CLINICAL TRIALS PROFILE FOR ADCIRCA

All Clinical Trials for ADCIRCA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01042158 ↗	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	Eli Lilly and Company	Phase 4	2010-01-01	This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Standard outcome measures such as six-minute walk distance (6MWD), New York heart Association (NYHA) classification, and hemodynamic measurements will be assessed, as well as novel functional measures of RV-PV function including the transthoracic echocardiogram parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI and heart rate variability assessed by Holter monitoring. This design (excluding a placebo arm) was selected for ethical concerns and to provide optimal efficiency and active therapy to all study subjects. It also allows for comparisons between the two monotherapies and with combination therapy.
NCT01042158 ↗	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	Johns Hopkins University	Phase 4	2010-01-01	This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Standard outcome measures such as six-minute walk distance (6MWD), New York heart Association (NYHA) classification, and hemodynamic measurements will be assessed, as well as novel functional measures of RV-PV function including the transthoracic echocardiogram parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI and heart rate variability assessed by Holter monitoring. This design (excluding a placebo arm) was selected for ethical concerns and to provide optimal efficiency and active therapy to all study subjects. It also allows for comparisons between the two monotherapies and with combination therapy.
NCT01042158 ↗	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 4	2010-01-01	This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Standard outcome measures such as six-minute walk distance (6MWD), New York heart Association (NYHA) classification, and hemodynamic measurements will be assessed, as well as novel functional measures of RV-PV function including the transthoracic echocardiogram parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI and heart rate variability assessed by Holter monitoring. This design (excluding a placebo arm) was selected for ethical concerns and to provide optimal efficiency and active therapy to all study subjects. It also allows for comparisons between the two monotherapies and with combination therapy.
NCT01042158 ↗	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	National Institutes of Health (NIH)	Phase 4	2010-01-01	This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Standard outcome measures such as six-minute walk distance (6MWD), New York heart Association (NYHA) classification, and hemodynamic measurements will be assessed, as well as novel functional measures of RV-PV function including the transthoracic echocardiogram parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI and heart rate variability assessed by Holter monitoring. This design (excluding a placebo arm) was selected for ethical concerns and to provide optimal efficiency and active therapy to all study subjects. It also allows for comparisons between the two monotherapies and with combination therapy.
NCT01042158 ↗	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	Stanford University	Phase 4	2010-01-01	This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Standard outcome measures such as six-minute walk distance (6MWD), New York heart Association (NYHA) classification, and hemodynamic measurements will be assessed, as well as novel functional measures of RV-PV function including the transthoracic echocardiogram parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI and heart rate variability assessed by Holter monitoring. This design (excluding a placebo arm) was selected for ethical concerns and to provide optimal efficiency and active therapy to all study subjects. It also allows for comparisons between the two monotherapies and with combination therapy.
NCT01042158 ↗	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis	Completed	The Cleveland Clinic	Phase 4	2010-01-01	This will be a 36-week, single group, open label study assessing the effects of Tadalafil plus Ambrisentan combination therapy in patients with pulmonary arterial hypertension associated with the scleroderma spectrum of disease (PAH-SSD). Standard outcome measures such as six-minute walk distance (6MWD), New York heart Association (NYHA) classification, and hemodynamic measurements will be assessed, as well as novel functional measures of RV-PV function including the transthoracic echocardiogram parameter tricuspid annular plane systolic ejection (TAPSE), contrast-enhanced cardiac MRI and heart rate variability assessed by Holter monitoring. This design (excluding a placebo arm) was selected for ethical concerns and to provide optimal efficiency and active therapy to all study subjects. It also allows for comparisons between the two monotherapies and with combination therapy.
NCT00617305 ↗	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)	Completed	Gilead Sciences	Phase 4	2008-04-01	To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy. The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.

Clinical Trial Conditions for ADCIRCA

Condition Name

Condition Name for ADCIRCA
Intervention	Trials
Pulmonary Arterial Hypertension	6
Pulmonary Hypertension	4
Healthy	4
Hypertension, Pulmonary	2

Condition MeSH

Condition MeSH for ADCIRCA
Intervention	Trials
Hypertension	11
Pulmonary Arterial Hypertension	7
Familial Primary Pulmonary Hypertension	7
Hypertension, Pulmonary	7

Clinical Trial Locations for ADCIRCA

Trials by Country

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Trials by Country for ADCIRCA
Location	Trials
United States	71
China	7
Japan	6
Germany	4
Brazil	4

Trials by US State

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−

Trials by US State for ADCIRCA
Location	Trials
California	5
Texas	4
New York	4
Massachusetts	4
Missouri	4

Clinical Trial Progress for ADCIRCA

Clinical Trial Phase

Clinical Trial Phase for ADCIRCA
Clinical Trial Phase	Trials
Phase 4	8
Phase 3	3
Phase 2	2

Clinical Trial Status

Clinical Trial Status for ADCIRCA
Clinical Trial Phase	Trials
Completed	13
Terminated	4
Recruiting	3

Clinical Trial Sponsors for ADCIRCA

Sponsor Name

Sponsor Name for ADCIRCA
Sponsor	Trials
Eli Lilly and Company	4
United Therapeutics	3
Washington University School of Medicine	3

Sponsor Type

Sponsor Type for ADCIRCA
Sponsor	Trials
Other	26
Industry	16
NIH	4

Clinical Trials, Market Analysis, and Projections for ADCIRCA (Tadalafil) in Pulmonary Arterial Hypertension (PAH)

Introduction to ADCIRCA

ADCIRCA, a brand name for the drug tadalafil, is indicated for the treatment of pulmonary arterial hypertension (PAH), specifically WHO Group 1, to improve exercise ability. Here, we will delve into the clinical trials, market analysis, and future projections for this medication.

Clinical Trials and Efficacy

Primary Clinical Trials

ADCIRCA has been extensively studied in clinical trials to establish its efficacy in treating PAH. The PHIRST-1 pivotal trial, for example, demonstrated that ADCIRCA significantly improved the 6-minute walk distance (6MWD) compared to placebo. This improvement was evident as early as 8 weeks and was sustained at weeks 12 and 16[4].

• Monotherapy and Combination Therapy: ADCIRCA showed significant improvements in 6MWD when used as monotherapy and in combination with background bosentan therapy. In the PHIRST-1 trial, 53% of patients were on background therapy with bosentan[4].

• Clinical Worsening: The drug reduced the risk of clinical worsening, defined as death, lung transplantation, atrial septostomy, hospitalization due to worsening PAH, or initiation of new PAH therapies[4].

Long-Term Outcomes

Long-term extension studies have provided valuable insights into the sustained efficacy and safety of ADCIRCA. A median follow-up of 356 days showed a survival rate of 96.5 per 100 patient-years, although these data must be interpreted cautiously due to the lack of a control group[4].

Adverse Events

The most common adverse events associated with ADCIRCA were generally transient and mild to moderate in intensity. These included headache, myalgia, nasopharyngitis, flushing, and respiratory tract infections. Discontinuations due to adverse events were similar to those in the placebo group[1].

Market Analysis

Current Market Landscape

The global PAH market has seen significant shifts in recent years. Historically, endothelin receptor antagonists (ERAs) were the most commercially lucrative class, but in 2019, prostacyclins surpassed them with total sales of $2,675 million compared to $2,286 million for ERAs[2][3].

• Generic Competition: The PDE5 inhibitor (PDE5i) class, which includes ADCIRCA, has faced intense generic competition since 2018. This has led to a significant decline in market share for PDE5is, from $817 million in 2018 to $301 million in 2019[2].

• Emerging Therapies: The guanylyl cyclase stimulator (GCS) class, represented by Adempas, has also been gaining market share, particularly among patients who respond poorly to PDE5is[2].

Market Projections

The PAH market is expected to grow, driven by increasing prevalence and the introduction of new therapies. By 2027, the number of prevalent cases of PAH is forecasted to increase from approximately 218,500 in 2018 to 241,800[2].

• Polytherapy Trends: The trend towards early implementation of polytherapy, first established by the AMBITION trial with the dual combination of an ERA and a PDE5i, is expected to continue. This could further expand the market for prostacyclins and potentially benefit ADCIRCA if larger trials demonstrate significant clinical benefits[2][3].

• Competitive Landscape: Market leaders like Opsumit and Uptravi are being investigated in clinical trials for potential label expansions, which could impact the competitive landscape. However, ADCIRCA's established efficacy and safety profile, along with its use in combination therapies, will likely maintain its position in the market[3].

Future Projections and Challenges

Clinical Trials and Label Expansions

Ongoing and future clinical trials, such as those investigating the use of triple combination therapies, will be crucial in determining the long-term market position of ADCIRCA. If additional larger trials reveal significant clinical benefits, this could support the continued use of ADCIRCA in polytherapy regimens[2][3].

Generic Erosion and Patent Expiry

The impact of generic competition on ADCIRCA's market share is a significant challenge. As patents expire and more generics enter the market, the brand's market share is likely to continue declining unless new indications or combination therapies are approved[2].

Regulatory and Economic Factors

Global and Chinese macroeconomic conditions, as well as regulatory changes, can influence the Adcirca market. Economic factors such as production costs, supply and demand dynamics, and import/export regulations will also play a role in shaping the market's future[5].

Key Takeaways

• Clinical Efficacy: ADCIRCA has demonstrated significant improvements in exercise ability and reduced clinical worsening in PAH patients.
• Market Trends: The PAH market is shifting towards polytherapy, with prostacyclins gaining prominence over ERAs and PDE5is facing generic competition.
• Future Outlook: Ongoing clinical trials and potential label expansions will be critical in determining ADCIRCA's future market position.
• Challenges: Generic erosion and economic factors will continue to impact the market share of ADCIRCA.

FAQs

What is the primary indication for ADCIRCA?

ADCIRCA is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability.

What are the common adverse events associated with ADCIRCA?

Common adverse events include headache, myalgia, nasopharyngitis, flushing, and respiratory tract infections, which are generally transient and mild to moderate in intensity.

How does ADCIRCA perform in combination therapy?

ADCIRCA has been studied and shown to be effective when used in combination with background bosentan therapy, improving 6MWD and reducing clinical worsening.

What is the impact of generic competition on ADCIRCA's market share?

Generic competition has significantly reduced the market share of ADCIRCA, with sales declining from $817 million in 2018 to $301 million in 2019.

What are the future market projections for the PAH treatment landscape?

The PAH market is expected to grow, with a shift towards polytherapy and an increasing prevalence of PAH cases. Prostacyclins are anticipated to continue gaining market share over ERAs and PDE5is.

Sources

1. Eli Lilly: ADCIRCA (tadalafil) tablets [PDF].
2. Business Wire: Global Pulmonary Arterial Hypertension Market and Forecast Analysis to 2025.
3. GlobeNewswire: Global Pulmonary Arterial Hypertension Market Report 2021.
4. ADCIRCA: Efficacy | ADCIRCA (tadalafil) tablets.
5. Prof Research: Adcirca Market Size, Share, Trend and Forecast to 2025.