Respiratory drugs from Novartis ($NVS) and GlaxoSmithKline ($GSK) are top sellers for their companies, with GSK's Advair a longtime megablockbuster. But along with big sales, these drugs show more adverse events in post-marketing safety data than competing products from Merck ($MRK), according to a new report.
Healthcare informatics firm Advera Health Analytics scoured FDA postmarketing safety reports to compile data on side effects for companies producing asthma meds. Advera uses a reporting odds ratio (ROR) to compare the actual number of side effects reported for a certain drug 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 company found that Novartis' Xolair and GlaxoSmithKline's Advair showed more reports of serious side effects than drugs from Merck, including Dulera and Singulair, flagging safety issues ranging from adrenal gland disorders to viral infection.
Xolair turned up the most side effects of all the drugs in the report, with 19 safety signals with RORs over 1.5. The drug, which the FDA slapped with a cardiovascular warning last year, was linked to 390 cases of influenza with an ROR of 8.8; 465 cases of increased blood pressure with an ROR of 4.8; 522 cases of hives with an ROR of 4.8; 754 cases of viral infectious disorders with an ROR of 3.66; and 317 cases of weight gain with a 2.2 ROR.
The numbers came as a bit of a surprise to Advera, which expected the drug to have a "favorable post marketing safety profile" based on medical literature, VP of scientific affairs Keith Hoffman told FiercePharma. But Xolair has a different mechanism of action from the other drugs included in the report, he added, possibly accounting for the increased number of side effects.
"We consider this potential differentiation to be preliminary, however, as an analysis of the patient types [who were] prescribed Xolair, versus other asthma medications, was outside the scope of this investigation," Hoffman said.
Novartis declined to comment about Advera's findings because it is "not familiar with this report and, therefore, unable to comment on its content," a company spokeswoman told FiercePharma in an email. "We work closely with the U.S. Food and Drug Administration to file any adverse event reports according to industry guidelines," she said.Keith Hoffman
Advair also was linked to a number of serious side effects, turning up 12 safety signals with RORs over 1.5. Already dealing with the onslaught of generic competition in Europe, the drug had 112 cases of oral fungal infection with an ROR of 22.4; 794 cases of mouth or throat infections with an ROR of 5.1; 151 cases of glaucoma with an ROR of 4.2; and 373 cases of cataracts with an ROR of 4.1.
But "given that Advair shares a very similar mechanism of action with other members of this asthma drug class" Advera can't make any conclusions about why the drug has more reports of specific side effects than other meds included in the report, Hoffman said.
Merck asthma meds including Singulair and Dulera fared better in Advera's report, showing fewer serious side effects than Novartis and GSK's drugs. Singular turned up 2,114 cases of hypersensitivity with a 2.3 ROR. Dulera had 8 cases of adrenal insufficiency with a 7.1 ROR and 5 cases of growth retardation with a 7.50 ROR. For comparison's sake, Advair was linked to 105 cases of adrenal insufficiency with an ROR of 8.07 and 37 cases of growth retardation with an ROR of 4.79.
"Merck is vigilant in monitoring adverse event reports (AERs) from its clinical trials and post marketing reports, and files regular reports with the FDA and other regulatory agencies for all of Merck's medicines," the company told FiercePharma in an email. The company also pointed to limitations in post-marketing data, saying that reports submitted through the reporting system "often have incomplete medical and drug histories and unsubstantiated diagnoses."
GlaxoSmithKline's blockbuster hopeful Breo Ellipta also generated a fair number of side effects in Advera's report. The drug had 24 cases of rhinorrhea with an ROR of 6.32; 27 cases of palpitations with an ROR of 2.17; 75 cases of pneumonia with an ROR of 2.94; and 13 cases of swollen tongue with an ROR of 4.17.
GSK says Advair and Breo Ellipta "have significantly advanced patient care," the company told FiercePharma in an email. "These medicines have been extensively studied, are used by millions of people worldwide and in the vast majority of people, they are well tolerated," GSK said.
- here's a link to the report (reg. req.)
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