SAFETY

The INCREASE trial demonstrated that TYVASO® was well tolerated1

Most frequently occurring adverse events (>10% in either group)1

Adverse Event Treatment n (%)
TYVASO n=163 Placebo n=163
Cough 71 (43.6) 54 (33.1)
Headache 45 (27.6) 32 (19.6)
Dyspnea 41 (25.2) 51 (31.3)
Dizziness 30 (18.4) 23 (14.1)
Nausea 25 (15.3) 26 (16.0)
Fatigue 23 (14.1) 23 (14.1)
Diarrhea 22 (13.5) 19 (11.7)
Throat Irritation 20 (12.3) 6 (3.7)
Oropharyngeal Pain 18 (11.0) 4 (2.5)

Discontinuation rates due to an AE were similar for TYVASO and placebo at 9.8% and 8.0%, respectively.2

SAFETY ENDPOINTS

Below is a post hoc analysis of data from a prespecified endpoint. Interpret with appropriate caution. The clinical significance of differences in FVC is unknown.

Impact on lung function in patients taking TYVASO compared with placebo3

  • FVC for patients in overall population3*

  • FVC for patients with an IPF etiology2†

In the overall population, TYVASO resulted in a placebo-corrected difference in FVC of 44.4 mL at week 162

INCREASE trial improved lung function data vs placeboINCREASE trial improved lung function data vs placebo

Based on a concern that treating WHO Group 3 pulmonary hypertension with pulmonary vasodilators could worsen V/Q matching in patients, PFTs (including FVC) and exacerbations were included as safety endpoints due to the potential risk of V/Q mismatch.4

*LS mean (SE) and estimated difference (SE) are from the MMRM with the change from baseline in FVC as the dependent variable; treatment, week, treatment-by-week interaction as the fixed effects; baseline FVC as the covariate; and patient as the random effect. An unstructured variance/covariance structure shared across treatment groups was used to model the within-patient errors.3

During the 16-week study, fewer patients in the TYVASO group had exacerbations of underlying lung disease2‡

Overall, 43 patients (26.4%) in the TYVASO group experienced an exacerbation of underlying lung disease during the study compared with 63 patients (38.7%) in the placebo group2‡

Number of patients who experienced an exacerbation2

Time to exacerbation of underlying lung disease data from INCREASE trialTime to exacerbation of underlying lung disease data from INCREASE trial

There was no evidence that TYVASO, an inhaled vasodilator therapy, worsened oxygenation, suggesting it does not contribute to the undesirable effects of V/Q mismatching.1

Exacerbation was defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality determined by the investigator. Patients who did not experience an exacerbation had their time to exacerbation censored at the study termination date.2

AE=adverse event; FVC=forced vital capacity; IPF=idiopathic pulmonary fibrosis; LS=least squares; MMRM=mixed-effect model repeat measurement; PFT=pulmonary function test; SE=standard error; V/Q=ventilation/perfusion; WHO=World Health Organization.