AdverseEvents: Analysis of side-effect reports turns up troubling safety signals for Novartis, Eisai drugs

Keith Hoffman

Drugs that treat brain-related diseases are often tied to troubling side effects, with companies listing everything from gambling compulsions and hypersexuality to mood changes and gastrointestinal bleeding on FDA-approved labels. Now an analysis of FDA side-effects reports by healthcare informatics firm AdverseEvents has uncovered more potential safety problems for the meds.

The company sifted the FDA's Adverse Event Reporting System (FAERS) for reports on treatments for Parkinson's disease, epilepsy and Alzheimer's, and applied its own algorithms to identify case reports most likely to be triggered by drug therapy, rather than another cause. The results? Some potentially worrisome signals for two of Novartis' ($NVS) meds, Exelon for Parkinson's and Alzheimer's disease, and Stalevo for Parkinson's disease. The analysis also flagged serious side effects with Eisai's Alzheimer's drug Aricept.

While many of the potential safety issues are tied to a small number of patients, they are still worth looking into, Keith Hoffman, vice president of scientific affairs at AdverseEvents, told FiercePharma. New rounds of data could turn up more and more case reports that need further investigation. The analysis also may confirm suspicions companies already had about a drug, Hoffman said.

As a known example, Hoffman mentioned recent studies that highlighted the risks of compulsive behavior in patients taking certain types of Parkinson's meds. "For this class of drugs, everyone talks about the hypersexuality and that's now clearly demonstrated to be connected with this class of drugs. But there are other things, life-threatening, and this drug class appears more complicated than I originally thought," Hoffman said. "I look at this, and I see the beginning of signals that should be paid attention to."

In this analysis, AdverseEvents flagged reports of cardiopulmonary failure, respiratory failure and death in Exelon and Stalevo patients. The firm said it found 11 cases of cardiopulmonary failure in Exelon patients worth investigating, and 5 cases of acute respiratory failure. Almost 1,200 deaths were reported in Exelon patients, a signal the firm also called worrisome. According to its research, Stalevo was linked to 8 cases of stroke.

Stalevo pills--Courtesy of Maksim, CC BY-SA 2.0

Exelon and Stalevo also had high rates of fracture-related case reports, a safety problem that has not been "widely discussed" with the drugs, Hoffman told FiercePharma. The firm's analysis of Exelon data red-flagged 75 femur fracture reports, 28 upper-limb fracture reports and 32 unspecified fractures. The analysis of Stalevo reports turned up 38 worrisome fracture reports, with 29 hip fractures and 9 lower-limb fractures.

Elderly patients are more likely to fall--and Alzheimer's and Parkinson's patients tend to be elderly. That could have contributed to the fracture numbers, the report notes. But the numbers also suggest a "global weakening of the bones" and are worth watching in the future, Hoffman said. "This certainly looks like the beginning of a signal to me," he said. "People are not diving into this database with the same fidelity that we are. They may see a couple rib fractures but they won't look at broader fractures and see a pattern."

Novartis declined to comment about the numbers because it is not familiar with the AdverseEvents report and therefore unable to comment on its content, spokeswoman Julie Masow told FiercePharma in an emailed statement.

The AdverseEvents report also showed troubling numbers for Eisai's Alzheimer's drug Aricept, with 79 cases of sudden death. AdverseEvents attached a red flag to these numbers because of their high "reporting odds ratio"--a statistical measure of the relative reporting frequency of certain side effects, the firm said. AdverseEvents' analysis also turned up worrisome reports of cardiac arrest, coma and neuroleptic malignant syndrome in Aricept patients. The report cites 113 cases of cardiac arrest, 7 cases of cardiopulmonary failure, 76 cases of coma and 34 cases of neuroleptic malignant syndrome. Eisai declined to comment for FiercePharma.

- here's a link to the report (reg. req.)