While the primary endpoint was not met,
exploratory analysis suggests a signal of reduced risk of disease
progression of initial triple oral combination therapy vs initial
double oral therapy for Pulmonary Arterial Hypertension (PAH)
patients
Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company
of Johnson & Johnson, today announced results from the Phase 3b
TRITON trial, the first randomised controlled study evaluating the
efficacy and safety of initial triple oral combination therapy
(UPTRAVI® [selexipag], OPSUMIT® [macitentan] and tadalafil)
compared to initial double oral combination therapy (placebo,
macitentan and tadalafil) in newly diagnosed, treatment-naïve
patients with pulmonary arterial hypertension (PAH). Study results
were featured as an oral presentation as part of the digital
European Society of Cardiology Congress held 29 August – 1
September 2020.
In the TRITON trial, both the initial triple oral therapy and
initial double oral therapy arms demonstrated reductions in the
primary endpoint, pulmonary vascular resistance, of 54 percent and
52 percent respectively, with no statistical difference observed
between both groups.1 Improvements were observed in six-minute walk
distance,1 N-terminal pro-brain natriuretic peptide (NT-proBNP) and
clinical variables at week 26 in patients who were treated with
either initial triple oral or initial double oral combination
therapy, with no difference between treatment regimens.2
However, initial triple oral therapy was associated with a 41
percent reduction in the risk of first disease progression event
compared to initial oral double therapy at an average follow up of
77.6 and 75.8 weeks, respectively.1 Sixteen initial disease
progression events were observed in patients taking initial triple
oral therapy, and 27 events were observed in patients taking
initial double oral therapy (hazard ratio 0.59; 95 percent
confidence interval [CI]; 0.32, 1.09).3 Two patients died in the
initial triple therapy group (1.7 percent) compared to nine (7.1
percent) in the initial double therapy group up to the end of the
main observation period (hazard ratio 0.23; 95 percent CI 0.05,
1.04). These results are not statistically significant and should
be interpreted as exploratory considering the primary endpoint was
not met.1,3
The nature of reported adverse events (AEs) were consistent with
the known safety profiles of the study medications.1,4,5
“While the study’s primary endpoint was not met, we observed a
signal of reduced risk of disease progression in the initial triple
oral combination therapy group as compared to the initial double
oral therapy group,” said Nazzareno Galiè*, Full Professor of
Cardiology at the Department of Experimental, Diagnostic and
Specialty Medicine (DIMES) of the UNIBO. “This signal requires
further evaluation to enhance our knowledge in the PAH field.”
The efficacy and safety of selexipag has been demonstrated in
PAH previously in the pivotal GRIPHON trial, which showed that,
compared with placebo, selexipag demonstrated a 40 percent risk
reduction in disease progression as captured by the primary
composite end point of morbidity and mortality.4,6 Consistent
results were seen when selexipag was added to double oral therapy
(an endothelin receptor antagonist [ERA] plus a phosphodiesterase
type-5 inhibitor [PDE-5i]), compared to double oral therapy
alone.7
“Data from the TRITON and pivotal GRIPHON studies reinforce the
role of selexipag in the escalation of therapy on top of double
oral therapy with an ERA and PDE-5i. These studies reaffirm
Janssen’s commitment to innovation and the scientific advancement
of PAH treatment and care,” said Alessandro Maresta, M.D., Vice
President and Head of Medical Affairs at Actelion Pharmaceuticals
Ltd, a Janssen Pharmaceutical Company of Johnson & Johnson. “We
will continue to invest in the science and remain committed to
transforming PAH into a long-term, manageable condition so that
patients can live a normal life.”
END
* Prof. Galiè has received research support from Actelion and
has served as a paid consultant to the company. Prof. Galiè is not
being paid by Actelion for media opportunities.
About the TRITON Study1,2,3 TRITON (NCT02558231) is
a multicentre, double-blind, placebo-controlled, Phase 3b study,
that randomised 1:1 newly diagnosed, treatment-naïve, PAH patients
to initial triple oral or initial double oral combination therapy.
Macitentan and tadalafil were initiated at randomisation,
selexipag/placebo at day 15 (uptitrated until week 12). Efficacy
and safety were assessed in a blinded manner and all patients were
followed until the end of the observation period (until the last
patient randomised completed the week 26 visit; median follow-up
time approximately 17 months). The primary endpoint was change in
PVR at week 26, expressed as ratio of baseline. Secondary
endpoints, tested hierarchically, included change in six-minute
walk distance and NT-proBNP at week 26, time to disease progression
(centrally adjudicated) from randomisation until the end of
observation period plus seven days, and absence of worsening WHO
functional class at week 26. Safety was reported up to end of
observation period. The trial enrolled 247 patients.
About Selexipag Selexipag is an oral selective
prostacyclin IP receptor agonist approved by the European Medicines
Agency (EMA) for the long-term treatment of PAH in adult patients
with WHO functional class (FC) II–III, either as combination
therapy in patients insufficiently controlled with an endothelin
receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5)
inhibitor, or as monotherapy in patients who are not candidates for
these therapies. Selexipag, originally discovered and synthesised
by Nippon Shinyaku, is the only globally-available oral treatment
that works on the prostacyclin pathway with evidence of long-term
outcomes.4
The efficacy of selexipag in PAH was established in GRIPHON
(Prostacyclin (PGI2) Receptor agonist In
Pulmonary arterial HypertensiON), the largest
randomised, controlled trial ever conducted in PAH patients. This
double-blind, multicentre study aimed to evaluate the long-term
efficacy and safety of oral selexipag and included almost 400
patients who were already receiving double combination PAH
treatment. The study provided the first randomised, controlled
evidence for triple oral combination therapy in PAH. Selexipag was
shown to delay disease progression and significantly reduce the
risk of hospitalisation compared with placebo, as well as improving
exercise capacity.6 Overall, the most common adverse events in the
selexipag group were consistent with the known side effects of
prostacyclin, including headache, diarrhoea, nausea, and jaw
pain.6
Important Safety Information For complete
prescribing information, please visit: https://www.ema.europa.eu/en/documents/product-information/uptravi-epar-product-information_en.pdf
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.5
The efficacy of macitentan in PAH was established in SERAPHIN
(Study with an Endothelin Receptor
Antagonist in Pulmonary arterial Hypertension
to Improve cliNical outcome), a long-term
event-driven study in PAH patients with predominantly WHO FC II-III
symptoms treated for an average of two years.5 SERAPHIN was the
largest and longest clinical study conducted at that time, and the
first completed study that demonstrated long-term outcomes with a
composite morbidity and mortality primary endpoint.5,8 Compared
with placebo, macitentan significantly reduced the risk of the
first occurrence of a morbidity or mortality event (the primary
endpoint).5 Macitentan also reduced the risk of PAH-related death
and hospitalisation, as well as significantly improving WHO FC and
health-related quality of life versus placebo.9,10 Overall, the
most common adverse events frequently associated with macitentan
than placebo were headache, nasopharyngitis and anaemia.11
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) PAH is
a specific form of pulmonary hypertension (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.12,13,14 However, the last decade has seen
significant advances in the understanding of the pathophysiology of
PAH, transforming the prognosis for PAH patients from symptomatic
improvements in exercise tolerance 10 years ago, to delayed disease
progression today.
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.
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 https://www.janssen.com/emea/. Follow
us at https://twitter.com/janssenemea. Actelion Pharmaceuticals Ltd
is one of the Janssen Pharmaceutical Companies of Johnson &
Johnson. Follow Actelion on Twitter @actelion_com.
Cautions Concerning Forward-looking Statements This
press release contains "forward-looking statements" as defined in
the Private Securities Litigation Reform Act of 1995 regarding
UPTRAVI® (selexipag) and OPSUMIT® (macitentan). The reader is
cautioned not to rely on these forward-looking statements. These
statements are based on current expectations of future events. If
underlying assumptions prove inaccurate or known or unknown risks
or uncertainties materialise, actual results could vary materially
from the expectations and projections of Actelion Pharmaceuticals
Ltd, any of the other Janssen Pharmaceutical Companies and/or
Johnson & Johnson. Risks and uncertainties include, but are not
limited to: challenges and uncertainties inherent in product
research and development, including the uncertainty of clinical
success and of obtaining regulatory approvals; uncertainty of
commercial success; manufacturing difficulties and delays;
competition, including technological advances, new products and
patents attained by competitors; challenges to patents; product
efficacy or safety concerns resulting in product recalls or
regulatory action; changes in behaviour and spending patterns of
purchasers of health care products and services; changes to
applicable laws and regulations, including global health care
reforms; and trends toward health care cost containment. A further
list and descriptions of these risks, uncertainties and other
factors can be found in Johnson & Johnson's Annual Report on
Form 10-K for the fiscal year ended December 29, 2019, including in
the sections captioned "Cautionary Note Regarding Forward-Looking
Statements" and "Item 1A. Risk Factors,” and in the company's most
recently filed Quarterly Report on Form 10-Q, and the company's
subsequent filings with the Securities and Exchange Commission.
Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson &
Johnson. None of the Janssen Pharmaceutical Companies nor Johnson
& Johnson undertakes to update any forward-looking statement as
a result of new information or future events or developments.
# # #
References
- Galié N, et al. Long-term outcomes in newly diagnosed pulmonary
arterial hypertension (PAH) patients receiving initial triple oral
combination therapy: Insights from the randomised controlled TRITON
study. European Society of Cardiology Congress. 31 August – 1
September 2020. Virtual.
- Chin K, et al. Efficacy and Safety of Initial Triple Oral
Versus Initial Double Oral Combination Therapy in Patients with
Newly Diagnosed Pulmonary Arterial Hypertension (PAH): Results of
the Randomized Controlled TRITON Study. Am J Respir Crit Care Med
2020;201:A2928.
- Galié, N. Long-term outcomes in newly diagnosed pulmonary
arterial hypertension (PAH) patients receiving initial triple oral
combination therapy: Insights from the randomised controlled TRITON
study. Presented at European Society of Cardiology Congress. 29
August – 1 September 2020. Virtual.
- UPTRAVI® (selexipag) Summary of Product Characteristics.
Janssen-Cilag International NV. July 2019.
- OPSUMIT® (macitentan) Summary of Product Characteristics.
Janssen-Cilag International NV. April 2020.
- Sitbon O, et al. Selexipag for the Treatment of Pulmonary
Arterial Hypertension. N Engl J Med2015;373(26):2522–33.
- Coghlan J, et al. Targeting the Prostacyclin Pathway with
Selexipag in Patients with Pulmonary Arterial Hypertension
Receiving Double Combination Therapy: Insights from the Randomized
Controlled GRIPHON Study. Am J Cardiovasc Drugs 2018; 18:
37–47.
- Said, K. Macitentan in pulmonary arterial hypertension: The
SERAPHIN trial. Glob Cardiol Sci Pract 2014; 2:26–30.
- Channick RN, et al. Effect of Macitentan on Hospitalizations.
Results from the SERAPHIN Trial. JACC Heart Fail 2015; 3:1-8.
- Mehta S, et al. Macitentan Improves Health-Related Quality of
Life for Patients With Pulmonary Arterial Hypertension. Results
From the Randomized Controlled SERAPHIN Trial. Chest 2017;
151:106-18.
- Pulido T, et al. Macitentan and Morbidity and Mortality in
Pulmonary Arterial Hypertension. N Engl J Med 2013;
369:809-18.
- Vachiéry JL, et al. Challenges in the diagnosis and treatment
of pulmonary arterial hypertension.Eur Respir Rev2012;
21:313-20.
- Galiè N, et al. 2015 ESC/ERS Guidelines for the diagnosis and
treatment of pulmonary hypertension.Eur Heart J2016;37:67-119.
- Hoeper MG, et al. The changing landscape of pulmonary arterial
hypertension and implications for patient care. Eur Respir Rev
2014; 23:450-7.
CP-168836 August 2020
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200829005001/en/
Media contacts: Sarah Smith
Mobile: +44 7920 082012 SSmith49@its.jnj.com
David Keown Mobile: +44 7973 824614 Dkeown@its.jnj.com
Investor contact: Jen
McIntyre Office: +1 732-524-3922 JMcInty3@its.jnj.com
Johnson and Johnson (NYSE:JNJ)
Historical Stock Chart
From Mar 2024 to Apr 2024
Johnson and Johnson (NYSE:JNJ)
Historical Stock Chart
From Apr 2023 to Apr 2024