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24-Oct-2019

New OPSUMIT® (macitentan) Data Show Initial Combination Therapy with Tadalafil Improved Haemodynamic Clinical and Functional Parameters in Patients with Pulmonary Arterial Hypertension

Macitentan, as part of a combination regimen, reduced the primary endpoint of mean pulmonary vascular resistance by 47% at week 16 compared with baseline 

[ALLSCHWIL, Switzerland] – October 21, 2019 – Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson, today announces new data evaluating initial combination therapy with OPSUMIT® (macitentan) and tadalafil, a PDE-5 inhibitor. Patients with pulmonary arterial hypertension (PAH, WHO Classification Group 1) taking this combination showed haemodynamic improvement, as well as improvements in functional parameters and risk profiles. The combination was also well tolerated in these patients. The study data is being shared today at the CHEST Annual Meeting 2019 held October 19-23 in New Orleans, Louisiana.

The OPTIMA (cOmbination theraPy of maciTentan and tadalafIl in patients with newly diagnosed pulMonary Arterial Hypertension) study was a prospective, multicentre, single-arm, open-label, Phase IV trial evaluating the efficacy, safety, and tolerability of initial oral combination therapy with macitentan and tadalafil in patients with newly diagnosed PAH. A total of 46 patients were enrolled in the study.1

“Macitentan, 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,” said Olivier Sitbon, M.D., Ph.D., principal investigator and professor of respiratory medicine at Université Paris-Sud. “These data are meaningful because improvement of PVR, an important indicator of right ventricular function, is a key treatment goal. 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.”

Safety and tolerability findings were consistent with previous clinical trials that supported the approval and use of macitentan 10mg once-daily. The most common adverse events (AEs) in the OPTIMA study were peripheral oedema (28.3%), headache (23.9%),

diarrhoea (19.6%), dyspnea (15.2%), anaemia (13.0%) and asthenia (13.0%). Four patients had a decrease in haemoglobin below 10 g/dL and one patient had aminotransferases ≥3 times the upper limit of normal. Three patients discontinued treatment due to AEs and three patients died during the study. Causes of death were cardiac arrest, heart failure, and multiorgan failure with sepsis.1

PAH is a specific form of pulmonary hypertension (PH) in which the walls of the pulmonary arteries (blood vessels leading from the right side of the heart to the lungs) become thick and stiff, narrowing the space for blood to flow, which increases blood pressure.2,3 Despite recent advances, PAH is a serious, progressive disease with no cure, and around one in three patients die within five years of diagnosis.4,5 Risk assessment in PAH is an important tool for monitoring disease progression and response to therapy. The main treatment goal is to achieve and maintain low-risk status.6

“The results of the OPTIMA study provide valuable insights about the safety and efficacy of macitentan in combination with a PDE-5 inhibitor and add to the body of evidence supporting combination therapy as the standard of care,” said Alessandro Maresta, M.D., Vice President and Head of Medical Affairs at Actelion Pharmaceuticals Ltd. “PAH continues to have a devastating impact on people’s lives and our focus is on researching and developing innovative medicines that improve the lives of these patients.”

Macitentan is indicated for the treatment of PAH (WHO Group I) to reduce the risks of disease progression and hospitalisation for PAH. Disease progression included death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). Macitentan also reduced hospitalisation for PAH.7

* Dr. Sitbon has received research support from Actelion and has served as a paid consultant to the company.

About Macitentan

Macitentan is an oral endothelin receptor antagonist (ERA) approved by the European Medicine Agency (EMA) as monotherapy or in combination for the long-term treatment of PAH in adult patients of WHO Functional Class (FC) II to III.7

The effectiveness of macitentan was established in a long-term study in PAH patients with predominantly WHO FC II-III symptoms treated for an average of two years. Patients were treated with macitentan monotherapy or in combination with PDE-5 inhibitors or inhaled prostanoids. Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.7

Macitentan is very likely to cause major birth defects. In both the US and Europe, it is contraindicated for use in pregnancy. In Europe, contraindications for macitentan also include patients with severe hepatic impairment and those with elevated aminotransferase levels three times upper limit of normal; it is also not recommended in patients with moderate hepatic impairment. Liver enzyme tests should be obtained prior to initiation macitentan. Patients should be monitored for signs of hepatic injury and monthly monitoring of ALT and AST is recommended.7

Important Safety Information

For complete European Union (EU) prescribing information, please visit:

https://www.ema.europa.eu/en/documents/product-information/opsumit-epar-product-information_en.pdf

About Pulmonary Arterial Hypertension

PAH is a specific form of PH that causes the walls of the pulmonary arteries (blood vessels leading from the right side of the heart to the lungs) to become thick and stiff, narrowing the space for blood to flow, and causing an increased blood pressure to develop within the lungs. PAH is a serious, progressive disease with a variety of aetiologies, and has a major impact on patients' functioning, as well as their physical, psychological and social wellbeing. There is currently no cure for PH and it is often fatal.4,8,9 Innovative medicines have contributed to the improvement in prognosis for people with PAH, with the median survival time more than doubling over the past two decades – now more than seven years with treatment.4,10

About the OPTIMA Study

OPTIMA was a prospective, multicentre, single-arm, open-label, Phase IV trial evaluating the efficacy, safety and tolerability of initial oral combination therapy with macitentan and tadalafil in patients with newly diagnosed PAH. A total of 46 patients were enrolled and treated (all 46 are included in the efficacy and safety analyses). In the OPTIMA study, the primary endpoint of mean PVR was reduced by 47% at week 16 compared with baseline in newly diagnosed patients with pulmonary arterial hypertension (geometric mean of the ratio week 16 to baseline 0.53; 95% CI 0.47, 0.59). Results showed haemodynamic improvement, as well as improvements in functional parameters including 6-minute walk distance, and risk profile. Safety and tolerability findings were consistent with previous clinical trials that supported the approval and use of macitentan 10 mg once-daily.1

About Actelion

In June 2017, Actelion became part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Actelion's medicines have helped to expand and strengthen Janssen's portfolio with leading, differentiated in-market medicines and promising late-stage compounds. Janssen has added Pulmonary Hypertension as a therapeutic area of focus to maintain the leadership position Actelion has built in this important disease area. Learn more at www.actelion.com. Follow us on Twitter @actelion_com.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology and Pulmonary Hypertension. Learn more at www.janssen.com/emea/Follow us at www.twitter.com/JanssenEMEA. Actelion Pharmaceuticals Ltd is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Follow Actelion on Twitter @actelion_com. 

References

1 Sitbon O, et al. CHEST Annual Meeting 2019: abstract # TBC.

2 McLaughlin VV, et al. J Am Coll Cardiol. 2009; 119(16):2250-94.

3 Schermuly RT, et al. Nat Rev Cardiol 2011; 8(8):443-55.

4 Vachiéry JL and Gaine S. Eur Respir Rev 2012; 21:313-20.

5 Hoeper MM, et al. Eur Respir J 2017; 50:1700740.

6 Raina A, et al. Eur Respir Rev. 2016; 25: 390-398

7 Opsumit Summary of Product Characteristics. Available at

https://www.ema.europa.eu/en/documents/product-information/opsumit-epar- product-information_en.pdf Last accessed October 2019.

8 Galiè N, et al. Eur Heart J 2016; 37:67–119.

9 Hoeper MG, Gibbs SR. Eur Respir Rev 2014; 23:

Editor Details

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Last Updated: 24-Oct-2019