PUBLISHER: DelveInsight | PRODUCT CODE: 1544153
PUBLISHER: DelveInsight | PRODUCT CODE: 1544153
DelveInsight's "Pulmonary Arterial Hypertension - Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of pulmonary arterial hypertension, historical and forecasted epidemiology, as well as the pulmonary arterial hypertension market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
The pulmonary arterial hypertension market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM pulmonary arterial hypertension market size from 2020 to 2034. The report also covers pulmonary arterial hypertension treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.
Study Period: 2020-2034
Pulmonary Arterial Hypertension Overview
Pulmonary arterial hypertension is a rare, progressive disorder characterized by hypertension in the pulmonary arteries for no apparent reason. It was defined by the 6th World Symposium on Pulmonary Hypertension (WSPH) as a resting mean pulmonary artery pressure (mPAP) of 20 mm Hg or greater, a normal end-expiratory pulmonary artery wedge pressure (PAWP) less than or equal to 15 mm Hg, and a PVR of greater than or equal to 3 Wood units.
Pulmonary arterial hypertension is further classified by the WHO into the following types: idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), drug- and toxin-induced pulmonary arterial hypertension, and pulmonary arterial hypertension associated with other diseases and disorders. The associated conditions include cirrhosis, HIV, congenital heart disease, and connective tissue diseases like scleroderma among others.
Pulmonary Arterial Hypertension diagnosis
Symptoms usually go unnoticed and may be present for up to 2 or 3 years before a diagnosis is made, often leading to misdiagnosis or a delay in early-stage diagnosis. While the global guidelines for pulmonary arterial hypertension promote cardiac catheterization as the gold standard for diagnosis, transthoracic echocardiography is the most prevalent method of diagnosis. Electrocardiogram (ECG), chest radiography, pulmonary function tests, and blood tests are also done to determine pulmonary arterial hypertension. With improvement in disease understanding, biomarker-based assay and genetic testing are also being done to ascertain pulmonary arterial hypertension. The Six-Minute Walk Test (6MWT) is also a widely used test to determine a patient's activity tolerance and estimated 1-year mortality.
Further details related to country-based variations are provided in the report...
Pulmonary Arterial Hypertension treatment
The main purpose of the treatment of pulmonary arterial hypertension is to improve patients' symptoms and slow the rate of clinical deterioration. General measures, supportive therapy, pharmacological treatment, and surgical treatment are used for treating pulmonary arterial hypertension.
The current mainstay therapies that include PDE5 inhibitors, sGC stimulators, ERAs, prostacyclin analog, and agonists, for the treatment of pulmonary arterial hypertension, target the three major pathways, NO/cGMP, endothelin, and prostacyclin. The marketed therapies approved for the treatment of pulmonary arterial hypertension across various WHO Functional Classes (FC) include Johnson & Johnson/Nippon Shinyaku's UPTRAVI (selexipag) and OPSUMIT (macitentan), United Therapeutics and Mochida Pharmaceutical's REMODULIN/TREPROST (treprostinil) (IV, SC), TYVASO (treprostinil, Inhaled), United Therapeutics' ORENITRAM (treprostinil), and Bayer/Merck's ADEMPAS (riociguat).
Recently a combination therapy of LETAIRIS/VOLIBRIS (ambrisentan) and ADCIRCA (tadalafil) also received approval. Most of these therapies are approved for adults except sildenafil, though trials are ongoing in the pediatric population for UPTRAVI, ADEMPAS, and OPSUMIT. Janssen Pharmaceuticals is also developing OPSUMIT with tadalafil as a fixed-dose combination formulation.
As the market is derived using a patient-based model, the pulmonary arterial hypertension epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total prevalent cases of pulmonary arterial hypertension, total diagnosed prevalent cases of pulmonary arterial hypertension, age-specific diagnosed prevalent cases of pulmonary arterial hypertension, gender-specific diagnosed prevalent cases of pulmonary arterial hypertension, class-specific diagnosed prevalent cases of pulmonary arterial hypertension, and subtype-specific diagnosed prevalent cases of pulmonary arterial hypertension in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.
The drug chapter segment of the pulmonary arterial hypertension report encloses a detailed analysis of pulmonary arterial hypertension-marketed drugs and mid to late-stage (Phase III and Phase II) pipeline drugs. It also helps understand the pulmonary arterial hypertension clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.
Marketed Drugs
UPTRAVI (selexipag): Johnson & Johnson/Nippon Shinyaku
UPTRAVI (selexipag), developed by Actelion Pharmaceuticals, is a selective prostacyclin receptor agonist structurally distinct from prostacyclin. It is hydrolyzed by carboxylesterase 1 to yield an active metabolite more potent than selexipag.
The prostacyclin receptor is one of the five major types of prostanoid receptors (IP, EP, DP, TP, and FP). In contrast to other prostanoid receptors, selexipag and its active metabolite are both selective for the prostacyclin receptor. In July 2021, the US FDA approved Janssen Pharmaceutical's UPTRAVI (selexipag) injection for IV use for treating pulmonary arterial hypertension (WHO Group I) to delay disease progression and reduce the risk of hospitalization for pulmonary arterial hypertension. In November 2016, Nippon Shinyaku launched UPTRAVI (selexipag) tablets for treating pulmonary arterial hypertension in Japan after approval from MHLW. In May 2016, EC granted Actelion marketing authorization for UPTRAVI (selexipag) tablets for the long-term treatment of pulmonary arterial hypertension in adult patients with WHO FC II-III, either as a combination therapy in patients insufficiently controlled with an ERA and/or a PDE-5 inhibitor or as monotherapy in patients who are not candidates for these therapies and in December 2015, the US FDA granted Actelion Pharmaceuticals approval of UPTRAVI (selexipag) tablets for treating pulmonary arterial hypertension (WHO Group I) to delay disease progression.
Emerging Drugs
Ralinepag: United Therapeutics
Ralinepag is a novel, oral, selective, and potent prostacyclin receptor agonist being developed by United Therapeutics for the treatment of pulmonary arterial hypertension. In vitro studies indicate that ralinepag has high binding affinity and selectivity at the human prostacyclin (IP) receptor.
In phase II studies, ralinepag demonstrated a potential for a once-a-day dosing profile and potentially enhanced affinity compared to selexipag.
United Therapeutics is currently assessing ralinepag in a Phase III ADVANCE OUTCOMES registrational study. It is a global, multicenter, placebo-controlled trial of patients on approved oral background pulmonary arterial hypertension therapies, with data expected by 2025.
In January 2019, ODD was granted by the EC to Arena Pharmaceutical ralinepag for the treatment of pulmonary arterial hypertension. In September 2014, ralinepag was granted ODD for treating pulmonary arterial hypertension by the US FDA.
Drug Class Insights
Current treatment recommendations weigh the use of multiple factors, including WHO FC, exercise ability, lab indices, and hemodynamic and echocardiographic variables to establish the overall severity of the disease and guide the intensity of therapy. Initial therapy choices and subsequent therapy changes are determined to achieve a low-risk category that helps improve overall survival and functional status in pulmonary arterial hypertension.
The four drug classes (PDE5 inhibitors, sGC stimulators, ERAs, prostacyclin analog, and agonists) widely used for treating target three major signaling pathways, prostacyclin, endothelin, and nitric oxide, are responsible for pulmonary arterial hypertension. Various therapies are approved for the treatment of pulmonary arterial hypertension across FCs like UPTRAVI (selexipag), REMODULIN (treprostinil) (IV, SC), TYVASO (treprostinil, inhaled), ADEMPAS (riociguat), OPSUMIT (macitentan), and ORENITRAM (treprostinil). These are currently available in the market.
These approved therapies target the three major pathways. Medications targeting the NO pathway include PDE5i (sildenafil and tadalafil) and the sGC stimulator (riociguat). PDE5 inhibitors prevent cGMP breakdown, while riociguat acts through direct stimulation of sGC, which produces cGMP. cGMP activates protein kinase G, lowering intracellular Ca2+ concentrations and producing smooth muscle relaxation and vasodilatation. In recent years, riociguat has received focus, given its potential as a substitution for PDE5 inhibitors in patients not meeting treatment targets. The RESPITE study in 61 WHO FC III pulmonary arterial hypertension patients that substituted riociguat for PDE5 inhibitors showed an increase in 6MWD of 31 +/- 63 m by 24 weeks (p = 0.001), alongside statistically significant reductions in nt-pro-BNP level and pulmonary vascular resistance. This data was followed up on with the REPLACE trial. Together these studies demonstrated switching from PDE5 inhibitors to riociguat as a promising option for pulmonary arterial hypertension patients who have failed to progress to low-risk status on their current therapies.
Current primary treatments for pulmonary arterial hypertension focus on widening the pulmonary blood vessels, which reduces resistance in the lungs and consequently enhances the function of the right ventricle, leading to improvements in functional ability. The overarching objective of treatment is to enhance survival, quality of life, exercise capacity, symptom management, and overall clinical outcomes. Risk assessment tools are increasingly utilized to tailor therapy, aiming to optimize these aspects of patient care.
Current treatment guidelines consider various factors such as World Health Organization Functional Class (WHO FC), exercise capacity, laboratory findings, as well as hemodynamic and echocardiographic assessments to assess the severity of pulmonary arterial hypertension and tailor treatment accordingly. The selection of initial therapy and adjustments thereafter aim to achieve a low-risk categorization, which in turn contributes to enhancing both survival rates and functional status in individuals with pulmonary arterial hypertension.
Despite all the advances made over the last few decades with treatment modalities, pulmonary arterial hypertension is still a devastating, rapidly progressive disease with mortality. There is a need for curative therapy, an alternative to the current treatment of multiple injections of medication per week, often associated with injection-site reactions, to maintain their health. Various drugs are being developed that are highly selective and potent, like ralinepag, with in vitro data suggesting more potent antiproliferative and vasodilatory properties. Agents targeting immune pathways, DNA repair, cellular senescence, and metabolic pathways are also in the early stages of development. Thus the pipeline for pulmonary arterial hypertension is robust and dynamic and is expected to create a tectonic impact on the existing market scenario during the forecast period (2023-2034).
Continued in report...
The current market segmentation is based on the therapies prescribed. The drugs that are being used in the present market include UPTRAVI (selexipag), REMODULIN/TREPROST (treprostinil) (IV, SC, Inhalation), TYVASO (treprostinil, Inhaled), ADEMPAS (riociguat), OPSUMIT (macitentan), and ORENITRAM (treprostinil) is included. These are the major segments covered in the forecast model.
Several key players are evaluating their lead candidates in different stages of clinical development like Ralinepag by United Therapeutics.
The market for pulmonary arterial hypertension is expected to experience positive growth.
This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2020-2034. For example, United Therapeutics' Ralinepag, an oral, selective, and potent prostacyclin receptor agonist, is projected to enter the US market in 2025 with a "medium" uptake.
Further detailed analysis of emerging therapies drug uptake in the report...
Pulmonary Arterial Hypertension Pipeline Development Activities
The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics.
Pipeline development activities
The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for emerging therapies for Pulmonary Arterial Hypertension.
KOL Views
To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on pulmonary arterial hypertension evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including Medical/scientific writers, Medical Professionals, Professors, Directors, and Others.
DelveInsight's analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers like the University of Pennsylvania Hospital, Philadelphia, University of Chicago, Chicago, Medizinische Hochschule Hannover, Hannover, Hopital Marie Lannelongue, Le Plessis-Robinson, and Osaka University Hospital, Osaka were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or pulmonary arterial hypertension market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.
Physician's View
According to our primary research analysis, despite significant advancements in the treatment of pulmonary arterial hypertension, there remains a notable unmet need to effectively manage this complex condition. One of the primary challenges lies in the progressive nature of pulmonary arterial hypertension, where many patients continue to experience disease progression despite available therapies. While current treatments primarily target vasodilation and improving right ventricular function, they often do not address underlying pathophysiological mechanisms such as endothelial dysfunction, inflammation, and abnormal cell proliferation. Additionally, there is a lack of curative therapies, and existing treatments may only delay disease progression rather than halt or reverse it entirely. Furthermore, the heterogeneity of pulmonary arterial hypertension presents a challenge in identifying the most effective treatment approach for individual patients. Novel therapies that target alternative pathways, address underlying mechanisms, and provide personalized treatment options are needed to improve outcomes, prolong survival, and enhance the quality of life for individuals living with pulmonary arterial hypertension. Additionally, there is a need for better risk stratification tools and biomarkers to identify patients who are at higher risk of disease progression and may benefit from more aggressive treatment strategies.
According to a KOL in the US, nearly half of the pulmonary arterial hypertension cases are idiopathic, hereditary, or anorexigenic-induced pulmonary arterial hypertension. Women between the ages of 30 and 60 are typically affected by pulmonary arterial hypertension. However, it may occur in men and is frequently linked to worse clinical consequences.
As per another KOL, of the genetically predisposed individuals that develop pulmonary arterial hypertension, only 10-20% of people with the underlying mutations develop it because it is inherited as an autosomal dominant characteristic with reduced penetrance.
Another KOL found that parenteral prostacyclins like treprostinil administered subcutaneously, or epoprostenol, administered intravenously, are the most effective prostacyclins in France. These drugs are administered as 24-hour pumps connected to a vein or subcutaneous perfusion; less than 5% of oral prostacyclins are used.
Qualitative Analysis
We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.
Conjoint Analysis analyzes multiple emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.
In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance number of subjects with treatment-emergent adverse events [Safety and Tolerability], and others.
Further, the therapies' safety is evaluated wherein the adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials, which directly affects the safety of the molecule in the upcoming trials. It sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.
Market Access and Reimbursement
The high cost of therapies for the treatment is a major factor restraining the growth of the drug market. Because of the high cost, the economic burden is increasing, leading the patient to escape from proper treatment.
The reimbursement challenges related to medical care and treatment for individuals with pulmonary arterial hypertension can be significant as it often requires specialized medical attention, covering the costs of diagnosis, treatment, and ongoing care. Health insurance plans may not fully cover limited coverage of some medical treatments, and therapies specific to pulmonary arterial hypertension. This can result in high out-of-pocket expenses for families seeking the best care for their loved ones. Moreover, it requires specialized care from healthcare providers with expertise. Finding and accessing such specialists may be challenging, and the associated costs may not always be fully reimbursed by insurance.
Further details will be provided in the report.
The report provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenarios, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.
Market Insights
Epidemiology Insights
Current Treatment Scenario, Marketed Drugs, and Emerging Therapies