Patent Gone, Revenue Gone—But the Molecule Keeps Working
Singulair was one of Merck's best-selling drugs. Then it went generic, and the revenue collapsed like a bone density scan after menopause. In the third quarter of 2012, the asthma pill generated $602 million. The quarter before, it made $1.4 billion. That cliff was the patent expiring in August 2012, and Merck hemorrhaged roughly 55 percent of its Singulair revenue in a single quarter per reporting on Merck's quarterly filing. The molecule, though, did not get the memo.
Montelukast — the generic name — is a leukotriene receptor antagonist, a drug that blocks inflammatory signaling molecules called cysteinyl leukotrienes from latching onto receptors in airway and nasal tissue. It has been prescribed for asthma and allergic rhinitis since the late 1990s. Cheap, well-understood, unremarkable. And now it is quietly becoming one of the more interesting tools in food allergy research.
A small 2014 study at Kansai Medical University in Japan is the origin point. Five children with food allergies undergoing oral immunotherapy — the process of feeding patients gradually increasing doses of an allergen to desensitize their immune systems — hit a wall. Intractable abdominal pain stopped the rush phase in four of them. The researchers gave the children leukotriene receptor antagonists, and the pain subsided. All five completed the protocol and reached their target doses per the case series published in the Annals of Allergy, Asthma & Immunology.
The study is small — five children is not a clinical trial, it is a hypothesis generator — and it has sat in the literature for over a decade. But it found a second audience in November 2025, when Joshua A. Boyce, a researcher at Brigham and Women's Hospital and Harvard Medical School, cited it in a perspective article in the New England Journal of Medicine. Boyce's NEJM piece reviewed evidence that leukotrienes generated in the intestine play a role in food anaphylaxis, the severe systemic allergic reaction that makes food allergies life-threatening. If intestinally produced leukotrienes are part of the problem, blocking them might be part of the solution per Boyce's NEJM perspective.
The proposed mechanism is straightforward enough: oral immunotherapy inflames the gut, which triggers eosinophil activation and mast cell degranulation, both processes driven in part by leukotrienes. Montelukast blocks that inflammatory signal. It does not treat the allergy. It may make the treatment tolerable enough to finish.
This is not the only drug in food allergy right now. Xolair, an anti-IgE antibody, has been studied in the same space — as type0 has reported — and works through an entirely different mechanism. Both drugs are being asked the same question: can they make oral immunotherapy safer or more effective? Two different pathways, converging on the same clinical problem, in the same news cycle. That is the kind of signal biology occasionally throws up when nobody is paying attention to the same old molecule.
Merck's Singulair revenue collapse is a useful reminder of how generics pricing works in pharma. A drug loses patent protection and the innovator stops advertising it, insurers prefer the cheap version, and the brand name becomes a rounding error. Except the molecule is chemically identical. The patent cliff is a CFO story, not a biology story. The global montelukast sodium market is projected by market research firm Mordor Intelligence to grow from $580 million in 2025 to $1.23 billion by 2031 — an estimate, not a clinical forecast, and one that varies across the firm's own pages per Mordor Intelligence's industry report.
The 2014 Japanese study has not been replicated in a larger trial. The NEJM perspective is a review article, not a trial result. Boyce is describing a biological hypothesis that several groups are now working on, not reporting a confirmed therapy. The honest framing is: montelukast is a candidate in food allergy research, supported by mechanistic biology and a small pediatric case series involving five children at a Japanese university. Whether it holds up in controlled studies is an open question.
The question worth asking is whether a thirty-year-old generic can become clinically interesting again through off-label use — and whether that is a business model, a research question, or just a coincidence of biology. Food allergy oral immunotherapy is a brutal treatment. Patients endure years of daily dosing with a substance their immune system is primed to react to, and dropout rates in trials reflect that burden. Anything that makes the process less miserable — if montelukast turns out to do that — would matter to patients even if nobody builds a franchise around it.
Approximately 5.8 percent of children in the United States are diagnosed with a food allergy, totaling roughly 4.2 million children per FARE's April 2024 fact sheet.
Merck's investor relations team is not going to call montelukast a growth platform. The company has moved on. But the molecule is still in the literature, still in the pharmacy, and now — thanks to a Japanese case series and a Harvard perspective piece in NEJM — under review by researchers who think the old asthma drug might have a second act in an entirely different indication.
What happens next is a trial question, not a press release question. Watch clinicaltrials.gov.
† The global montelukast sodium market is projected by market research firm Mordor Intelligence to grow from $580 million in 2025 to $1.23 billion by 2031†
†Source-reported estimate; not independently verified.