Dive Brief:
- The Food and Drug Administration will no longer require a boxed warning about asthma-related deaths on labels of drugs that combine long-acting beta agonists and inhaled corticosteroids, removing a caution that had been in place since 2011.
- A review of four large clinical safety trials conducted by drug companies showed that combining the two types of respiratory drugs did not result in significantly more serious side effect than inhaled steroids alone.
- The studies also examined the efficacy of combining the two types of drugs, and found the pairing was superior than ICS alone at reducing asthma exacerbations. Both the safety and efficacy data from these trials have been added to the combination drug labels.
Dive Insight:
In 2011, the FDA mandated the three big pharma companies manufacturing fixed dose combinations of long-acting beta agonists and inhaled corticosteroids carry out 26-week, randomized, active-controlled clinical safety trials to examine the risk of severe asthma-related events.
Three adult studies compared AstraZeneca plc's Symbicort (budesonide/formoterol) with budesonide alone; GlaxoSmithKline plc's Advair (fluticasone/salmeterol) with fluticasone alone; and Merck & Co's Dulera/Zenhale (mometasone/formoterol) with mometasone alone. A fourth study, in pediatric patients, compared Advair with fluticasone alone.
The four studies included 41,297 patients, and an analysis "showed that LABAs, when used with ICS, did not significantly increase the risk of asthma-related hospitalizations, the need to insert a breathing tube known as intubation, or asthma-related deaths, compared to ICS alone," according to a statement from the FDA.
All three brands are all facing a slowdown or a decline in sales. A flagship brand for AstraZeneca, Symbicort's sales have been ebbed of late, falling 9% during the first nine months of 2017 compared to a year prior. U.S. sales dropped ever faster, down 15% in the same period.
Generic competition for GlaxoSmithKline's Advair looms, and Dulera's sales totaled only $210 in the first nine months of 2017, compared with $331 million over the same period the previous year.
While the removal of the warning is unlikely to reverse that market erosion, it should give physicians and patients more confidence in the long-term safety of the combinations.