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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

OPSYNVI® (macitentan and tadalafil)

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OPSYNVI - Background Therapy

Last Updated: 11/15/2024

SUMMARY

Patients were included in the A DUE study if they were either pulmonary arterial hypertension (PAH)-specific treatment-naïve or on a stable dose (≥3 months) of prior endothelin receptor antagonist (ERA; bosentan, macitentan, or ambrisentan) or phosphodiesterase-5 inhibitor (PDE-5i; sildenafil, tadalafil, or vardenafil) monotherapy before baseline right heart catheterization (RHC).¹^,²
- Of the 70 patients randomized to OPSYNVI _M (OPSYNVI group used for comparison versus macitentan 10 mg), 21 were on prior ERA therapy at baseline. Of the 86 patients randomized to OPSYNVI _T (OPSYNVI group used for comparison versus tadalafil 40 mg), 37 were on prior PDE-5i therapy at baseline.¹

CLINICAL DATA

The A DUE Study

A DUE was a prospective, multicenter, double-blind, randomized, active-controlled, triple-dummy, parallel group, group-sequential, adaptive phase 3 study (NCT03904693) that evaluated the efficacy and safety of OPSYNVI as a single-tablet combination therapy (STCT) vs macitentan 10 mg and tadalafil 40 mg monotherapies in patients with PAH, including treatment-naïve patients and patients on prior ERA or PDE-5i monotherapy at baseline (see Figure: Study Design).¹

Study Design²

A diagram of a medical procedure

Description automatically generated with medium confidence

Abbreviations: ERA, endothelin receptor antagonist; FDC, fixed-dose combination; PDE-5i, phosphodiesterase-5 inhibitor.

^aTitration period: Individual tablets of macitentan 10 mg and tadalafil 20 mg were given during week 1 and macitentan 10 mg and tadalafil 40 mg during week 2; from day 15, OPSYNVI was given as a single-tablet; tadalafil uptitration was not performed in patients receiving prior PDE-5i monotherapy.
^bOpen-label titration period: Patients who received macitentan 10 mg monotherapy in the double-blind treatment will receive individual tablets of macitentan 10 mg and tadalafil 20 mg in week 1 of the open-label period, and tadalafil will be uptitrated to 40 mg in week 2. Patients who received tadalafil 40 mg monotherapy during the double-blind treatment will receive individual tablets of macitentan 10 mg and tadalafil 40 mg in weeks 1 and 2 of the open-label period.
^cPatients who prematurely discontinued the double-blind study treatment will continue until the end of safety follow-up but will not receive the open-label treatment.

Adult patients (aged ≥18 years) were included in the study if they were either PAH-specific treatment-naïve (PAH-specific treatment defined as prescribing prostanoids, prostacyclin receptor agonists, guanylate cyclase stimulators, ERAs, or PDE-5is to treat PAH³) or on a stable dose (≥3 months) of prior ERA (bosentan 250 mg total daily dose, macitentan 10 mg total daily dose, and ambrisentan 10 mg total daily dose) or PDE-5i (sildenafil 60-120 mg total daily dose, tadalafil 40 mg total daily dose, and vardenafil 10 mg total daily dose) monotherapy before baseline RHC.²

Patients were excluded if they were treated with the following: a soluble guanylate cyclase stimulator, L-arginine, any form of prostanoids or prostacyclin-receptor agonists (including oral, inhaled, or infused routes) in the 3-month period before starting treatment; combination therapy of ERA and PDE-5i in the 3-month period before starting treatment; other therapies such as initiation of calcium channel blocker or change of dose within 3 months prior to RHC at screening.³

Of the 294 patients screened between October 15, 2019, and August 23, 2022, 187 were randomized. Overall, 108 patients were assigned to receive OPSYNVI, of whom 70 were randomized to OPSYNVI _M that was compared with the 10 mg macitentan monotherapy group (n=35) and 86 patients were randomized to OPSYNVI _T that was compared with the 40 mg tadalafil monotherapy group (n=44).¹ Information regarding patients on background therapy at baseline is summarized in Table: Background PAH Therapy at Baseline.

Background PAH Therapy at Baseline¹

Characteristic	OPSYNVI_M (n=70)	Macitentan (n=35)	OPSYNVI_T (n=86)	Tadalafil (n=44)
PAH therapy at baseline, n (%)
Treatment-naïve	49 (70)	24 (69)	49 (57)	25 (57)
Prior ERA^a	21 (30)	11 (31)	-	-
Macitentan	10 (14)	5 (14)	-	-
Ambrisentan	7 (10)	3 (9)	-	-
Bosentan	4 (6)	3 (9)	-	-
Prior PDE-5i^a	-	-	37 (43)	19 (43)^b
Sildenafil	-	-	28 (33)	11 (25)
Tadalafil	-	-	5 (6)^c	4 (9)
Sildenafil citrate	-	-	5 (6)	3 (7)
Note: Data presented for the full analysis set. Abbreviations: ERA, endothelin receptor antagonist; OPSYNVI_M, OPSYNVI group used for comparison versus macitentan; OPSYNVI_T, OPSYNVI group used for comparison versus tadalafil; PAH, pulmonary arterial hypertension; PDE-5i, phosphodiesterase type-5 inhibitor. ^aPrior medication is defined as any treatment for which the end date is prior to the first dose of study treatment. Additional prior medications received were the following: OPSYNVI_M group: n=1 iloprost, n=1 riociguat, n=1 sildenafil, n=1 tadalafil; OPSYNVI_T group: n=1 riociguat. Some PAH-specific medications were received on the first day of study treatment: OPSYNVI_M group: n=1 macitentan; Macitentan group: n=1 macitentan, n=1 bosentan; OPSYNVI_T group: n=1 sildenafil, n=1 sildenafil citrate; Tadalafil group: n=1 sildenafil citrate. ^bOne prior PDE-5i patient had missing therapy start date and was not included. ^cOne patient who was stratified incorrectly as treatment-naïve received tadalafil until 2 days prior to randomization.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 25 March 2024.

References

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1	Grünig E, Jansa P, Fan F, et al. Randomized trial of macitentan/tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83(4):473-484.
2	Grünig E, Jansa P, Fan F, et al. Supplement to: Randomized trial of macitentan/tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83(4):473-484.
3	Actelion Pharmaceuticals Ltd. Macitentan/tadalafil, pulmonary arterial hypertension, Protocol AC-077A301. Actelion Pharmaceuticals Ltd. EDMS-RIM-263896, 5.0. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2022 November 24]. Available from: https://cdn.clinicaltrials.gov/large-docs/93/NCT03904693/Prot_000.pdf NLM Identifier: NCT03904693.