Alzheimer's drug development is a difficult venture, as pharma knows all too well. The meds' troubling side effects and potential safety issues make marketing a risky game, with few companies grabbing a seat at the table. According to a recent analysis of postmarketing data, meds from Novartis ($NVS), Allergan ($AGN) and Japan's Eisai turned up more reports of potentially dangerous side effects than other products.
Healthcare informatics company Advera Health Analytics delved into FDA postmarketing safety reports and compiled data on Alzheimer's drugs from different companies using a reporting odds ratio (ROR), which compares the actual number of side effects reported for a particular med with how many are expected. An ROR above 1.5 indicates a potential safety issue or at the very least something to keep an eye on.
The firm found that Novartis' Exelon patch, Allergan's Namenda and Eisai's Aricept showed more reports of serious side effects than other drugs, with safety issues ranging from convulsions and gastrointestinal hemorrhage to respiratory failure and sudden death.
Exelon was linked to the most troubling side effects, including 20 safety signals with RORs over 2.0. In particular, the drug turned up 309 cases of agitation with an ROR of 5.83, 221 cases of abnormal behavior with an ROR of 6.72, and 335 cases of hallucination with an ROR of 8.68.Advera VP of Scientific Affairs Keith Hoffman
The med was also tied to 23 cases of femoral neck fracture with an ROR of 8.25 and 44 cases of fracture with an ROR of 5.92. But those side effects could be related to the fact that Exelon is prescribed for Parkinson's patients, who are more likely to fall, Advera Health Analytics VP of scientific affairs Keith Hoffman told FiercePharma.
A Novartis spokeswoman said in defense of Exelon's record in Alzheimer's patients that some symptoms such as hallucinations, agitation, fractures and abnormal behavior "may also be related to the underlying disease in this population." She told FiercePharma in an email: "Patient safety is of paramount importance for Novartis and we monitor all aspects of patient safety on an ongoing basis." She added that Novartis "thoroughly evaluates all signals" from postmarketing data to see if they result in adverse drug reactions.
Namenda was also linked to a number of adverse events, including 274 reports of agitation with an ROR of 8.90, 144 reports of abnormal behavior with an ROR of 7.40, 147 reports of hallucination with an ROR of 6.35, 95 reports of hypersomnia with an ROR of 12.87, and 11 reports of femoral neck fracture with an ROR of 6.64.
Aricept had 197 cases of agitation with an ROR of 6.33, 86 cases of abnormal behavior with an ROR of 4.39, 123 cases of hallucination with an ROR of 5.31 and 313 cases of syncope, or loss of consciousness, with an ROR of 8.19.
All three drugs showed elevated RORs for side effects including decreased and nonspecific blood pressure disorders and shock, eating disorders and disturbances and movement disorders including Parkinson's. Aricept, for example, had 663 cases of blood pressure disorders and shock with an ROR of 2.34. And Exelon had 234 cases of eating disorders with an ROR of 5.36.
Eisai declined to comment on Advera's findings for Aricept. The company told FiercePharma in an email that it "has not had the opportunity to review the full report published … or the algorithms that were used for the firm's analysis." But Eisai "stands behind the safety and efficacy of Aricept," it added, noting that it "actively monitors the safety profile of its products through a variety of methods, including the collection and review of spontaneous reports, monitoring of the literature, and analysis of clinical trial data."
Advera also looked at Johnson & Johnson's ($JNJ) Razadyne and Razadyne ER and Allergan's Alzheimer's newcomer Namzaric. Razadyne and Razadyne ER showed fewer reports of serious side effects than the aforementioned drugs, but it is still too early to analyze postmarketing data for Namzaric, the company said in its report.
It's difficult to state conclusively why Razadyne and Razadyne ER turned up fewer adverse events than Aricept, Exelon and Namenda, Hoffman said. Except for Namenda, the drugs work similarly. And even with a drug class in which most of the meds work the same way, there can be "widely varying safety conjecture" in the medical literature, Hoffman said.
"We look at the literature and say, okay, there's speculation about these types of side effects. Is there evidence to support such in the real world post-marketing data we have access to? And we'll look at those data and sometimes the safety issue mentioned in the literature correlates, but sometimes it does not," Hoffman said. "Usually we could postulate that mechanistic differences between Razadyne and other drugs in the class might explain the varied post-marketing results we saw here. In this case however, we cannot make that assumption as the drugs work in the same way."
J&J's Janssen division said in an email to FiercePharma about the safety of Razadyne and Razadyne ER that "our highest priorities are the safety and well-being of patients who use our products. We continually monitor the safety of all Janssen medicines and report adverse events to the FDA and other regulatory authorities, as required and necessary."
- here's a link to the Advera Health Analytics report (reg. req.)