William Feldman

Independent Article Patent Thickets and Product Hops: Challenges and Opportunities for Legislative Reform William B. Feldman Brigham and Women’s Hospital and Harvard Medical School Abstract Two key strategies that brand-name pharmaceutical manufacturers employ to limit generic competition are patent thickets and product hops. The former strategy entails obtaining numerous patents on peripheral features of products (not just the active ingredients), and the latter involves shifting active ingredients into reformulations with new patent protection that can extend periods of market exclusivity. These strategies have become particularly problematic for drug-device combinations like inhalers and glucagon-like peptide-1 receptor agonists, which contain pharmaceutical compounds that are sold together with their delivery devices. The Senate Judiciary Committee moved three bipartisan bills out of committee during the last legislative session aimed at facilitating more timely generic competition. Although these bills offer a valuable step forward, more is needed to limit the sort of patent gamesmanship that has become pervasive in the US pharmaceutical industry. Such reforms should include routine reexamination by the US Patent and Trademark Office of patents submitted for listing with the Food and Drug Administration (FDA), a greater role for the FDA in reviewing such listings, limits on the number of patents that brand-name firms can assert when suing for infringement following patent challenges, stronger incentives for patent challenges, and more flexibility for the FDA to approve complex generic drugs. Keywords: patent thickets; product hops; inhaler; GLP-1 receptor agonist; Food and Drug Administration

New on FirstView: "Patent Thickets and Product Hops: Challenges and Opportunities for Legislative Reform" by @wbfeldman.bsky.social explains the strategies pharmaceutical manufacturers use to limit generic competition — and how to overcome them. #GenericDrugs

www.cambridge.org/core/journal...

So, even if you are unwilling to trade environmental benefit for cost, which I definitely get, the choice will not even exist in these types of cases, which is all very frustrating!

So there will only be the expensive version of Breztri (with longer patent protection and slower generic competition).

And this will be bad for patients, much like the CFC-to-HFA transition.

Breztri is a good example. Will likely be the first MDI with a novel propellant in the US. AstraZeneca will pull the older version once the newer one is released for financial rather than regulatory reasons (with no ban on the horizon).

I hear you. I think keeping prices down is absolutely a priority--and sadly not where we are headed. The switch to novel propellants will be so lucrative for manufacturers and, in a some cases, there will be no lower-cost version that remains on the market.

Key message here is that there is actually little conflict between good care and the environment. The most effective asthma care is also best for the environment.
-reduces the need to use reliever medication
-reduces the number of acute exacerbations
www.nice.org.uk/news/article... #RespEd #LungSky

Thanks as ever to Gregg Furie for his work and collaboration on these issues.

But one thing is clear: Only structural reform, and not individual decisions by even committed physicians, can ensure that patients with chronic respiratory disease have access to safe, effective, sustainable, and affordable therapy.

There are no easy answers here. We discuss some policy solutions in the piece.

...Loss of product exclusivity through patent expiration currently poses a much greater risk to revenue than climate related risks.” As with the last propellant transition, patients may be caught in the middle.

Here’s how AsraZeneca described the financial upside it sees: “Transitioning to new low GWP propellants as part of our Ambition Zero Carbon strategy will mitigate the financial risks posed to our MDI-based respiratory portfolio (e.g. Symbicort)…

New low carbon-inhalers are now under development, but these will be expensive and may be on-patent into the 2030s/2040s. Manufacturers earned billions from the last propellant transition (CFCs to HFAs) and could earn even more during this next round.

Many also have links to the tobacco industry; Phillip Morris International purchased an inhaler manufacturer in 2020 despite uproar by physicians.

Metered-dose inhalers are potent greenhouse gas emitters. Dry powder inhalers are better for the environment but are not suitable for all patients and not always available on formularies.

The Moral Injury of Inhaler Prescribing | NEJM Many inhalers that are vital for patients with asthma or COPD are associated with societal harms that can worsen the very diseases the products are designed to treat. How can this dilemma be resolved?

Our latest in @nejm.org on the dilemmas of treating patients with chronic lung disease.

www.nejm.org/doi/full/10....

Association Between Industry Payments and Prescription of Inhaled Medications - PubMed Association Between Industry Payments and Prescription of Inhaled Medications

Physicians who receive money from inhaler manufacturers prescribe more inhalers in the future. New findings from Hasan Nadeem, @wbfeldman.bsky.social &co:

pubmed.ncbi.nlm.nih.gov/39937634/

Man dies of asthma attack after inhaler cost skyrockets to more than $500 United Health Group’s pharmacy benefit manager, Optum Rx, stopped covering Cole Schmidtknecht’s ‘life-changing’ inhaler, suit alleges.

United Health Group’s pharmacy benefit manager, Optum Rx, stopped covering Cole Schmidtknecht’s “life-changing” inhaler, suit alleges.

Glucose-Lowering Medications and Risk of Chronic Obstructive Pulmonary Disease Exacerbations in Patients With Type 2 Diabetes, JAMA Internal Medicine.

🔎 New in JAMA IM: Avik Ray, @wbfeldman.bsky.social & colleagues assess the comparative effectiveness of diabetes drugs in COPD patients.

They find GLP-1s & SGLT-2s are associated with lower risks of moderate or severe COPD exacerbations vs. DPP-4s during follow-up: jamanetwork.com/journals/jam...

Democrats can win back some of the public’s trust by building an agenda around game-changing ideas *if* they address systemic issues like patent abuse at their root, rather than continuing to settle for legislation that is watered down and incremental at best. 1/8

🔗 www.nytimes.com/2025/02/01/o...

🚨 Just out today (online)! 🚨

Our results show that a common argument against #QALYs (based on the use of subgroup analyses) is not justified with empirical data.

With co-authors: @leah-rand.bsky.social , @wbfeldman.bsky.social, & @akesselheim.bsky.social from @portalresearch.org.

Triple inhalers in COPD: no outcome disadvantage with low-carbon option, study suggests Patients using a triple combination dry powder inhaler had a slightly lower rate of COPD exacerbations than those using a high-carbon metered-dose inhaler, a retrospective study has found.

Treating COPD with DPI triple therapy had slightly lower exacerbation rates than with MDI triple therapy (about 7-9% lower). Better for patients, better for planet!
Mimms write up www.mims.co.uk/triple-inhal... and BMJ paper www.bmj.com/content/387/...

Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study Objective To compare the effectiveness and safety of budesonide-glycopyrrolate-formoterol, a twice daily metered dose inhaler, and fluticasone-umeclidinium-vilanterol, a once daily dry powder inhaler,...

Dry powder inhaler shows similar effectiveness and safety to metered-dose inhaler, w numerous implications including that environmentally-friendly prescribing in this case is also clinically equivalent -- led by @wbfeldman.bsky.social of @portalresearch.org in BMJ: www.bmj.com/content/387/...

Great to work on this piece with Samy Suissa, @akesselheim.bsky.social. Jerry Avorn, Max Russo, Sebastian Schneeweiss, and Shirley Wang. @portalresearch.org

Particularly given the added climate impact of metered-dose inhalers, health systems designing formularies and setting treatment guidelines may consider steps to increase use of fluticasone-umeclidinium-vilanterol relative to budesonide-glycopyrrolate-formoterol.

We found that budesonide-glycopyrrolate-formoterol was associated with a slightly higher incidence of moderate or severe COPD exacerbations compared to fluticasone-umeclidinium-vilanterol in patients with COPD treated in routine clinical care.

There are two single-inhaler triple therapies available in the US: one a metered-dose inhaler (budesonide-glycopyrrolate-formoterol, Breztri Aerosphere) and the other a dry powder inhaler (fluticasone-umeclidinium-vilanterol, Trelegy Ellipta).

A Hidden Contributor to Climate Change — Asthma Inhalers The U.S. health care system could reduce emissions from asthma inhalers and mitigate their negative impact on population health.

By way of background: Metered-dose inhalers are associated with 20-times the greenhouse gas emissions as dry powder inhalers--with emissions in the US equivalent to roughly 550,000 cars on the road each year.

www.commonwealthfund.org/blog/2023/hi...

Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study Objective To compare the effectiveness and safety of budesonide-glycopyrrolate-formoterol, a twice daily metered dose inhaler, and fluticasone-umeclidinium-vilanterol, a once daily dry powder inhaler,...

I'm excited to share a new study out today in @bmj.com comparing the two single-inhaler triple therapies on the US market.

Brief thread below!

www.bmj.com/content/387/...

Pre-holiday PPV: Fed Circuit in Teva v Amneal follows recommendation in amicus brief written by @wbfeldman.bsky.social and Sean Tu of @portalresearch.org, affirming delisting of improper inhaler patents from OB and helping promote timely generic competition: fedcircuitblog.com/wp-content/u...