New Data Demonstrate the Benefits of Early Use of UPTRAVI® (selexipag) in Delaying Disease Progression in a Broad Population of Patients with Pulmonary Arterial Hypertension (PAH)

New Data Demonstrate the Benefits of Early Use of UPTRAVI^® (selexipag) in Delaying Disease Progression in a Broad Population of Patients with Pulmonary Arterial Hypertension (PAH)

Post-hoc pooled data analysis of PAH patients suggests that targeting the prostacyclin pathway with selexipag within a short timeframe after diagnosis may reduce the risk of disease progression[1]^,[2]

PAH is a rare, progressive, and life-threatening condition with no cure; preventing disease progression is a key treatment goal[3]^,[4],[5]

ALLSCHWIL, Switzerland, 30 August 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from a post-hoc pooled analysis of the Phase 3 GRIPHON and Phase 3b TRITON clinical trials evaluating the impact of early initiation of UPTRAVI^® (selexipag) on disease progression, in a large population of PAH patients.

Featured as an oral presentation at ESC Congress 2021 (organized by the European Society of Cardiology), results from a post-hoc pooled data analysis of PAH patients treated with selexipag within 6 months of diagnosis in the Phase 3 GRIPHON and Phase 3b TRITON clinical trials showed that early initiation of selexipag reduced the risk of disease progression (first event) by 52 percent compared with the control group (hazard ratio [HR] 0.48; 95 percent confidence interval [CI] 0.35, 0.66; n = 649).^1,2

“PAH is a rare, progressive and life-threatening condition for which there is no cure. Preventing disease progression and maintaining low-risk status for PAH patients is therefore vitally important, and proactive treatment planning is essential to effectively utilize available therapies,” said Dr. Gerry Coghlan, Consultant Cardiologist at The Royal Free Hospital, London, UK.^* “The GRIPHON and TRITON pooled analysis results support the principle of earlier treatment escalation with therapies targeting the prostacyclin pathway, such as selexipag, if we are to prevent disease progression events and improve long-term patient outcomes.”

Due to the rare nature of the condition, people living with PAH are typically diagnosed in an advanced stage with severe symptoms and a poor prognosis.³ The overall treatment goal for people living with PAH is achieving or maintaining a low-risk status.⁴ Combination therapy (using two or more classes of drugs simultaneously) is recommended in clinical guidelines, based on a strong body of evidence, to help improve symptoms and function early, and prevent disease progression events.^4,[6]

The GRIPHON and TRITON pooled analysis involved patients who had been diagnosed with PAH within six months of randomization (n = 649; 404 from GRIPHON and 245 from TRITON). A comparison was made between those on active therapy with selexipag (n = 329) and those on control therapy with placebo (n = 320).^1,2 Disease progression endpoints were as defined in the GRIPHON and TRITON studies:² time from randomization to the first morbidity event or death (all causes) up to seven days after the last study drug intake.[7]^,[8]^,[9] Selexipag or placebo (control) were given as part of triple therapy (with an endothelin receptor antagonist [ERA] and phosphodiesterase 5 inhibitor [PDE5i]) in 44 percent, double therapy (with an ERA or PDE5i) in 32 percent and as monotherapy in 24 percent of patients.^†1,2

Selexipag reduced the risk of disease progression (first event) by 52 percent compared with the control group (HR 0.48 [95 percent CI 0.35, 0.66]; n = 649). There were 67 patients (20 percent) in the selexipag group and 116 patients (36 percent) in the control group who experienced a disease progression event.^1,2

Among patients who received selexipag on top of double therapy (triple therapy group), risk of disease progression was reduced by 48 percent compared with the double therapy control group (n = 285; 145 in the selexipag group and 140 in the placebo control group; HR: 0.52 [95 percent CI 0.30, 0.92]).²

“At Janssen, we are committed to advancing scientific and clinical knowledge to enhance approaches to PAH treatment and care. This analysis reinforces the role of selexipag in early treatment escalation to help reduce the risk of disease progression and improve long-term outcomes for people living with PAH,” said Alessandro Maresta, M.D., Vice President and Head of Medical Affairs, Pulmonary Hypertension Therapeutic Area, Janssen.^‡ “We will continue to invest in science, research and collaboration with the medical community, as we work towards our ambition of transforming PAH into a long-term, manageable condition.”

Adverse events (AEs) reported in the GRIPHON and TRITON clinical trials were consistent with the known safety profiles of the studies’ medications.^7,8

^*Dr Coghlan has provided paid consultancy services for Janssen in relation to research and advisory boards. He has not been compensated for any media work.

^†HRs and 95 percent CI for time to first disease progression event up to end of double-blind treatment (selexipag/placebo) plus seven days were estimated using a Cox regression model which included treatment as a factor, and baseline prognostic factors and study as covariates.²

^‡Alessandro Maresta is an employee of Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson.

[1] Coghlan GJ, Gaine S, Channick RN, et al. Treatment effect of selexipag on time to disease progression when initiated early in pulmonary arterial hypertension (PAH) patients: GRIPHON and TRITON pooled analysis. Abstract of presentation at European Society of Cardiology (ESC) Congress, 27-30 August 2021.

[2] Coghlan GJ, Gaine S, Channick RN, et al. Treatment effect of selexipag on time to disease progression when initiated early in pulmonary arterial hypertension (PAH) patients: GRIPHON and TRITON pooled analysis. Oral presentation at European Society of Cardiology (ESC) Congress, 27-30 August 2021.

[3] Vachiery JL, Gaine S. Challenges in the diagnosis and treatment of pulmonary arterial hypertension. Eur Respir Rev. 2012;21:313-320.

[4] Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2016;37:67-119.

[5] Hoeper MM, Gibbs JS. The changing landscape of pulmonary arterial hypertension and implications for patient care. Eur Respir Rev. 2014;23:450-457.

[6] Klinger JR, Elliott CG, Levine DJ, et al. Therapy for pulmonary arterial hypertension in adults: update of the CHEST Guideline and Expert Panel Report. Chest. 2019;155:565-586.

[7] Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension N Engl J Med. 2015;373:2522–2533.

[8] Chin KM, Sitbon O, Doelberg M, et al. Efficacy and safety of initial triple oral versus initial double oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension (PAH): results of the randomized controlled TRITON study. Am J Respir Crit Care Med. 2020;201:A2928.

[9] ClinicalTrials.gov. The efficacy and safety of initial triple versus initial dual oral combination therapy in patients with newly diagnosed pulmonary arterial hypertension (TRITON). NCT02558231. Available at: https://clinicaltrials.gov/ct2/show/NCT02558231 Last accessed August 2021.