Where are all the generic inhalers for asthma and COPD? Researchers call for patent and FDA reforms
Take a look at the 53 inhalers approved by the FDA to treat asthma and COPD from 1986 to 2020, and you will find generic versions for just four of those brand-name products, and a widening gap where manufacturers may be hesitant to jump in, researchers from Georgetown, the University of Calgary, University of West Virginia and Harvard wrote in a Health Affairs article published yesterday.
That dearth of competition has meant decades of monopolies for blockbuster inhalers dispensing common asthma, COPD and other treatments like albuterol, budesonide formoterol, and fluticasone-salmeterol. But there has been a slight uptick in progress recently as they note:
The market entry of generic inhalers for three brand-name reference products, all within the past three years, has certainly expanded access to therapy for patients with asthma and COPD in the US. However, these new generic products cover only two therapeutic classes; brand-name inhalers in the majority of classes face no direct generic competition.
So why the lack of competition and what to do about it?
Sanjay Reddy of Georgetown University, Reed Beall of the University of Calgary, S. Sean Tu of the University of West Virginia, and Harvard’s Aaron Kesselheim and William Feldman point to three main reasons for the generic struggles:
- The market isn’t that lucrative for many of the inhalers, with the authors noting that some products had US sales consistently below $100 million annually.
- The high regulatory bar set by the FDA for approving generic drug-device combo products. The researchers note the example of GSK’s Advair Diskus (fluticasone-salmeterol), which went off patent in 2016, but the FDA rejected three of the first generic applications from Mylan, Hikma, and Sandoz before approving a generic in 2019.
- Patent thickets around inhalers, which “may be sidelining generic manufacturers because the risks of unsuccessful paragraph IV challenges may be too great,” they wrote.
And while some of the generics may not be profitable, others will be. Feldman told Endpoints News via email, “The vast majority of brand-name inhalers have no independent generic competition. These include some of the biggest selling products, including GSK’s Trelegy Ellipta and Breo Ellipta, Boehringer Ingelheim’s Spiriva, and AstraZeneca’s Symbicort.”
Trelegy Ellipta hauled in more than $2 billion for GSK last year, while Breo Ellipta brought the UK company more than $1.3 billion in sales, according to earnings reports. Boehringer’s Spiriva brought in more than $1.5 billion in 2022, while Symbicort, which does have a generic version approved but not yet marketed, saw more than $2.5 billion in sales.
As far as ways to alleviate these pressures on generic firms, the authors argued that Congress could enhance the incentives around generic drug-device combo product development via increased exclusivity for successful paragraph IV certifications “from 180 days to a year or more” and “similar exclusivities for successful inter partes review challenges.”
To get those generics in place, Congress also could shorten the automatic thirty-month exclusivity for brand-name combo products that litigates paragraph IV challenges, the researchers argue, while the FDA could allow patents to be added to existing Orange Book listings “only if they could be linked to meaningful clinical benefit.”
But they also note that patent-related reforms may not be enough, given the high upfront and manufacturing costs, and the FDA may have to do more on its end to get generics across the finish line faster, even as bioequivalence is more difficult to demonstrate with these combo products than with oral drugs, and user error “is a greater concern.”
“The FDA should continue refining the process by which generic drug device combinations are approved while maintaining high standards for bioequivalence,” they write, noting that the agency has already made “considerable investments in research to facilitate demonstrations of bioequivalence for inhaled products, and it has released product-specific guidance for several brand-name inhalers.”