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Anemia Treatment Has Safety Issues in Mid-Stage Trial

AKB-6548 associated with serious adverse effects

Akebia Therapeutics has reported serious side effects among patients treated with its experimental anemia drug AKB-6548.

AKB-6548 is a once-daily oral therapy in development for the treatment of anemia related to chronic kidney disease (CKD). The drug is designed to stabilize hypoxia-inducible factor (HIF), a transcription factor that regulates the expression of genes involved in the production of red blood cells in response to changes in oxygen levels, by inhibiting the HIF prolyl hydroxylase (HIF-PH) enzyme.

According to Akebia, AKB-6548 exploits the same mechanism of action used by the body to naturally adapt to lower oxygen availability associated with a moderate increase in altitude. At higher altitudes, the body responds to lower oxygen availability with increased production of HIF, which coordinates the interdependent processes of iron mobilization and erythropoietin (EPO) production to increase RBC production and, ultimately, improve oxygen delivery.

In a phase IIb trial, 209 non-dialysis patients with CKD-related anemia were randomly assigned to receive either AKB-6548 or placebo for 20 weeks. At the end of treatment, 54.9% of the patients who received AKB-6548 met the trial’s primary endpoint compared with 10.3% of the placebo group (P < 0.0001). The primary endpoint was defined as achieving or maintaining a mean hemoglobin (Hgb) level of 11.0 g/dL or greater, or as increasing the Hgb level by 1.2 g/dL or more above the pretreatment value, as measured by the mean Hgb value at weeks 19 and 20.

However, a higher incidence of serious adverse events (SAEs) was reported in the AKB-6548 group compared with the placebo group (23.9% vs. 15.3%, respectively), the most common being renal-related. Of the 49 SAEs reported in the AKB-6548 group, one was considered probably related to active treatment and two were considered possibly related, including one death.

AKB-6548 is also being evaluated in a phase II study for the treatment of dialysis patients with anemia related to CKD. Results from that study are expected to be announced in the third quarter of 2015.

Approximately 30 million people in the U.S. have CKD, and an estimated 1.8 million of those individuals also have anemia.

Sources: Akebia Therapeutics; October 27, 2014; and Reuters; October 27, 2014.

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