Allergy and immunology saw significant regulatory momentum in the first half of 2026, headlined by new approvals in allergic fungal rhinosinusitis (AFRS), pediatric hereditary angioedema (HAE), and epinephrine access, alongside pipeline advances in systemic mastocytosis and HAE. Updated international guidelines further refined first-line treatment strategies for pediatric HAE and epinephrine use in anaphylaxis.
HCPLive rounds up the key FDA decisions, trial data, and guideline updates clinicians need to know from the year so far.
Allergy First Half Recap 2026: At a Glance
- Dupilumab (Dupixent): First therapy approved for allergic fungal rhinosinusitis (AFRS)
- Berotralstat (Orladeyo): First once-daily oral HAE prophylaxis for ages 2-11
- Neffy: Age restriction removed; now weight-based (≥33 lbs)
- Bezuclastinib: NDA accepted for non-advanced systemic mastocytosis; PDUFA date: December 30, 2026
- BW-20805: Fast Track designation granted for HAE (siRNA, targets prekallikrein)
- Sebetralstat (Ekterly): named first-line on-demand therapy for pediatric HAE (ages ≥12)
- New international consensus clarifies when to administer epinephrine for anaphylaxis
FDA Approvals in Allergy
The FDA approved dupilumab (Dupixent) for AFRS in patients aged ≥ 6 years with a history of sinonasal surgery, marking the first therapy specifically indicated for this type 2 inflammatory CRS subtype. Approval was based on the phase 3 LIBERTY-AFRS-AIMS trial (n = 62).
At week 52, dupilumab produced a 50% improvement in Lund-Mackay CT opacification scores versus 10% with placebo. Systemic corticosteroid use and surgery risk dropped 92% relative to placebo, with nasal congestion, polyp scores, and anosmia also improving significantly.
The FDA approved berotralstat (Orladeyo) oral pellets for long-term prophylaxis of HAE in children aged 2 to 11 years, making it the first once-daily oral option for this age group. The pellets can be sprinkled onto non-acidic food, offering an alternative to injectable therapies like lanadelumab.
Approval was based on the APeX-P trial, which showed sustained reductions in HAE attack rates, with mean monthly attacks reduced to 0. More than half of patients remained attack-free for up to 1 year. No cardiovascular safety signals were observed across age, sex, or severity subgroups.
Other FDA updates: Neffy Label Update, NDA Accepted, & More
The FDA eliminated the minimum age requirement for 1 mg epinephrine nasal spray (neffy), shifting eligibility to weight-based criteria for patients ≥ 33 lbs, regardless of age. ARS Pharmaceuticals announced the labeling update on March 27, 2026, aligning nasal spray dosing with existing epinephrine auto-injector weight thresholds.
Nicole Chase, MD, noted the update reflects longstanding clinical practice of giving epinephrine to lower-weight children. The label also addresses storage flexibility, tolerating brief temperature extremes, and clarifies dosing technique to avoid inadvertent sniffing during administration, which has been linked to most reported adverse effects.
Related: Weight-Based Dosing Informs Age Removal for Epinephrine Nasal Spray, With Nicole Chase, MD
FDA Removes Age Requirement for Epinephrine Nasal Spray, Now Based on Weight Alone
The FDA accepted Cogent Biosciences' NDA for bezuclastinib in non-advanced systemic mastocytosis, setting a PDUFA date of December 30, 2026. The oral KIT D816V inhibitor would be the first targeted therapy for this population if approved, distinct from avapritinib, which covers advanced systemic mastocytosis only.
The phase 2 SUMMIT trial met its 24-week primary endpoint (MS2D2 total symptom score) and all key secondary endpoints, including significant reductions in tryptase, KIT D816V variant allele frequency, and marrow mast cell burden. Benefits deepened through 48 weeks, with a safety profile consistent with KIT inhibitor class effects.
The FDA granted Fast Track designation to BW-20805, an investigational siRNA therapy targeting hepatic prekallikrein, for HAE. Argo Biopharma announced the designation on March 16, 2026, as the therapy continues evaluation in an ongoing phase 2 trial across 3 dosing regimens in adults with HAE type 1 or 2.
As of February 2026, 80% of participants remained attack-free, with time-normalized HAE attack rate reductions ranging from 89% to 100% depending on dosing regimen. Prekallikrein levels declined 90% to 97% within the first month. A phase 3 trial is planned following primary completion later in 2026.
Updated Guidelines in HAE & Epinephrine Use
New international pediatric HAE guidance recommends oral sebetralstat (Ekterly) as first-line on-demand therapy for acute attacks in adolescents aged ≥ 12 years. The recommendation is supported by phase 3 KONFIDENT trial data showing a mean time to symptom relief of 1.79 hours.
The guideline emphasizes early treatment at symptom onset, universal on-demand therapy access regardless of attack severity or location, and maintaining supply for ≥ 2 attacks even during prophylaxis. Sebetralstat remains unapproved for children under 12 years; the ongoing KONFIDENT-KID trial is evaluating its use in ages 2 to 11.
Related: Updated Anaphylaxis Guidelines, Early Management Priorities
A 34-member international panel developed Delphi-based consensus recommendations addressing when patients should administer epinephrine for acute allergic reactions, aiming to reduce variation across existing anaphylaxis action plans. Of 24 clinical scenarios spanning cutaneous, respiratory, cardiovascular, and gastrointestinal involvement, 21 reached consensus favoring epinephrine administration.
Agreement was strongest for reactions involving multiple organ systems or isolated severe respiratory or cardiovascular symptoms. Isolated mild cutaneous or gastrointestinal symptoms did not reach consensus for epinephrine use. Real-world data cited show only 21% of children and 7% of adults receive epinephrine before emergency department arrival, underscoring persistent underuse.
