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-naive 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-B 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.

TABLE OF CONTENTS

CONTENTS

OVERVIEW

DISEASE BACKGROUND

• Definition
• Etiology
• Symptoms
• Diagnosis and testing
• Risk factors
• Patient segmentation
• Genetics

TREATMENT

• Drug classes
• Treatment guidelines

EPIDEMIOLOGY

• Prevalence methodology

MARKETED DRUGS

PIPELINE DRUGS

KEY REGULATORY EVENTS

• Keeping Track Of US FDA Decisions: Approvals For Ongentys And New Keytruda, Darzalex Dosing, But Not For Trevyent
• Keeping Track: US FDA Approves Koselugo, Bestows BTDs on Bavencio, Sotatercept
• United Files Trevyent Following Design Verification Testing

PROBABILITY OF SUCCESS

LICENSING AND ASSET ACQUISITION DEALS

• $3bn Roivant Deal To Fill Holes At Dainippon

CLINICAL TRIAL LANDSCAPE

• Sponsors by status
• Sponsors by phase
• Recent events

DRUG ASSESSMENT MODEL

• ERAs
• PDE5 inhibitors
• Guanyl cyclase stimulator
• Prostacyclin analogs and agonists
• Pipeline candidates

MARKET DYNAMICS

FUTURE TRENDS

• The PH market will continue to grow due to label expansions into non-PAH subtypes
• Positive data on morbidity/mortality endpoints will increase uptake of drugs
• Prostacyclins will be the most lucrative drug class
• Johnson & Johnson will boast both market leaders
• Pipeline candidates will diversify the market and introduce improved delivery systems

CONSENSUS FORECASTS

RECENT EVENTS AND ANALYST OPINION

• Simdax for PAH and PH (June 2, 2020)
• Tyvaso for PAH and PH (February 24, 2020)
• Sotatercept for PAH and PH (January 27, 2020)
• Revatio for PH and PAH (June 28, 2019)
• LIQ861 for PH and PAH (June 28, 2019)
• Opsumit for PAH and PH (June 25, 2019)
• Udenafil for PAH and PH (June 25, 2019)
• Beraprost 314d for PH and PAH (April 8, 2019)
• INOpulse for PH and PAH (January 7, 2019)

KEY UPCOMING EVENTS

UNMET NEEDS

BIBLIOGRAPHY

• Prescription Information:

APPENDIX

LIST OF FIGURES

• Figure 1: Trends in prevalent cases of pulmonary arterial hypertension, 2018-27
• Figure 2: Overview of pipeline drugs for pulmonary hypertension in the US
• Figure 3: Pipeline drugs for pulmonary hypertension, by company
• Figure 4: Pipeline drugs for pulmonary hypertension, by drug type
• Figure 5: Pipeline drugs for pulmonary hypertension, by classification
• Figure 6: Probability of success in the pulmonary hypertension pipeline
• Figure 7: Clinical trials in hypertension
• Figure 8: Top 10 drugs for clinical trials in hypertension
• Figure 9: Top 10 companies for clinical trials in hypertension
• Figure 10: Trial locations in hypertension
• Figure 11: Hypertension trials status
• Figure 12: Hypertension trials sponsors, by phase
• Figure 13: Datamonitor Healthcare's drug assessment summary for pulmonary hypertension
• Figure 14: Market dynamics in pulmonary hypertension
• Figure 15: Future trends in pulmonary hypertension
• Figure 16: Simdax for PAH and PH (June 2, 2020)
• Figure 17: Tyvaso for PAH and PH (February 24, 2020): Phase II/III - INCREASE (ILD Patients)
• Figure 18: Sotatercept for PAH and PH (January 27, 2020): Phase II PULSAR
• Figure 19: Revatio for PAH and PH (June 28, 2019): Phase III - Neonates
• Figure 20: Key upcoming events in pulmonary hypertension

LIST OF TABLES

• Table 1: Pulmonary hypertension clinical classification groups
• Table 2: Pulmonary hypertension clinical classification sub-groups
• Table 3: Classification groups by genetic influences
• Table 4: Pulmonary hypertension drug classes
• Table 5: 2019 ACCP guidelines
• Table 6: 2015 ESC/ERA guidelines
• Table 7: Prevalent cases of pulmonary arterial hypertension, 2018-27
• Table 8: Prevalent cases of pulmonary arterial hypertension, by subtype
• Table 9: Prevalent cases of pulmonary arterial hypertension, by NYHA functional class
• Table 10: Marketed drugs for pulmonary hypertension
• Table 11: Pipeline drugs for pulmonary hypertension
• Table 12: Historical global sales, by drug ($m), 2015-19
• Table 13: Forecasted global sales, by drug ($m), 2020-24
• Table 14: Simdax for PAH and PH (June 2, 2020)
• Table 15: Tyvaso for PAH and PH (February 24, 2020)
• Table 16: Sotatercept for PAH and PH (January 27, 2020)
• Table 17: Revatio for PH and PAH (June 28, 2019)
• Table 18: LIQ861 for PH and PAH (June 28, 2019)
• Table 19: Opsumit for PAH and PH (June 25, 2019)
• Table 20: Udenafil for PAH and PH (June 25, 2019)
• Table 21: Beraprost 314d for PH and PAH (April 8, 2019)
• Table 22: INOpulse for PH and PAH (January 7, 2019)