According to a new report that looked at emerging safety risks linked to the flu drug Xofluza and three migraine medications, Aimovig, Ajovy and Emgality, federal regulators may not have required robust enough clinical trials before approving the medications for use on the public.
The Institute for Safe Medication Practices (ISMP) issued a QuarterWatch report last week, which indicates that the U.S. Food and Drug Administration (FDA) should have required more in-depth clinical trials on a number of new medications, instead of leaving their safety profiles up to post-marketing surveillance, which some critics say uses the public as guinea pigs.
One of those drugs was Xofluxa (baloxavir marboxil), approved by the FDA in October 2018. It is the first new antiviral treatment for influenza in almost 20 years, and is marketed by Genentech. However, the report notes that the FDA approved Xofluxa after it had been tested on only 710 patients.
The third, and most crucial phase of testing only involved 113 patients in North America, of which only 18 were African Americans and only 32 were Hispanics. The racial differences may be important, because there is evidence that the benefits differed between Japanese and North American test subjects.
Since the drug was approved, there have been at least 50 cases of potentially life-threatening allergic reactions reported to the FDA’s adverse event reporting system (FAERS), including three deaths. There have also been reports of central nervous system problems, and gastrointestinal complications. Most of the reports came from Japan, where use was more widespread.
“Given that potentially millions of people might be exposed to a new flu treatment, the limited clinical testing for FDA approval left questions unanswered about both benefits and risks,” ISMP researchers warned.
ISMP researchers reached out to Genentech, which confirmed it has seen a safety signal for hypersensitivity, including anaphylactic shock, and is currently monitoring the reports.
Benefits of New Migraine Drug Class Highly Variable
The ISMP also looked at an entirely new class of migraine biological medications, including Aimovig (erenumab-aooe), by Amgen, approved in May 2018; Ajovy (fremanezumab-vfrm), by Teva Pharmaceuticals, approved in September 2018, and Emgality (galcanezumab-gnlm), by Eli Lilly, which was also approved in September 2018. All of the drugs block the effects of a signaling molecule believed to play a role in migraines.
“One striking feature of these new products was large variability in their effects. The results ranged from no effect in some patients in reducing migraine days, to others who reported treatment eliminated–or nearly eliminated–migraine headaches,” the researchers wrote. “The early adverse event data showed that erenumab-aooe also had adverse effects, some apparently underestimated in its clinical studies.”
On the benefits side of things, the ISMP report notes that even the clinical trials showed a substantial placebo effect, meaning patients who received a fake pill reported fewer migraines, even though they were not actually given any medications.
However, adverse event reports included constipation, sometimes up to the point of hospitalization, as well as hair loss, injection site reactions and rare cases of anaphylactic shock.
“The most striking feature of the (Aimovig) adverse event data was the sheer number of case reports in our totals for the 12 months ending with 2019 Q1. We identified 10,508 case reports, including 1,458 with a serious outcome,” the report warns. The drug ranked first in number of reports for 33 new drugs approved in 2018 and accounted for more than twice as many cases as the other 32 new drugs combined.”