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:

  1. 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.
  2. 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.
  3. 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.”

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

CSL CEO Paul McKenzie (L) and CMO Bill Mezzanotte

Q&A: New­ly-mint­ed CSL chief ex­ec­u­tive Paul McKen­zie and chief med­ical of­fi­cer Bill Mez­zan­otte

Paul McKenzie took over as CEO of Australian pharma giant CSL this month, following in the footsteps of long-time CSL vet Paul Perreault.

With an eye on mRNA, and quickly commercializing its new, $3.5 million-per-shot gene therapy for hemophilia B, McKenzie and chief medical officer Bill Mezzanotte answered some questions from Endpoints News this afternoon about where McKenzie is going to take the company and what advances may be coming to market from CSL’s pipeline. Below is a lightly edited transcript.

Boehringer re­ports ro­bust sales led by type 2 di­a­betes and pul­monary drugs, promis­es more to come high­light­ing obe­si­ty

Boehringer Ingelheim reported human pharma sales of €18.5 billion on Wednesday, led by type 2 diabetes and heart failure drug Jardiance and pulmonary fibrosis med Ofev. Jardiance sales reached €5.8 billion, growing 39% year over year, while Ofev took in €3.2 billion, notching its own 20.6% annual jump.

However, Boehringer is also looking ahead with its pipeline, estimating “In the next seven years the company expects about 20 regulatory approvals in human pharma.”

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

FDA ap­proves Nar­can opi­oid over­dose re­ver­sal spray for over-the-counter sale

The FDA today approved Emergent BioSolutions’ Narcan brand naloxone nasal spray for over-the-counter sales. The nod was expected and comes on the heels of a unanimous 19-0 advisory committee vote in favor of approval last month.

The move to OTC means the opioid overdose reversal agent will now be available on grocery, convenience and gas stations shelves, as well as potentially for purchase online.

J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Sally Susman, Pfizer EVP and chief corporate affairs officer

Q&A: Pfiz­er cor­po­rate com­mu­ni­ca­tions chief Sal­ly Sus­man dis­cuss­es book craft­ed in pan­dem­ic and per­son­al lessons

From the political arena to the finance and beauty industries to pharmaceuticals, Pfizer’s Sally Susman has broken barriers, stereotypes and conventions. And now the chief communicator is “Breaking Through,” the title of her first book about effective and innovative communications launching today. The full official title is “Breaking Through: Communicating to Open Minds, Move Hearts, and Change the World.”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.