Akebia's anemia drug faces further setback after just missing in a COVID-19 trial

Akebia’s ambitions for its drug vadadustat has gotten knocked back once again. Less than five months after the FDA dashed the biotech's hopes to market the med for anemia, the therapy has failed to scrape through in a trial of COVID-19 patients with acute respiratory distress syndrome (ARDS).

The phase 2 trial of 449 adults assessed the effects of a 900 mg daily oral dose of the drug given to hospitalized patients for up to 14 days compared to placebo. While the study showed that a smaller proportion of patients in the dosed cohort went on to require oxygen therapy, needed ventilation or died, the trial failed to meet its primary superiority threshold of a more than 95% probability of benefit.

However, the drug came very close, demonstrating a 94% probability of benefit at day 14 according to these same scores, the company pointed out. At day 14, a total of 13.3% of patients in the vadadustat cohort had reached a 6, 7 or 8 on the combined scale, compared to 16.9% on placebo.

Perhaps unsurprisingly for patients hospitalized with COVID-19, the rate of treatment-emergent adverse events was high for both the vadadustat and placebo groups—at 78.6% and 76.2%, respectively. The incidence of serious treatment-emergent adverse events was 27.9% in the vadadustat group and 32.7% in the placebo group, with the most serious of these being COVID-19 pneumonia—affecting 19.5% and 27.4%, respectively— and septic shock, which affected around 11% of each group.

Despite the narrow miss, Akebia CEO John Butler remains upbeat about the drug’s potential. “While the trial missed its prespecified primary endpoint at day 14, we are extremely encouraged by the data and believe they support further developing vadadustat as a treatment for ARDS due to COVID-19 or other causes,” Butler said in a press release Thursday. “We will now work to review the full data set more thoroughly, consult with experts in the field and ultimately consult FDA on a potential path forward.”

The kidney disease-focused biotech could certainly do with some good news for vadadustat, which is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. The FDA issued a complete response letter in March halting trials of the drug in anemia, citing concerns about the rate of major adverse cardiovascular events in non-dialysis patients, the increased risk of thromboembolic events and cases of drug-induced liver injury. In the wake of the rejection, Akebia’s partner Otsuka Pharmaceutical cut its ties with the drug.

Vadadustat is approved in Japan to treat anemia due to chronic kidney disease and is under review by the European Medicines Agency for a similar indication.