Mixed Asthma Switching Data, Strong IPF Results Presented at ATS 2026

Newly published research in asthma and idiopathic pulmonary fibrosis highlighted a midday panel held on the second day of the American Thoracic Society 2026 International Conference. Researchers presented the findings of their study to a rapt audience as positive results were shown across treatment plans for these prevalent chronic lung conditions.

NIMBLE Trial Finds Depemokimab Switch Outcomes Depend on Prior Biologic

Geoffrey Chupp, MD, a pulmonologist at Yale School of Medicine, began the session with newly released results from the phase 3A NIMBLE trial,¹ which assessed the efficacy of switching patients with severe asthma on mepolizumab or benralizumab to the twice-yearly treatment of depemokimab. This trial aimed to compare an ultra-long-acting biologic against IL-5 treatment

“Asthma biologic studies typically have focused on biologic-naive patients…but in fact, what we are doing in the clinic now a lot is we’re switching patients because we have multiple agents. When we don’t get an optimal response, we switch them from one biologic to another,” said Chupp. “But there really haven’t been any randomized controlled trials that have been properly placebo-controlled to look at this.”

The twice-yearly dosing may also increase adherence, which makes depemokimab an intriguing alternative to current biologics. The NIMBLE trial aimed to determine whether depemokimab was noninferior to being treated with mepolizumab or benralizumab.

Patients were eligible for the NIMBLE trial if they had a diagnosis of asthma for at least 2 years, had previously been treated with mepolizumab or benralizumab for 12 months or more with a reduction in exacerbations or a reduction in maintenance oral corticosteroids, and had a medium- to high-dose inhaled corticosteroid. There were 1717 patients who were randomized 1:1 to receive either depemokimab 100 mg subcutaneously every 6 months with a placebo matching their previous treatment or their current treatment plus a subcutaneous placebo every 6 months.

The primary end point was the annualized rate of clinically significant exacerbations over the course of a year. The researchers were also looking for noninferiority. “This essentially is a statistical approach where you set the upper bounds of the confidence interval, you predict what that’s going to be, and if your study stays within that upper bounds, then you’ve achieved noninferiority,” explained Chupp.

After a year, the upper bound of the CI was exceeded, and the primary end point was not met. There was a treatment difference of 0.08 exacerbations per year (RR, 1.16; 95% CI, 0.98-1.38), which amounted to 1 additional exacerbation every 12.5 years in those who used depemokimab. Patients using depemokimab had a slightly higher probability of an exacerbation through 52 weeks when compared with mepolizumab or benralizumab (36% vs 32%). Secondary end points in quality of life, asthma control, and lung function remained stable through 52 weeks in both treatment arms.

Chupp noted that patients who switched from mepolizumab to depemokimab had identical exacerbations to those who continued on mepolizumab. However, patients who switched from benralizumab to depemokimab had higher rates of exacerbations compared with those who continued on benralizumab, indicating the area where noninferiority was not reached. Those who switched from benralizumab would have a treatment difference of 0.19 exacerbations per year, which equates to an additional exacerbation every 5.3 years. The safety profile of depemokimab was in line with benralizumab and mepolizumab.

“Because we have this data, I think it gives us an opportunity and information that we can use with a patient to properly educate them in a shared decision-making fashion about the risk of switching depending on what the patient is switching from and our decision to support that switch or not,” Chupp concluded.

Inhaled Treprostinil Slows Lung Function Decline in IPF

Steven Nathan, MD, FCCP, medical director of the Advanced Lung Disease Program and Lung Transplant Program at Inova, also discussed the results of the TETON-2 study, which aimed to assess if inhaled treprostinil could improve the forced vital capacity (FVC) of patients living with IPF after treprostinil had previously been shown to work with ILD.²

The TETON program included 2 replicate phase 3 trials that occurred over 52 weeks and enrolled a total of 1195 participants. Eligibility for the study included an FVC that was greater than or equal to 45% predicted and a diagnosis of IPF. Stable background antifibrotics were allowed for all patients. Participants were given either treprostinil or placebo 4 times per day with a 3-breath dosage. The primary end point was the change in absolute FVC from baseline to week 52.

There were 239 participants on placebo and 224 on treprostinil who completed the study, with both groups having similar demographic makeups, with men being the primary participants in both the placebo and treprostinil groups (80.3% and 79.9%, respectively). The study met its primary end point through 52 weeks, showing a difference in FVC of 95.6 mL (95% CI, 52.2-139.0) through 52 weeks. When Nathan showed the combined results of TETON-1 and TETON-2 for the first time, the difference between placebo and treprostinil expanded to 111.8 mL (95% CI, 79.7-144.0).

“The curves separate pretty early,” he said. “Remember, the patients who are doing up titration in the first 4 weeks, and we start to see a bit of a difference as early as 8 weeks into the study.”

The combined data for the primary end point found a change in FVC of –45.4 in the treprostinil group compared with –161.7 in the placebo group. Background therapy also played a part in differences in FVC, as the median change from baseline was smaller in those taking treprostinil regardless of background therapy. In the combined data from TETON-1 and TETON-2, patients taking Treprostinil had a median change of FVC from baseline of –52.6 when not on background therapy, –37.9 when using background nintedanib, and –46.7 when using background pirfenidone. Those using placebo had changes of –141.1, –130.4, and –217.4 in those respective groups.

There were many adverse events in patients taking the treatment, with 91.6% of those using treprostinil experiencing an adverse event compared with 89.5% in the placebo group. The number of participants that had adverse events that led to death was 3.4% in the treatment group and 7.5% in the placebo group.

“In conclusion, inhaled treprostinil demonstrated a statistically significant 95.6 mL placebo-corrected difference in FVC at 52 weeks,” said Nathan. “There was a statistically significant difference at 52 weeks for a number of the secondary endpoints, including clinical worsening, percent predicted FVC, the [King’s Brief Interstitial Lung Disease questionnaire], and the [lung diffusion test].”

Overall, these results provide alternatives for patients with severe asthma and IPF to take treatments that may work better for them. With more options to choose from, patients can have a hand in choosing the medication that works best for them.

References

1. Chupp G, Nagase H, Skowasch D, et al; NIMBLE Study Investigators. Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: a multicenter, randomized, double-blind, phase 3A clinical trial (NIMBLE). Am J Respir Crit Care Med. 2026;212(5):921-935. doi:1093/ajrccm/aamag031
2. Nathan SD, Smith P, Deng C, et al; TETON-2 Trial Investigators. Inhaled Treprostinil for idiopathic pulmonary fibrosis. N Engl J Med. Published online March 11, 2026. doi:10.1056/NEJMoa2512911