- An experimental anemia pill from Akebia Therapeutics missed a critical safety measure in two large Phase 3 trials, as more patients on Akebia's drug suffered significant cardiovascular events than those on standard biologics. Shares plummeted more than 70%.
- Akebia's treatment however, was just as good as a commonly prescribed biologic at boosting hemoglobin levels in adults with damaged kidneys and not on dialysis. Akebia believes the totality of the data — which include positive results from two other large-scale clinical trials — are still good enough to submit to regulators. The company plans to file the drug, called vadadustat, for approval as early as next year.
- Still, the results leave vadadustat's future unclear, and separates Akebia's drug from other rival pills from FibroGen and GlaxoSmithKline that are now approved in certain countries. The goal for this emerging group of anemia pills has been to show they're just as effective as injectable drugs like Aranesp, but more convenient and potentially safer. Akebia will now have a harder time making that case to regulators.
For years, Akebia has been chasing rival FibroGen in a high-stakes race to try to upend the treatment paradigm for chronic kidney disease patients with anemia.
Both are developing pills meant to trick the body into thinking it's in a low-oxygen environment, stimulating the production of red blood cells and thus boosting hemoglobin levels in people with anemia. And both have steadily produced more and more results showing that they can do so just as well as drugs like Amgen's Epogen and Aranesp, which generate billions of dollars in yearly sales despite being dogged by safety concerns such as the potential to cause heart problems.
FibroGen's drug, roxadustat, has already cleared its Phase 3 tests and is approved in China and Japan, with reviews underway in the U.S. and Europe. Another, similar drug from GlaxoSmithKline just notched its first approval in Japan in June. Another from Bayer is advancing as well.
Akebia hopes to follow suit. It notched victories in two of four planned Phase 3 trials, which tested its drug in thousands of CKD patients on dialysis. But in the other two trials, which enrolled non-dialysis patients and are part of a program called PRO2TECT, the results have not only hurt Akebia's prospects, but might alter FibroGen's as well.
In the PRO2TECT studies, Akebia tested its drug head to head against Aranesp. Regarding safety, researchers tracked how long, from the start of the trial, before patients on either treatment died of any cause or had a heart attack or stroke. Akebia's goal was for vadadustat to prove "non-inferior" to Aranesp. It didn't report specifics, but said that its drug failed to do so, unlike what the company saw in its other two Phase 3 trials.
While Akebia's drug did succeed on its main and secondary goals by matching Aranesp's ability to boost hemoglobin levels, the safety outcome represents a "near-worst case scenario" for vadadustat, wrote RBC Capital Markets analyst Kennen MacKay. It's now unclear whether vadadustat is approvable in "any CKD indication without further study," he wrote. The drug could have commercial problems even if it is, he added.
Akebia still intends to file for approval, however. CEO John Butler, in a statement, cited the "totality of the data" in its Phase 3 program, including analyses in certain geographic regions and patient subgroups in the PRO2TECT trial.
Akebia's prospects aside, Wall Street analysts were mixed as to whether the results could lead to increased regulatory scrutiny of other, similar drugs — FibroGen's among them.
FibroGen's drug was non-inferior to a placebo in a pooled analysis of data from non-dialysis patients, a higher bar given the safety concerns of drugs like Aranesp. Nonetheless, MacKay believes there is now, given Akebia's outcome, "uncertainty as to how the agent might fare versus standard-of-care."
Leerink's Geoffrey Porges, however, disagrees. Citing the "substantial differences in trial designs" between the two drugs, Porges expects roxadustat to be cleared for all CKD anemia patients and to "dominate" the market in the long run.
The non-dialysis dependent market in CKD is worth about $2 to $3 billion, compared to $1 billion for the dialysis-dependent portion, according to Jefferies analyst Michael Yee. FibroGen shares slipped about 4% Tuesday.