Ferriprox Safe, Effective Over Long Term at Lowering Patients’ Iron Load

3-year trial data supports use with SCD to counter buildup due to transfusions

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Ferriprox | Sickle Cell Anemia News | Ferriprox in long-term use | clinical trial illustration

Long-term treatment with Ferriprox (deferiprone) safely and effectively reduced iron load in children and adults with blood transfusion-induced iron overload due to sickle cell disease (SCD) or other anemias.

That is according to three years of data from a one-year Phase 4 clinical trial, called FIRST (NCT02041299), and its two-year extension study, FIRST-EXT (NCT02443545), which previously supported the therapy’s approvals for these indications.

Results were detailed in the study, “Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years,” published in the journal Blood Advances.

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People with SCD produce a defective form of hemoglobin, the protein in red blood cells that transports oxygen. This so-called sickle hemoglobin impairs oxygen transport throughout the body and increases blood viscosity (thickness and stickiness), leading to pain crises and organ damage.

To ease anemia and lower blood viscosity, SCD patients often receive blood transfusions. However, since “the body has no natural mechanism to eliminate excess iron,” the researchers wrote, transfusions can lead to a condition known as iron overload, which may damage internal organs.

Ferriprox, an iron-chelating therapy, tested for SCD in Phase 4 trials

Iron-chelating therapies are agents that bind to iron and dampen its reactivity by helping the body eliminate it, mainly through urine. For this reason, these medicines are a common option for SCD patients receiving blood transfusions.

Originally developed by ApoPharma and acquired by Chiesi Global Rare Diseases in 2020, Ferriprox is a lab-made, orally available iron-chelating agent that reduces iron levels by entering cells and removing toxic iron from organ tissues and fluids.

The therapy was originally approved for adults and children, ages 3 and older, with thalassemia — another inherited blood disorder commonly managed with blood transfusions — when current iron-chelating treatment was ineffective.

Last year, this indication was expanded in the U.S., Brazil, and Canada to also cover those with transfusion-induced iron overload due to SCD and other anemias. These label expansions were supported by positive data from the international, open-label Phase 4 FIRST trial and its extension study FIRST-EXT.

FIRST evaluated Ferriprox’s one-year safety and effectiveness against Desferal (deferoxamine mesylate), Novartis’ iron-chelating agent, in 230 people, ages 2 and older, with iron overload associated with SCD and other transfusion-dependent anemias.

Ferriprox was taken daily, at a weight-based dosage divided into three equal doses, taken about eight hours apart. Desferal was administered through an under-the-skin infusion over eight to 12 hours, five to seven days a week.

Results, announced by Chiesi in May 2021 and published early this year, showed that Ferriprox was not inferior to Desferal at reducing iron levels in the liver.

After completing FIRST, participants were invited to enroll in its extension study, in which all received Ferriprox for up to two years (totaling up to three years of treatment) to assess the therapy’s long-term safety, tolerability, and effectiveness.

“Both the FIRST and FIRST-EXT studies were terminated prior to their planned completion based on recommendation of the Data Safety Monitoring Board on the basis that sufficient data had been obtained and that existing methods of surveillance for deferiprone safety were adequately informative,” the researchers wrote.

Newly published data concerned findings of the FIRST-EXT study. Of the 164 patients who completed the FIRST trial, 134 (81 males and 53 females) entered FIRST-EXT: 89 who had received Ferriprox and 45 who had received Desferal.

Extension study finds significant drop in total body iron load over time

Their mean age was 16.2 years (range, 4–47 years) and most had a diagnosis of SCD (85.8%) and were enrolled at study sites in Egypt (81.3%). Patients received Ferriprox for a mean of 2.1 years over the two studies, with most (91%) being on the therapy for at least one year and 41.8% receiving it for at least 2.5 years.

Results showed that Ferriprox’s longer-term safety profile was consistent with that reported in the FIRST trial and other studies in thalassemia patients. Most adverse events were mild in severity, and no new safety concerns were identified.

The most common adverse events considered at least possibly related to Ferriprox in FIRST-EXT included neutropenia, or low levels of a type of immune cell called neutrophils (9%), and abdominal pain (7.5%).

Two patients (1.5%), both with SCD, withdrew from the study due to adverse events: lower neutrophil and platelet counts in one patient — who was on other medications known to increase the risk of these events — and generalized swelling in the other.

Liver iron concentration (LIC), the major indicator of total body iron load, progressively and significantly fell over time relative to study’s start (baseline), including in patients who switched from Desferal to Ferriprox in the extension study.

A gradual drop in mean levels of ferritin, the main iron-storage protein, was also observed, with reductions reaching statistical significance in the first and second year of FIRST-EXT relative to baseline.

The proportion of responders in terms of LIC and ferritin — those showing at least a 20% drop from baseline — also increased each year: from 46.5% to 66.1% for LIC-based responses and from 35.2% to 70.9% for ferritin-based responses.

Iron levels in the heart were within the normal range at the study’s start and remained unchanged during the extension study.

Notably, these findings were true for both SCD patients and those with other anemias.

These results highlight that “long-term therapy with [Ferriprox] was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias,” the researchers wrote.

As such, Ferriprox “offers an additional oral iron chelation option for long-term use in patients with SCD and other anemias,” they wrote.

“Full adherence to chelation therapy is essential to optimize long-term patient outcomes,” the team added, and real-world adherence to Ferriprox has been reported to be generally lower than in clinical trials due to “the inconvenient midday dose.”

A twice-a-day modified-release formulation is also available in the U.S. for transfusion-induced iron overload due to thalassemia, SCD, or other anemias. This formulation “may further improve real-world patient adherence and subsequently improve efficacy outcomes for patients with SCD prescribed [Ferriprox],” the researchers wrote.