Dupilumab, Depemokimab, and COPD: What APPs See in Practice

Biologic therapy has fundamentally transformed the management of severe asthma, with 7 approved agents now spanning 4 mechanistic targets — anti-IgE (omalizumab), anti-IL-4/IL-13 (dupilumab), anti-IL-5 and anti-IL-5 receptor (mepolizumab, benralizumab, reslizumab, and depemokimab), and anti-TSLP (tezepelumab) — and long-term extension studies demonstrating durable exacerbation reductions of 45% to 70% over 3 to 4 years.¹

The December 2025 FDA approval of depemokimab (Exdensur; GSK), the first biologic in any class dosed every 6 months, introduced a novel adherence and access paradigm built on SWIFT-1 and SWIFT-2 data showing 58% and 48% annualized exacerbation reductions, respectively.² The chronic obstructive pulmonary disease (COPD) biologic landscape has expanded similarly: dupilumab was formally incorporated into GOLD 2025 at a blood eosinophil threshold of 300 cells/µL or greater in patients with chronic bronchitis on maximal triple inhaled therapy, supported by BOREAS and NOTUS demonstrating 30% to 34% exacerbation reductions and a distinctive FEV1 improvement of 62 to 83 mL — a signal not replicated with IL-5 antagonism.³,⁴

Mepolizumab subsequently received COPD approval and was incorporated into GOLD 2026, with the MATINEE trial providing the pivotal data establishing its 18% to 21% exacerbation reduction benefit and broadening the eosinophil threshold to 150 cells/µL.⁵ Despite this expanding evidence base, real-world biologic prescribing in asthma and COPD remains heavily constrained by insurance formulary decisions, documentation burden, and access gaps — challenges that fall disproportionately on advanced practice providers who in many settings are the sole or primary pulmonary clinicians managing these patients.

Against this backdrop, HCPLive convened a panel of advanced practice providers from across the United States for a virtual roundtable on biologic therapy in asthma and COPD. The forum was moderated by Melissa Dolbec, NP, a nurse practitioner at the Oregon Clinic in Portland with a focus on pulmonary hypertension and a background in general pulmonology, and included peers representing academic medical centers, multi-specialty community groups, rural solo practices, and hospital medicine across Oregon, Iowa, Tennessee, Idaho, Minnesota, California, Louisiana, and Ohio, providing a granular view of how biologic therapy is accessed, administered, and navigated across heterogeneous payer environments. The discussion was structured around four interactive polling questions and open exchange, spanning OCS burden thresholds for biologic escalation, agent selection rationale, mucus plugging data, and the distinct practical landscape of COPD biologics.

How Are APPs Navigating Formulary Barriers?

The panel's most consistent and candid finding was that insurance formulary, not clinical pharmacology, determines which biologic patients receive in most real-world practice settings. A polling question on biologic selection drivers returned biomarkers as the top-cited factor (53.8%) and clinical phenotype second (46%), but open discussion immediately shifted to the practical reality: as 1 panelist put it, "the person at the insurance company who failed organic chemistry chooses it for me."

Panelists described selecting agents based on what is most likely to be approved, using comorbidities (nasal polyps, atopic dermatitis, eosinophilic esophagitis) to pursue alternative indications when asthma approval fails, and delegating the selection process entirely to embedded pharmacists via medication therapy management (MTM) consults — a workflow Sara Kraus, NP, described as allowing her to simply refer patients for pharmacist review and receive a managed approval outcome without direct involvement in the prior authorization process. A standout operational innovation emerged when Kraus described the Epic-integrated Evidently AI tool, which allows natural-language search of entire patient records for eosinophil counts, prednisone prescriptions, and clinical history — dramatically accelerating the tracking of cumulative OCS exposure from external providers such as urgent care and primary care settings, where most panelists reported receiving no notification when steroids are prescribed.

Dolbec relayed a related insight from an MSL interaction: biologic manufacturers maintain dedicated formulary advocacy teams that will challenge insurance companies on coverage decisions — a resource most panelists were unaware they could activate. The forum reinforced that the biologic escalation conversation should begin with the first OCS burst, well before GINA's step 5 phenotyping recommendation: as Stephanie Arceneaux, NP, noted, "If we're waiting that long to phenotype them and endotype them, and it's almost too late, how many pulse doses of steroids have they received?" — a statement consistent with retrospective data suggesting measurable long-term morbidity with as few as 3 lifetime OCS bursts.

Depemokimab's Q6-month, office-administered dosing was identified as particularly appealing for needle-phobic patients, college students home on academic breaks, and non-adherent patients in whom guaranteed administration eliminates uncertainty about self-injection compliance. Brian Bizik, PA, offered an important mechanistic clarification that had direct clinical implications: adverse reaction duration with biologics is governed by host depletion dynamics — the reservoir of available histamine, leukotrienes, and other mediators — not by the drug's half-life; an adverse event with a 6-month drug does not last 6 months any more than a Q4-week drug's adverse events last 4 weeks.²

How to Manage Patient Expectations With COPD Biologics?

The COPD discussion surfaced a consistent theme: biologic therapy in COPD is clinically meaningful but subjectively difficult for patients to perceive, and expectation management is as important as agent selection. Dupilumab emerged as the near-universal first-choice agent across the panel, driven by faster insurance approval timelines, greater prescriber familiarity, and consistent outcomes data — while mepolizumab was positioned as a practical alternative when insurance approves it preferentially at lower eosinophil thresholds.

The BOREAS and NOTUS FEV1 improvement signal of 62 to 83 mL — absent from mepolizumab's COPD trial program — was identified as a meaningful differentiating feature for panelists who discuss functional outcomes with patients, though several noted that the core clinical argument for COPD biologics is exacerbation prevention, not symptom relief.³ As Bizik framed it: "Exacerbations are not like with asthma — they're life-changing, life-altering, lung volume losing events that they never come back from. So they're one-way streets, nobody comes back from an exacerbation like they were before."

An underappreciated clinical observation raised during the discussion was comorbidity unmasking: as biologic therapy effectively suppresses inflammatory exacerbations in COPD, previously occult conditions — left heart disease, pulmonary hypertension, and severe deconditioning — may emerge as the residual source of dyspnea. Ensifentrine (Ohtuvayre; Verona/Merck) access was described as consistently poor across the panel, with patient assistance programs reportedly exhausted and prior authorization success through the designated specialty pharmacy declining — a practical barrier to a therapeutic option that several panelists saw as valuable for patients not meeting biologic eosinophil thresholds.

The panel identified 4 high-priority unmet needs: validated biologic de-escalation protocols in both asthma and COPD; patient-centered quality of life data capturing personally meaningful functional goals rather than validated questionnaire scores alone; real-world effectiveness evidence for COPD biologics and ensifentrine to support patient motivation and payer conversations; and renewed investment in pulmonary rehabilitation, which multiple panelists characterized as dramatically underutilized relative to its evidence base and for which NP and PA prescribing authority remains legislatively incomplete in some states.

References

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2025. Accessed July 2026. https://ginasthma.org

2. Jackson DJ, Wechsler ME, Menzies-Gow A, et al; SWIFT-1 and SWIFT-2 Investigators. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N Engl J Med. 2024;391(24):2337–2349. doi:10.1056/NEJMoa2406673

3. Bhatt SP, Rabe KF, Hanania NA, et al; BOREAS Investigators. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023;389(3):205–214. doi:10.1056/NEJMoa2303951

4. Bhatt SP, Rabe KF, Hanania NA, et al; NOTUS Study Investigators. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. N Engl J Med. 2024;390(24):2274–2283. doi:10.1056/NEJMoa2401304

5. Sciurba FC, Criner GJ, Christenson SA, et al; MATINEE Investigators. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N Engl J Med. 2025;392(17):1710–1720. doi:10.1056/NEJMoa2413181