A combination of Opsumit (macitentan) plus Adcirca (tadalafil) lowered pulmonary vascular resistance — a measure showing how well blood flows through vessels — by 47% in people newly diagnosed with pulmonary arterial hypertension (PAH) and improved their physical capacity, new data show.
Olivier Sitbon, MD, PhD, with Université Paris–Sud presented the results at the CHEST Annual Meeting 2019 on Oct. 22 in New Orleans, in the presentation “Initial Treatment Combination with Macitentan and Tadalafil in Patients with Pulmonary Arterial Hypertension: Results from the OPTIMA Study.”
Opsumit, marketed by Actelion Pharmaceuticals, is an endothelin-receptor antagonist (ERA) that works by reducing the contraction and narrowing of blood vessels, which can help lessen their resistance to blood flow and lower blood pressure in the lungs. Adcirca (marketed by United Therapeutics) is a phosphodiesterase type-5 (PDE-5) inhibitor that works by relaxing the smooth muscle cells of arteries, leading to vasodilation and lower blood pressure.
The Phase 4 open-label OPTIMA trial (NCT02968901) assessed the combination of Adcirca and Opsumit as a first-line — or initial — therapy in newly diagnosed PAH patients.
Participants, a total of 46, had PAH and mild-to-moderate physical impairment due to the disease (WHO functional class II-III). They were given 10 mg of Opsumit and 20 mg of Adcirca, both orally, once daily at the same time. Adcirca dose was increased to 40 mg after eight days.
After 16 weeks, pulmonary vascular resistance was 47% lower than values measured before patients began the treatment. This reduction means that the heart’s right side works less hard to pump blood into the lungs.
“OPSUMIT, in combination with tadalafil, showed a 47% reduction of the primary endpoint of mean pulmonary vascular resistance (PVR) at week 16 compared with baseline in patients with PAH,” Sitbon, the trial’s principal investigator and a professor of respiratory medicine at Université Paris-Sud, said in an Actelion’s press release.
“These data are meaningful because improvement of PVR [pulmonary vascular resistance], an important indicator of right ventricular function, is a key treatment goal,” added Sitbon, who has served as a paid consultant to Actelion.
Moreover, 63% of treated patients showed improved functional ability, walking more meters than before treatment in the six-minute walk distance test, which assesses exercise capacity and endurance.
The number of patients with at least three low-risk criteria also increased, rising from 23.9% (11 out of 46 patients) to 68.2% (30 out of 46 patients).
In general, the combination was well-tolerated. A majority of patients (93.5%) experienced at least one side effect, with the most common being peripheral edema (fluids accumulation; 28.3%), headache (23.9%), diarrhea (19.6%), shortness of breath (15.2%), anemia (13.0%), and lack of energy (13.0%).
Severe adverse reactions were observed in 13 patients; three discontinued treatment due to serious complications and three died during the study, with the causes of death reported as cardiac arrest, heart failure, and multi-organ failure with sepsis.
“Current clinical guidelines for PAH recommend upfront double oral combination therapy, and this study confirms that initial oral dual combination with macitentan and tadalafil is beneficial in those patients,” Sitbon said.
“The results of the OPTIMA study provide valuable insights about the safety and efficacy of Opsumit in combination with a PDE5 inhibitor [Adcirca], and add to the body of evidence supporting combination therapy as the standard of care,” concluded Alessandro Maresta, MD, vice president and head of medical affairs at Actelion.