled in the 5-year study, 10 remained on treatment at the end of study (21.3%).

The most common adverse events in patients taking deferasirox in the MDS pooled analysis were diarrhea (47%), nausea (26%), abdominal pain (23%), creatinine increase (14%), vomiting (13%), and rash (13%).

In total, 393 patients with MDS were over the age of 65 years. These patients experienced a higher frequency of adverse reactions than younger patients, requiring closer monitoring. The recommended starting dose for deferasirox is 14 mg/kg in patients with transfusional iron overload, although the label advises that a lower dose should be used in older patients. For those with renal impairment, the label recommends a half dose.

"Novartis has had a long-term commitment to improving the lives of patients with chronic iron overload," Bruno Strigini, president, Novartis Oncology, said in a statement. “Exjade transformed iron chelation therapy. We responded to feedback from patients and their physicians, and now Jadenu, by simplifying treatment administration, offers an important new option to help meet these patients’ needs."

Both formulations of deferasirox treat chronic iron overload, a side effect associated with blood transfusions that can be fatal if left untreated. In addition to MDS, the treatment is intended for patients with sickle cell disease and other conditions requiring blood transfusion.