Pulmonology Month in Review | January 2025

In the field of pulmonology, there have been several important developments that have been covered by the HCPLive editorial team during the month of January 2025. This month in review highlights certain research, including new advances in working to better diagnose asthma, and pivotal trial data for pulmonary arterial hypertension (PAH) and chronic obstructive pulmonary disease (COPD).

Improving Asthma Diagnoses

Elevated Serum cAMP Findings May Allow Asthma Diagnosis by Blood Test
New research has found that cyclic adenosine monophosphate (cAMP) is highly elevated in the blood of people with asthma, enabling diagnosis and possibly severity determination with a simple blood test.

Looking at serum cAMP levels between severity groups, the investigators found no significant difference between severe asthma and nonsevere asthma serum cAMP levels but each asthma group showed significantly higher cAMP levels (adjusted P < .00001) than the non-asthma group. They did not find any significant associations between serum cAMP levels and clinical traits of asthma, however, serum cAMP levels did arithmetically increase with the number of inhaled corticosteroids puffs and controllers used and, in the nonsevere asthma group, with the increases of post-bronchodilator lung function.

Nasal Epithelial Gene Expression May Allow Nasal Swab Diagnosis of Asthma Subtypes
New research has demonstrated proof of concept of using nasal epithelial gene expression to identify asthma endotypes in young people and revealed a predominant T2-low asthma endotype in ethnic minorities.

Celedón and colleagues identified 3 transcriptomic profiles: high T2 expression (T2HIGH), high T17 expression (T17HIGH), and low expression of both pathways (T2LOW/T17LOW). They found that across studies, T2HIGH was present in 23% to 29% of participants, T17HIGH in 35% to 47%, and T2LOW/T17LOW in 30% to 38%. Participants with the T2HIGH profile in each study had higher median total IgE and blood eosinophils than those with the T2LOW profiles (IgE, 584-869 vs 105-382 IU/mL; eosinophils, 343-560 vs 164-413 cells/mL).

Highs and Lows in Pivotal Trial Data for PAH, COPD

Merck Halts Phase 3 HYPERION Trial of Sotatercept for Final Analysis

Merck has halted the Phase 3 HYPERION trial evaluating sotatercept-csrk (WINREVAIR) versus placebo in adults with recently diagnosed PAH and plans to proceed with the final analysis.

Merck indicated the decision to stop HYPERION before its scheduled end date was based on positive data from the interim analysis of ZENITH and an overall review of data from the sotatercept clinical trial program. ZENITH was a global, double-blind, placebo-controlled ZENITH trial evaluated sotatercept added to maximally tolerated background PAH therapy on time to the first event of all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥24 hours, in participants with WHO FC III or IV PAH at high risk of mortality.

Tezepelumab Fails Study Endpoint of Reducing Moderate-to-Severe COPD Exacerbations

Tezepelumab was not seen to reduce the annualized rate of moderate or severe COPD exacerbations, thus failing the primary endpoint of COURSE, a phase 2a trial (NCT04039113).

Singh and colleagues found that the annualized rate of moderate or severe COPD exacerbations over 52 weeks was 1.75 in the tezepelumab group compared with 2.11 in the placebo group (rate ratio, 0.83 [90% CI, 0.64–1.06]; one-sided P = .10), which represented a nonsignificant change and thus did not meet the trial’s primary endpoint.

New Asthma Drug Under Investigation

The FDA has cleared Kinaset Therapeutics’ investigational new drug (IND) clearance for frevecitinib (KN-002), a novel inhaled dry powder therapeutic in development for patients with asthma that remains inadequately controlled by standard of care inhaled maintenance therapies.

Frevecitinib previously demonstrated clinically relevant reductions in fractional exhaled nitric oxide (FeNO) in phase 1b studies including in participants with blood eosinophil counts below 300 cells/ mm³, as well as patients below 150 cells/mm³. The studies also demonstrated dose-proportional pharmacokinetics with plasma levels below pharmacologically active concentrations, aligning with the absence of systemic or local safety concerns. Kinaset plans to begin a Phase 2b dose ranging trial evaluating frevecitinib in mid-2025.

Medicare Access Expanded for COPD, Asthma

HHS Targets 15 Drugs for Medicare Part D Negotiations, Including Semaglutide
The US Department of Health and Human Services (HHS), through the Centers for Medicare and Medicaid Services (CMS), announced an additional 15 drugs covered under Medicare Part D for price negotiations in 2025, targeted for chronic conditions including type 2 diabetes, COPD, and schizophrenia.

As circulated by the HHS on January 17, 2025, negotiations with participating drug companies will transpire in 2025, with any negotiated prices becoming effective in 2027, in line with the Inflation Reduction Act (IRA) passed in August 2022.

Drugs to be negotiated include fluticasone furoate, umeclidinium, and vilanterol inhalation powder (Trelegy Ellipta) for COPD and fluticasone furoate / Vilanterol (Breo Ellipta) for COPD and Asthma.