Pulmonary Arterial Hypertension Market and Forecast Analysis to 2025

Disease Overview

Pulmonary arterial hypertension is one of a group of rare and life-threatening diseases collectively known as pulmonary hypertension (PH). Each PH subgroup shares similar pathophysiology, clinical presentation, and therapeutic approaches. The diseases are characterized by abnormal vascular proliferation and remodeling of the small pulmonary arteries and arterioles, vasoconstriction, and in situ thrombosis. This leads to increased pulmonary arterial pressure and localized hypertension, which can eventually result in heart failure.

Report Highlights

• Datamonitor Healthcare estimates that in 2018, there were approximately 218,500 prevalent cases of pulmonary arterial hypertension (PAH) in individuals of all ages worldwide, and forecasts that number to increase to 241,800 prevalent cases by 2027.
• Datamonitor Healthcare expects the pulmonary hypertension (PH) market to expand over the forecast period due to the approvals of novel therapies, label expansions into non-PAH subtypes, FDA clearance of specialist devices, increased trials demonstrating improved morbidity/mortality data for marketed brands, and a shift to early implementation of triple-combination therapy.
• Current treatments are solely symptomatic and function by targeting three pathways controlling vasodilation, namely the endothelin, nitric oxide, and prostacyclin pathways. For World Health Organization Functional Classification (WHO FC) II and III treatment-naïve patients, dual-combination therapy with endothelin receptor agonists (ERAs) and phosphodiesterase 5 inhibitors (PDE5is) is the first-line treatment strategy, while monotherapy with a prostacyclin is a first-line therapy for WHO FC IV patients, with ERAs and PDE5is positioned as add-ons. However, the prostacyclin class is expected to extend its reach to WHO FC II and III patients following the results of Actelion’s TRITON study, which is investigating the use of a triple combination of Opsumit (ERA), Adcirca (PDE5i), and Uptravi (prostacyclin). If TRITON yields positive data, this will allow prostacyclins to build upon the prevailing trend towards early implementation of polytherapy, which was first established through the AMBITION trial with the dual combination of an ERA and a PDE5i. Additionally, this will markedly expand the prostacyclin class’s potential by encouraging first-line uptake alongside Opsumit, which is a market leader.
• Historically, ERAs have been the most commercially lucrative class; however, in 2019, prostacyclins succeeded them, with total sales of $2,675m versus $2,286m for ERAs. Datamonitor Healthcare anticipates that the gap between prostacyclins and ERAs will widen further over the forecast period because ERAs will be under increased threat both from generics and from the expansion of the use of prostacyclins into triple-combination therapies.
• The PDE5i class, which traditionally held a significant portion of market share, has faced fierce generic competition, with both Adcirca and Revatio being subject to generic erosion in 2018. A loss of market share held by PDE5is, from $817m in 2018 to $301m in 2019, was largely attributable to this generic competition.
• The guanylyl cyclase stimulator class, which consists of a single asset, Adempas, is holding steady by stealing market share from the PDE5i class.
• Johnson & Johnson’s two newer marketed brands, Opsumit and Uptravi, are projected to become the highest-selling products during the forecast period. Opsumit is the established market leader, with blockbuster sales of $1,327m in 2019. These two products will experience strong uptake, benefiting from physician familiarity, a strong position in the treatment guidelines, and robust efficacy data to support them. Importantly, Johnson & Johnson has generated efficacy data for morbidity/mortality, broadening the evidence base for its products. Furthermore, the company is assessing both drugs in combination with Adcirca in the TRITON trial. This will significantly boost sales as Uptravi and Opsumit become best-in-class brands in a trifecta approach to treatment.
• Despite PAH patients making up only 20% of the PH population, most therapies are targeted at this group of patients, with off-label use of drugs for group 2–5 PH. The high rate of off-label use highlights a critical unmet need for approved therapies in these indications. Increasing label expansions to include group 2–4 PH subtypes is a key area of interest and will be a major driver of growth in the PH market. Market leaders Opsumit and Uptravi are being investigated in clinical trials to potentially support label expansions to chronic thromboembolic pulmonary hypertension (CTEPH). This will bring new treatment options to underserved CTEPH patients who currently only have one approved therapy option, Adempas. United Therapeutics is set to submit a filing for the label expansion of the injectable prostacyclin, Tyvaso, to include group 3 PH patients, which will make it the first approved therapy for this subtype, while pipeline candidates bardoxolone methyl and INOpulse are also being developed for the treatment of this subgroup of patients. Given the scarcity of competitors in non-PAH segments, there is a prominent opportunity for market penetration for these drugs.
• The approval of pipeline candidates will diversify the PH market and will meet an important unmet need of therapies to treat the underlying pathophysiology of the disease rather than just disease symptoms. Of the pipeline candidates in late-stage development, bardoxolone methyl and sotatercept target nuclear factor-kappa B (NF-κB) and transforming growth factor beta TGF-β pathways to correct the underlying cause of the disease.
• Other notable pipeline candidates include novel delivery systems such as INOpulse and Trevyent, which are set to revolutionize the delivery of nitric oxide and Remodulin. However, pipeline candidates will have an initially muted effect on the market due to strong physician familiarity with the established drug classes and the static nature of the PH market.