Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication UPTRAVI is a prostacyclin receptor agonist indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I): In adults to delay disease progression and reduce the risk of hospitalization for PAH. ( 1.1 ) In pediatric patients aged 2 years and older. UPTRAVI reduces NT-proBNP and is expected to delay disease progression and reduce the risk of hospitalization for PAH. FDA label
Also known as selexipag (Uptravi), Selexipag (adult formulation), oral selexipag (Uptravi), JNJ-67896049, ACT-293987, Uptravi
selexipag · 9 trials · 7 indications
Number of participants with TEAEs were reported. Adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days. Data includes all TEAEs irrespective of whether they were serious or non-serious.
Number of participants with TEAEs leading to premature discontinuation of selexipag were reported. AE was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as AEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days.
Number of participants with TESAEs were reported. AE was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. TESAEs were defined as TSAEs occurring at or after the initial administration of study intervention through the day of last dose plus 3 days.
Number of participants with treatment-emergent deaths during the study were reported.
Number of pregnant females with maternal exposure to selexipag were reported.
Time to disease progression: time from randomization to first Clinical Event Committee (CEC)-confirmed disease progression event occurring between date of randomization until double-blind end date (DBED) + 7 days. Disease progression event as adjudicated by CEC, defined as any of the following: death (all causes); atrial septostomy or Potts' anastomosis, or registration on lung transplant list; hospitalization due to worsening pulmonary arterial hypertension (PAH); clinical worsening of PAH. Clinical worsening of PAH was defined as initiation of new PAH-specific therapy or intravenous diuretics or continuous oxygen use and at least 1 of the following: worsening in World Health Organization (WHO) functional class (FC); new occurrence or worsening: of syncope, of at least 2 PAH symptoms (shortness of breath/dyspnea, chest pain, cyanosis, dizziness/near syncope, or fatigue), of signs of right heart failure not responding to oral diuretics. Kaplan-Meier method was used for estimation.
A sustained treatment transition is considered if the 3 following criteria are met a) being on study treatment (selexipag) at Week 16, and b) not having a study treatment interruption(s) of a total of 8 days or more prior to Week 16, and c) absence of inhaled treprostinil or any prostanoid treatment after Week 8 up to Week 16. The percentage of subjects with a sustained treatment transition is calculated with 95% confidence interval (CI) using the Clopper-Pearson method.
Percentage of subjects with treatment-emergent AEs (serious and non serious), regardless of relationship to selexipag
Number of subjects with adverse events leading to premature discontinuation of selexipag is determined from the first dose of selexipag up to the last dose of selexipag
Both systolic(SBP) and diastolic (DBP) arterial blood pressure were measured in a sitting position after at least 5 minutes of rest at scheduled time points. Median change from baseline to pre-specified post-baseline visits are calculated
Pulse rate is measured after at least 5 minutes of rest in a sitting position. Median change from baseline to pre-specified post-baseline visits are calculated.
This is the individual maximal tolerated dose (MTD) observed at Week 12 in the subjects still on selexipag at Week 16. MTD is defined as the dose of selexipag reached with the last dose change up to Week 12
Median time from baseline (Day1) to the end of down-titration of inhaled treprostinil is calculated
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A TEAE is any AE temporally associated with the use of study drug (from study drug initiation until 3 days after study drug discontinuation), whether or not considered related to the study drug.
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Those SAEs occurring during study drug administration, that is, between study drug initiation and three days after study drug discontinuation, are defined as treatment-emergent SAEs.
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A TEAE is any AE temporally associated with the use of study drug (from study drug initiation until 3 days after study drug discontinuation), whether or not considered related to the study drug.
Time from randomization to the first occurrence of a morbidity event or death (all causes) was analyzed with the Kaplan-Meier method (event-free KM estimates at different time points). Morbidity event was defined as any of the following events confirmed by the Critical Event committee: * Hospitalization for worsening of pulmonary arterial hypertension (PAH), * Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy, * Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH, * Disease progression which was defined by a decrease in 6-minute walk distance from baseline (\>=15%, confirmed by a 2nd test on a different day) combined with worsening of WHO FC for patients belonging to WHO FC II/III at baseline, or combined with the need for additional PAH-specific therapy for patients belonging to WHO FC III/IV at baseline. Note: The number of patients at risk decreased over time but this cannot be captured below
AUCτ, ss, combined was defined as the area under the plasma concentration-time curve over one dosing interval at steady state. AUCτ,ss,combined was calculated as 1/38 AUCτ,ss,selexipag plus 37/38 AUCτ,ss,ACT-333679.
The number of RP attacks is determined from daily entries in electronic Diaries (eDiary).
Electrocardiograms (ECGs) will be extracted in replicate at predefined timepoints from replicated 12-lead Holter ECGs. Cardiodynamic endpoints will be assessed at steady-state for 800 μg selexipag on Day 11 and at steady-state for 1600 μg selexipag on Day 23. Based on prospective criteria, QTcI will be the primary method for heart rate (HR) correction.
| Arm | Type | Description |
|---|---|---|
| Selexipag | EXPERIMENTAL | Participants will receive selexipag tablets twice daily with the dose strength corresponding to their individual maximum tolerated dose (iMTD) from the parent study. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
| Open-Label Extension Period: Selexipag | EXPERIMENTAL | Participants with a positive benefit/risk ratio of selexipag for PAH will be offered selexipag in the open label extension period. Participants on selexipag during the double-blind treatment period will continue treatment at their iMTD during the OLEP, for those previously on placebo, the iMTD will uptitrate selexipag during first 12 weeks until participant reaches iMTD. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
| Selexipag, Open Label | EXPERIMENTAL | Subjects on inhaled treprostinil treatment participate in a 16-week main treatment period including down-titration of treprostinil to end of Week 8 and parallel up-titration of selexipag to the maximum tolerated dose (MTD) up to Week 12, for each individual patient but not above 1600 mcg twice daily. From Week 12 up to Week 16, patients continue selexipag at their individual MTD. Patients could continue the study drug selexipag during the extended treatment period from Week 16 until commercial availability of selexipag. |
| 1 | EXPERIMENTAL | ACT-293987, twice daily |
| 2 | PLACEBO_COMPARATOR | Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed |
| open label selexipag | EXPERIMENTAL | The first dose of selexipag (Uptravi) will be administered in the evening of Day 1 and will be based on the body weight. Thereafter selexipag will be administered twice daily (morning and evening). Selexipag will be up-titrated during the first 12 weeks, with weekly increments equal to the starting dose until the participants reach their individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline weight category is achieved (which will be 8-fold of the corresponding starting dose). Up-titration is followed by a stable maintenance treatment period from Week 12 to Week 16, at the maximum tolerated dose. Thereafter, participants will be treated with selexipag as long as the treatment is beneficial to the participants, as per investigator's decision. |
| ACT-293987 (NS-304) and matching placebo | EXPERIMENTAL | Subjects will be randomized to the study following screening. Each subject will then undergo an acute hemodynamic study with right heart catheterization after a single oral administration of ACT-293987 (NS-304)on Day 0. The objectives are to collect data about the drug effect on the right heart hemodynamic parameters (PVR, calculated SVR and PVR/SVR) measured by right heart catheterization after single oral dose administration of NS-304 and to assess the safety and tolerability of a single oral dose of NS-304. |
| Group A | EXPERIMENTAL | Subjects in Group A receive selexipag on Days 3 to 23 and moxifloxacin-matching placebo on Days 2 and 24. Selexipag administered orally, twice a day, for 21 days according to the following multiple dose up-titration regimen: 400 μg on Days 3-5, 600 μg on Days 6-8, 800 μg on Days 9-11, 1000 μg on Days 12-14, 1200 μg on Days 15-17, 1400 μg on Days 18-20, and 1600 μg on Days 21-23 (only morning dose on Day 23). |
| Group B1 | EXPERIMENTAL | Subjects in Group B1 receive 400 mg moxifloxacin, orally on Day 2 and moxifloxacin-matching placebo, orally on Day 24. Subjects receive placebo for selexipag, orally on Days 3 to 23. |
| Group B2 | EXPERIMENTAL | Subjects in Group B2 receive moxifloxacin-matching placebo, orally on Day 2 and 400 mg moxifloxacin, orally on Day 24. Subjects receive placebo for selexipag, orally on Days 3 to 23. |
| Name | Type | Description |
|---|---|---|
| Selexipag | DRUG | Selexipag tablets will be administered orally at all dose strengths (200, 400, 600, 800, 1000, 1200, 1400 and 1600 microgram) twice daily. |
| Placebo | DRUG | Matching placebo tablets will be administered orally. |
| Standard of Care (SOC): Endothelin receptor antagonist | DRUG | ERAs will be administered as SOC therapy. |
| SOC: Phosphodiesterase type 5 (PDE-5) inhibitor | DRUG | PDE-5 inhibitor will be administered as SOC therapy. |
| SOC: Soluble guanylate cyclase stimulator | DRUG | Soluble guanylate cyclase stimulator will be administered as SOC therapy. |
| ACT-293987 | DRUG | Tablets, twice daily |
| selexipag (Uptravi) | DRUG | Film-coated tablets for oral administration |
| ACT-293987 (NS-304) | DEVICE | - |
| placebo for selexipag | DRUG | - |
| moxifloxacin | DRUG | - |
| moxifloxacin-matching placebo | DRUG | - |
Inclusion Criteria: * Treated with selexipag at the end of a parent study and: a) the parent study has established efficacy with a favorable benefit/risk profile for the indication under investigation; b) participant may continue to benefit from treatment with selexipag; c) has completed the end of...
Selexipag is used for pulmonary arterial hypertension and is also being studied in pulmonary hypertension, cardiodynamics, and Raynaud's phenomenon secondary to systemic sclerosis. It is a small molecule developed by Johnson & Johnson, which trades under the ticker JNJ. The program spans both adult and pediatric pulmonary arterial hypertension populations.
Selexipag targets PTGIR, the prostacyclin IP receptor, and acts as an agonist at that receptor. PTGIR agonism is the mechanism attributed to selexipag in its development for pulmonary arterial hypertension and related cardiovascular conditions. The drug is a small molecule agonist directed at this receptor.
Selexipag is developed by Johnson & Johnson, which trades under the ticker JNJ. The company is listed as the developer of the selexipag program, which includes trials in pulmonary arterial hypertension and pulmonary hypertension. Selexipag is also known by the name Uptravi.
Selexipag is in Phase 1 development according to its current program listing, and it is investigational rather than approved. Its clinical program includes Phase 2 and Phase 3 trials, with one trial currently active and two completed. The trials together have enrolled 1,253 participants.
Selexipag trials include NCT04565990, a completed Phase 3 study in pulmonary hypertension, and NCT02471183, a completed Phase 3 study of transition from inhaled treprostinil to oral selexipag in pulmonary arterial hypertension. NCT04175600 is an active Phase 3 pediatric add-on study, and NCT03492177 is an active Phase 2 pediatric dose-confirmation study.
Yes, selexipag is also known as Uptravi, and the oral adult formulation is referred to as oral selexipag (Uptravi). Searches for Uptravi, selexipag (Uptravi), or Selexipag (adult formulation) all refer to the same small molecule developed by Johnson & Johnson for pulmonary arterial hypertension.