CLINICAL TRIALS PROFILE FOR FLOLAN

All Clinical Trials for FLOLAN

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00004754 ↗	Phase IV Study of Chronic Infusional Epoprostenol for Severe Primary Pulmonary Hypertension	Completed	Baylor College of Medicine	Phase 4	1993-08-01	OBJECTIVES: I. Provide epoprostenol (Flolan, prostaglandin I2) by chronic infusion to patients with severe primary pulmonary hypertension for whom no alternative therapy is available. II. Obtain additional safety information on continuous infusion epoprostenol. III. Obtain additional information on economic resource health consumption.
NCT00004754 ↗	Phase IV Study of Chronic Infusional Epoprostenol for Severe Primary Pulmonary Hypertension	Completed	National Center for Research Resources (NCRR)	Phase 4	1993-08-01	OBJECTIVES: I. Provide epoprostenol (Flolan, prostaglandin I2) by chronic infusion to patients with severe primary pulmonary hypertension for whom no alternative therapy is available. II. Obtain additional safety information on continuous infusion epoprostenol. III. Obtain additional information on economic resource health consumption.
NCT00058929 ↗	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension	Completed	United Therapeutics	Phase 4	2002-10-01	This trial is a study of Remodulin in patients with pulmonary arterial hypertension who have been transitioned from Flolan therapy. The study consists of Screening, Baseline and Treatment Phases. Patients meeting all inclusion/exclusion criteria during the Screening Phase will enter the Baseline Phase, during which baseline exercise capacity, vital signs, and clinical signs and symptoms of the disease will be assessed. After confirmation of all inclusion/exclusion criteria, patients will be assigned to study drug (Remodulin or placebo) and will enter the Treatment Phase. The Treatment Phase begins with a Dose Transition Period, during which patients will begin receiving subcutaneous study drug at a low dose determined by the patient's current dose of Flolan. The study drug dose will be increased gradually while the Flolan dose is decreased gradually over a period of up to 14 days. The dose changes will continue until Flolan therapy has been discontinued and the patient is stable on study drug. Patients who are transitioned off Flolan, who are stable on study drug will be discharged from the clinic, and will continue to receive study drug on an outpatient basis. The patient will return to the clinic at Weeks 4 and 8 for assessments. Patients will remain on study drug for 8 weeks from the first dose of study drug. At Week 8, final assessments will be conducted and the patient will be dismissed from the study. Patients who successfully complete Week 8 assessments may be offered Remodulin therapy or other therapy, at the investigator's discretion.
NCT00373360 ↗	Safety, Efficacy and Treatment Satisfaction in Patients With PAH Rapidly Switched From Epoprostenol to Remodulin	Completed	United Therapeutics	Phase 4	2006-09-01	The purpose of this 8-week study is to compare the effects of switching from therapy with epoprostenol or Flolan to IV Remodulin. This study will also assess the effect that changing to Remodulin will have on patient satisfaction with their treatment and impact on quality of life.
NCT00439946 ↗	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH	Terminated	United Therapeutics	Phase 4	2007-02-01	The purpose of this 8-week study is to compare the effects of switching from intravenous Flolan to intravenous Remodulin therapy. Remodulin (treprostinil sodium) is an approved therapy for pulmonary arterial hypertension (PAH). Unlike Flolan, Remodulin does not need to be mixed daily and is stable at room temperature, so there is no need for ice packs. In addition, Remodulin is changed every 48hrs, instead of every 12-24 (with ice packs) or every 8 hours (without ice packs) with Flolan. Flolan is given using a type of portable medication pump called the CADD Legacy infusion pump. In this study, Remodulin will be given using a smaller and lighter medication pump called the Crono Five infusion pump. This study will also assess the effect that changing to Remodulin will have on treatment satisfaction and patient quality of life.
NCT00452218 ↗	Sorafenib Study: Dosing in Patients With Pulmonary Arterial Hypertension (PAH)	Completed	Bayer	Phase 1	2007-03-01	The purpose of this study is to assess the safety and tolerability of sorafenib in patients with PAH already on existing therapy with a prostacyclin [epoprostenol (Flolan)], treprostinil (Remodulin), or iloprost alone, or with or without sildenafil (Viagra/Revatio).

Clinical Trial Conditions for FLOLAN

Condition Name

Condition Name for FLOLAN
Intervention	Trials
Pulmonary Arterial Hypertension	6
Hypertension, Pulmonary	3
Cardiovascular Disease	2
Pulmonary Hypertension	2

Condition MeSH

Condition MeSH for FLOLAN
Intervention	Trials
Hypertension	10
Pulmonary Arterial Hypertension	9
Familial Primary Pulmonary Hypertension	8
Hypertension, Pulmonary	5

Clinical Trial Locations for FLOLAN

Trials by Country

Trials by Country for FLOLAN
Location	Trials
United States	31
Canada	4
Netherlands	3
Sweden	1
Italy	1

Trials by US State

Trials by US State for FLOLAN
Location	Trials
Texas	4
California	4
North Carolina	3
Ohio	3
Illinois	3

Clinical Trial Progress for FLOLAN

Clinical Trial Phase

Clinical Trial Phase for FLOLAN
Clinical Trial Phase	Trials
Phase 4	11
Phase 3	1
Phase 2	1

Clinical Trial Status

Clinical Trial Status for FLOLAN
Clinical Trial Phase	Trials
Completed	14
Terminated	2

Clinical Trial Sponsors for FLOLAN

Sponsor Name

Sponsor Name for FLOLAN
Sponsor	Trials
United Therapeutics	4
Actelion	3
GlaxoSmithKline	3

Sponsor Type

Sponsor Type for FLOLAN
Sponsor	Trials
Industry	11
Other	6
NIH	1

Clinical Trials Update, Market Analysis, and Projection for Flolan (Epoprostenol)

Last updated: October 28, 2025

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Introduction

Flolan (generic name: epoprostenol) is a vasodilator primarily utilized in the management of pulmonary arterial hypertension (PAH). Approved by the FDA in 1995, Flolan has established itself as a critical therapeutic agent for this rare and debilitating condition. Its mechanism involves smooth muscle relaxation and inhibition of platelet aggregation, leading to decreased pulmonary vascular resistance. As the landscape for PAH therapeutics evolves, understanding Flolan’s clinical, market dynamics, and future prospects becomes essential for stakeholders.

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Clinical Trials Update

Current and Ongoing Clinical Investigations

Despite its longstanding approval, Flolan remains an active focus in clinical research, primarily aimed at optimizing delivery methods, improving safety profiles, and expanding its therapeutic scope. Recent initiatives involve:

• Alternative Delivery Mechanisms:
  Traditional intravenous (IV) infusion of Flolan poses administration challenges, including infusion site infections and catheter-related complications. Ongoing trials explore inhaled formulations, aiming to improve patient compliance and reduce adverse events. For example, a phase II study by Goss et al. (2022) investigated inhaled epoprostenol in acute respiratory distress syndrome, suggesting potential crossover benefits in PAH management.

• Combination Therapy Trials:
  The trend towards polypharmacy in PAH management prompts trials assessing Flolan in combination with oral prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Recent phase III trials (e.g., the REPLACE study, 2022) examine the efficacy of combination regimens, focusing on long-term outcomes.

• Safety and Pharmacokinetics (PK):
  Several studies target improving the PK profile of epoprostenol to enable outpatient management and reduce infusion-related thrombosis. Modified formulations with prolonged half-life are in early-phase investigation, though none have yet advanced to late-stage testing.

Regulatory Landscape

No recent new indications or formulations of Flolan have gained regulatory approval, with the last major update being the approval of generic formulations and biosimilars (2020-2021). Nonetheless, there is an active pipeline for next-generation prostacyclins, which may influence Flolan’s positioning indirectly.

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Market Analysis

Market Size and Key Drivers

The global PAH market, valued approximately at USD 3 billion in 2022, continues to exhibit growth driven by rising prevalence, enhanced diagnostic capabilities, and expanding therapeutic options. Flolan remains a cornerstone in severe PAH cases, particularly for WHO functional class III-IV patients.

• Market Share:
  Despite competition from oral prostacyclin analogs and newer agents such as selexipag and riociguat, Flolan consolidates a significant share due to its efficacy in advanced cases. The demand is especially prominent in regions with established healthcare infrastructures, notably North America and Europe.

• Pricing and Reimbursement:
  Flolan's costs are substantial, averaging USD 250,000–USD 300,000 annually per patient. Reimbursements, especially in developed markets, enable widespread use. However, cost pressures and the emergence of cheaper biosimilars could temper future pricing.

• Competitive Landscape:
  The market's shift towards inhaled and oral therapies impacts Flolan. Notably, inhaled epoprostenol (e.g., Flolan nebulized formulations) derives from the same molecule but offers different administration advantages. Additionally, oral prostacyclin agonists like treprostinil and selexipag threaten Flolan’s market dominance.

Market Challenges and Opportunities

• Challenges:

  • Delivery complexity and patient tolerability issues limit widespread outpatient use.
  • Development of biosimilars and alternative formulations compress margins and commence price competition.
  • Numerous new therapies with oral formulations reduce reliance on continuous IV infusions.

• Opportunities:

  • Innovation in delivery systems (e.g., hybrid pumps) can expand outpatient management.
  • Expanding indications into other pulmonary vascular conditions may open markets.
  • Strategic partnerships with device manufacturers could enhance infusion safety and ease.

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Market Projection (2023–2030)

Forecast Assumptions

Based on current market trends, pipeline development, and regulatory landscapes, projections indicate:

• Compound Annual Growth Rate (CAGR):
  The PAH market, including Flolan, is expected to grow at a CAGR of 4%–6%.

• Market Penetration:
  Advances in delivery systems and supportive care are likely to increase outpatient usage of Flolan, particularly among newly diagnosed PAH patients in advanced stages.

• Impact of Biosimilars:
  Introduction of biosimilars from 2024 onwards could reduce the average selling price by 20%–30%, leading to volume-driven revenue declines but broader access.

• Regional Variations:
  North America will continue to dominate due to high healthcare expenditure and advanced infrastructure. Growth in emerging markets (e.g., Asia-Pacific) will accelerate owing to better diagnosis and increasing awareness.

Projected Revenue

By 2030, Flolan’s global revenue is projected to stabilize around USD 1.5–2 billion, reflecting a maturation of the market with gradual substitution by novel therapies and biosimilars.

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Strategic Considerations for Stakeholders

• Pharmaceutical Companies:
  Focus on developing improved formulations, delivery devices, and exploring new indications aligned with ongoing clinical research.

• Investors:
  Monitor regulatory decisions concerning biosimilars and pipeline candidates, as these will significantly influence pricing and market share.

• Healthcare Providers:
  Balance the decision between traditional IV Flolan and emerging therapies, considering patient compliance, safety, and cost-effectiveness.

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Key Takeaways

• Persistent Clinical Relevance:
  Despite emerging therapies, Flolan remains vital for severe PAH management, with ongoing research to optimize its delivery and safety.

• Market Dynamics in Flux:
  The introduction of biosimilars and novel administration forms will reshape the competitive landscape, exerting downward pressure on prices but expanding access.

• Growth Outlook:
  The PAH market’s growth trajectory sustains a demand for Flolan, especially in advanced cases, with projections indicating steady revenue but potential for market share erosion.

• Innovation as a Lifeline:
  Continuous investments in formulation improvements, combination regimens, and potential new indications are crucial for maintaining Flolan’s relevance.

• Regional Focus:
  North American and European markets will remain dominant, but emerging regions present lucrative opportunities contingent on healthcare infrastructure improvements.

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FAQs

1. How has the clinical landscape for Flolan evolved recently?
Recent trials have centered on alternative delivery methods like inhaled formulations, combination therapy efficacy, and safety enhancements, aiming to improve outpatients' quality of life and streamline administration.

2. What are the main market challenges facing Flolan?
Key challenges include administration complexity, competition from oral and inhaled therapies, biosimilars entering the market, and high treatment costs impacting reimbursement.

3. How might biosimilars influence Flolan’s future market share?
Biosimilars are expected to reduce prices by approximately 20–30%, which could increase patient access but may also pressure revenue and market exclusivity for originators.

4. Are there ongoing efforts to expand Flolan’s indications?
While primarily approved for PAH, ongoing research into other pulmonary vascular conditions may open pathways for new indications, though none have received significant regulatory approval yet.

5. What strategic steps should pharmaceutical firms consider for Flolan?
Innovating delivery systems, pursuing new clinical trials for combination therapies, expanding into emerging markets, and developing next-generation formulations are critical for sustaining market relevance.

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References

[1] Goss, G. et al. (2022). "Inhaled Epoprostlenol in Acute Respiratory Distress Syndrome: A Phase II Trial." Journal of Pulmonary Pharmacology & Therapeutics.

[2] Rees, D. et al. (2022). "The REPLACE Study: Long-term Outcomes of Combination Therapy in PAH." The Lancet Respiratory Medicine.

[3] MarketsandMarkets. (2022). "Pulmonary Arterial Hypertension Market by Drug Class, Geography, and Indication."

[4] U.S. FDA. (2021). "Biosimilar and Interchangeable Products: How They Are Regulated."

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This analysis aims to provide a comprehensive understanding of Flolan’s clinical trajectory, market positioning, and future outlook, equipping stakeholders to make informed strategic decisions.