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 advisory committee voted 11-5 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 13-3 in support of daprodustat's proposed use in the dialysis-dependent population.
The FDA doesn't have to follow its advisory committee's recommendation. If the votes eventually play out according to the 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 safety 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, 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 choices in care, especially as existing treatments require that a patient go into a medical center for transfusions, something 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 there are many challenges right now in dialysis units, and an oral medication would prove helpful to lessen the burden.
Upon discussing the risks in the patient group, the panel had a lot to say. One panel member, Kevin Abbott, M.D., from the National Institute of Diabetes and Digestive and Kidney Diseases, pointed out the short time frame of the studies, arguing that the safety risks might become a bigger problem over time. Again, several experts suggested that longer-term studies would be helpful, especially one in which daprodustat is compared to a placebo.
Some panel members stressed that the safety risks should be taken seriously because daprodustat showed those problems compared with existing erythropoietin-stimulating agents, which are already known to carry heart safety risks. The five members who voted yes did so because of the lack of treatment options for the patient group, as well as a desire to “not stick with the status quo,” one member stated.
While the benefits were less for the dialysis population, most panel members voted yes because they saw the data in this group as more assuring than the other and were more comfortable with the benefits and risks.
Chris Corsico, GSK's senior vice president of development, said in a statement shortly after the adcomm that the company is “pleased” with the result.
“Today’s robust discussion was an important step in the review of daprodustat. We are pleased the committee recognised the potential for daprodustat to help certain patients who are living with anaemia of CKD given limited treatment options," Corisico said, adding that GSK looks forward to continued work with the FDA as daprodustat's NDA is reviewed.