Contact your
Local MSL
Request A Medical Science
Liaison (MSL)
Contact your
Local MSL
Request A Medical Science
Liaison (MSL)

SERAPHIN: Primary endpoint in overall study population*

OPSUMIT® (macitentan) significantly reduced the risk of disease progression by 45% vs placebo1

The primary endpoint in the SERAPHIN trial was time to the first occurrence of death, a significant morbidity event, defined as atrial septostomy, lung transplantation, initiation of IV or SC prostanoids, or clinical worsening of PAH (defined as all of the following: a sustained ≥15% decrease from baseline in 6MWD, worsening of PAH symptoms, and need for additional PAH treatment) during double-blind treatment plus 7 days.1,2

Kaplan-Meier estimates of risk of first primary endpoint event in SERAPHIN1,2

Primary SERAPHIN endpoint: Kaplan-Meier estimates of risk of disease progression

Summary of primary endpoint events1

  OPSUMIT® 10 mg
(n=242), n (%)
Placebo
(n=250), n (%)
Patients with a primary endpoint event§ 76 (31.4) 116 (46.4)
Component as first event
Worsening PAH 59 (24.4) 93 (37.2)
Death 16 (6.6) 17 (6.8)
Initiation of IV/SC prostanoids 1 (0.4) 6 (2.4)

The beneficial effect of OPSUMIT® was primarily attributable to a reduction in clinical worsening events (defined as all of the following: a sustained ≥15% decrease from baseline in 6MWD,† worsening of PAH symptoms [a decline in WHO FC], and need for additional PAH treatment).


§No patients experienced an event of lung transplantation or atrial septostomy in the placebo or OPSUMIT® 10 mg treatment groups.

OPSUMIT® can be started as monotherapy or in combination with PDE-5is or inhaled prostanoids.

ǁOPSUMIT® is approved in combination with PDE-5is or inhaled prostanoids, but not oral prostanoids.1

Combination therapy exploratory subgroup analysis in SERAPHIN trial

The combination therapy data below represent an exploratory analysis. Results should be interpreted with caution.

Kaplan-Meier estimates of risk of primary endpoint event when OPSUMIT® was added to stable PAH-specific background therapy1,3

At baseline, 64% of enrolled patients were treated with a stable dose of PAH-specific background therapy (61% PDE-5is; 6% inhaled or oral prostanoids).

ǁOPSUMIT® is approved in combination with PDE-5is or inhaled prostanoids, but not oral prostanoids.1

Kaplan-Meier estimates of risk of first primary endpoint event1,3,4

Combination therapy exploratory analysis: estimates of risk of first primary endpoint event graph

Not adjusted for multiplicity.

Summary of primary endpoint events in patients treated with PAH-specific background therapy4

  OPSUMIT® 10 mg
(n=154), n (%)
Placebo
(n=154), n (%)
Patients with a primary endpoint event§ 50 (32.5) 68 (44.2)
Component as first event
Worsening PAH 39 (25.3) 58 (37.7)
Death 10 (6.5) 6 (3.9)
Initiation of IV/SC prostanoids 1 (0.6) 4 (2.6)

§No patients experienced an event of lung transplantation or atrial septostomy in the placebo or OPSUMIT® 10 mg treatment groups.

Common adverse reactions in the combination therapy exploratory subgroup5#

  OPSUMIT® 10 mg
n=154
Placebo
n=153
Anemia 16.2% 4.6%
Nasopharyngitis 11.0% 10.5%
Bronchitis 11.0% 5.9%
Headache 13.6% 10.5%
Diarrhea 13.0% 9.8%

#More frequent than placebo by ≥3%.

Combination therapy exploratory subgroup safety2,5

  • The safety profile of OPSUMIT® as part of a combination therapy regimen was consistent with that of OPSUMIT® in the overall SERAPHIN population
  • The incidence of peripheral edema, a known ERA-related adverse event, was similar in patients receiving background therapy who were treated with OPSUMIT® and placebo (19.5% and 23.5%, respectively)
  • Treatment discontinuations due to adverse events in patients receiving background therapy were similar in those receiving OPSUMIT® and those receiving placebo (9.1% and 11.8%, respectively)

Looking for patient enrollment resources?

Enroll Patients

SERAPHIN PAH-related hospitalization results

View the Data

View SERAPHIN PAH-CTD subgroup data

See the Data

Review the
REPAIR study

DISCOVER THE DATA

BACK TO TOP

*All randomized patients.

Confirmed by a 6-minute walk test performed on a different day within 2 weeks.

Worsening of PAH included at least one of the following: Advancing to a higher FC from baseline (or no change in WHO FC IV) and signs of right heart failure that does not respond to oral diuretic treatment.

6MWD=6-minute walk distance; CI=confidence interval; ERA=endothelin receptor antagonist; FC=Functional Class; HR=hazard ratio; IV=intravenous; PAH=pulmonary arterial hypertension; PDE-5i=phosphodiesterase type 5 inhibitor; SC=subcutaneous; SERAPHIN=Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve CliNical Outcome; WHO=World Health Organization.
References: 1. OPSUMIT® [prescribing information]. Actelion Pharmaceuticals US, Inc. 2. Pulido T, Adzerikho I, Channick RN, et al; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809-818 and suppl 1-21. doi:10.1056/NEJMoa1213917 3. US Dept of Health and Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research. Opsumit® (macitentan) NDA 204410. Accessed October 14, 2022. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204410Orig1s000MedR.pdf 4. Data on file. Actelion Pharmaceuticals US, Inc. 5. Jansa P, Pulido T. Macitentan in pulmonary arterial hypertension: a focus on combination therapy in the SERAPHIN trial. Am J Cardiovasc Drugs. 2018;18:1-11.

EXPAND +

+ +