Following two FDA rejections of novel oral anemia drugs, all eyes are on GSK’s daprodustat. Now, the drug has come out of an FDA panel meeting partially bruised, losing experts’ support in one of the two patient populations that it’s seeking approval for.
After heated discussions during a Wednesday meeting, an independent FDA adivosry committee voted 11 to 5 that the benefit of GSK’s daprodustat doesn’t outweigh its risk in patients with chronic kidney disease-related anemia who are not on dialysis,
But in a win for GSK, the experts voted 13 to 3 in support of daprodustat’s proposed use in the dialysis-depenent population.
The FDA doesn’t have to follow its advisory committee’s recommendation. If the votes eventually play out in FDA’s decisions, daprodustat could at least partially redeem setbacks previously suffered by two other agents in the novel HIF-PHI oral drug class.
To most experts on the FDA advisory committee, daprodustat’s risks are simply too pronounced to be offset by the administration convenience it offers.The safey signals in the nondialysis-dependent group were more than just the risks of heart failure and bleeding gastric erosions, which were present in the dialysis group.
For nondialysis patients, other risks included heart attack and stroke, among other potential complications. While the experts said they wanted to give patients not on dialysis another treatment option, many were just not satisfied by the data and advised that longer-term studies be conducted with the patient group instead.
It’s a song that’s been heard before, with a bit of a different ending. AstraZeneca and FibroGen’s roxadustat and Akebia Therapeutics’ vadadustat, both also in the same class of oral HIF-PH inhibitors, were previously both shot down by the FDA.
The panel heard from people impacted by chronic kidney disease related anemia, including personal anecdotes of medical emergencies because of lack of treatment options available at home through an oral route. Supporters of daprodustat argued that another treatment option would positively impact their quality of life.
GSK was also questioned about lower-than-expected enrollment of the nondialysis trial in the U.S. In response, GSK said it had anticipated to reach a mark specified by the FDA, but “sometimes you can’t get what you anticipated.” GSK’s answer to the question was largely unclear and was cited by one committee member as a reason she voted no to the benefits in the nondialysis patient population.
When it comes to discussions about daprodustat’s benefits in nondialysis patients, several experts recognized the need for additional treatment options and patient choice in care, especially as existing treatments require that a patient go into a medical center for transfusions, something that many don’t want to risk as COVID-19 is still prevalent.
As for the dialysis-dependent patients, committee member Ravi Thadhani M.D., from Massachusetts General Hospital mentioned that there are many challenges right now in dialysis units, and that an oral medication would prove helpful to lessen the burden.