CLINICAL TRIALS PROFILE FOR ESBRIET

All Clinical Trials for ESBRIET

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001596 ↗	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome	Completed	National Human Genome Research Institute (NHGRI)	Phase 2	2005-09-01	Hermansky-Pudlak Syndrome (HPS) is an inherited disease that results in decreased pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The most serious complication of the disease is pulmonary fibrosis and typically causes death in patients 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical research studies on the disease have been conducted. Neither the full extent of the disease nor the basic cause of the disease is known. There is no known treatment for HPS. The drug pirfenidone blocks the biochemical process of inflammation and has been reported to slow or reverse pulmonary fibrosis in animal systems. In this study researchers will select up to 40 HPS patients diagnosed with pulmonary fibrosis. The patients will be randomly divided into 2 groups. The patients will not know if they are taking pirfenidone or a placebo "sugar pill". 1. Group one will be patients who will receive pirfenidone. 2. Group two will be patients who will receive a placebo "sugar pill" The major outcome measurement of the therapy will be a change in the lung function (forced vital capacity). The study will be stopped if one therapy proves to be more effective than the other.
NCT00001596 ↗	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome	Completed	William Gahl, M.D.	Phase 2	2005-09-01	Hermansky-Pudlak Syndrome (HPS) is an inherited disease that results in decreased pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The most serious complication of the disease is pulmonary fibrosis and typically causes death in patients 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical research studies on the disease have been conducted. Neither the full extent of the disease nor the basic cause of the disease is known. There is no known treatment for HPS. The drug pirfenidone blocks the biochemical process of inflammation and has been reported to slow or reverse pulmonary fibrosis in animal systems. In this study researchers will select up to 40 HPS patients diagnosed with pulmonary fibrosis. The patients will be randomly divided into 2 groups. The patients will not know if they are taking pirfenidone or a placebo "sugar pill". 1. Group one will be patients who will receive pirfenidone. 2. Group two will be patients who will receive a placebo "sugar pill" The major outcome measurement of the therapy will be a change in the lung function (forced vital capacity). The study will be stopped if one therapy proves to be more effective than the other.
NCT00076102 ↗	Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas	Completed	National Cancer Institute (NCI)	Phase 2	2004-07-21	Background: Neurofibromatosis Type 1 (NF1) is an autosomal dominant, progressive genetic disorder characterized by diverse clinical manifestations. Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas, which are benign nerve sheath tumors that may cause severe morbidity and possible mortality. The histopathology of these tumors suggests that events connected with formation of fibroblasts might constitute a point of molecular vulnerability. Gene profile analysis demonstrates overexpression of fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor in plexiform neurofibromas in patients with NF1. Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors. Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults with progressive plexiform neurofibromas. A phase I trial of pirfenidone in children and young adults with NF1 and plexiform neurofibromas was completed, and has established the phase II dose (the dose resulting in a mean drug exposure [AUC] not more than 1 standard deviation below the mean drug exposure [AUC] in adults who received pirfenidone at the dose level demonstrating activity in fibrosing conditions). Pirfenidone has been well tolerated. Objectives: To determine whether pirfenidone increases the time to disease progression based on volumetric measurements in children and young adults with NF1 and growing plexiform neurofibromas. To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas. To describe and define the toxicities of pirfenidone. Eligibility: Individuals (greater than or equal to 3 years to less than or equal to 21 years of age) with a clinical diagnosis of NF1 and inoperable, measurable, and progressive plexiform neurofibromas that have the potential to cause substantial morbidity. Design: The phase II dose will be used in a single stage, single arm phase II trial The natural history of the growth of plexiform neurofibromas is unknown. For this reason, time to disease progression on the placebo arm of an ongoing National Cancer Institute (NCI) Pediatric Oncology Branch (POB) placebo-controlled, double-blind, cross-over phase II trial of the farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive plexiform neurofibromas. Funding source - Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD)
NCT02262299 ↗	European Trial of Pirfenidone in BOS, A European Multi-center Study	Completed	Rigshospitalet, Denmark	Phase 2/Phase 3	2015-05-01	A European multi-centre, randomised, double-blind placebo-controlled trial of Pirfenidone in bronchiolitis-obliterans-syndrome grade 1-3 in lung transplant recipients. Randomized double blinded, placebo controlled study. Eligible patients are to be randomized in a 1:1 ratio to receive either Pirfenidone 2403 mg/d or the matching placebo treatment for 6 months. Primary objective To evaluate the effect of Pirfenidone on the change in FEV1 in liters over 6 months in lung transplant recipients with bronchiolitis obliterans syndrome.
NCT02598193 ↗	Safety and Tolerability Study of Pirfenidone in Combination With Nintedanib in Participants With Idiopathic Pulmonary Fibrosis (IPF)	Completed	Hoffmann-La Roche	Phase 4	2016-01-14	This clinical study will evaluate the safety and tolerability of combination treatment of nintedanib and pirfenidone in participants with IPF. Eligible participants must have received pirfenidone for at least 16 weeks on a stable dose. Nintedanib will be added on Day 1 of the study as a combination treatment for IPF for 24 weeks.
NCT02622477 ↗	Clinical Progression of Mild to Moderate Idiopathic Pulmonary Fibrosis (IPF) Under a Therapy With Esbriet® (Pirfenidone)	Completed	InterMune Deutschland GmbH		2014-06-01	The purpose of the study was to assess the clinical outcome of patients with a mild to moderate IPF after a one-year therapy with Esbriet® (Pirfenidone).

Clinical Trial Conditions for ESBRIET

Condition Name

Condition Name for ESBRIET
Intervention	Trials
Idiopathic Pulmonary Fibrosis	5
Disorder Related to Lung Transplantation	2
Interstitial Lung Disease	2
Chronic Kidney Disease	1

Condition MeSH

Condition MeSH for ESBRIET
Intervention	Trials
Pulmonary Fibrosis	8
Idiopathic Pulmonary Fibrosis	5
Fibrosis	5
Idiopathic Interstitial Pneumonias	4

Clinical Trial Locations for ESBRIET

Trials by Country

Trials by Country for ESBRIET
Location	Trials
United States	62
Italy	14
Spain	10
Canada	7
Germany	5

Trials by US State

Trials by US State for ESBRIET
Location	Trials
California	5
Maryland	4
Michigan	4
New York	4
Massachusetts	4

Clinical Trial Progress for ESBRIET

Clinical Trial Phase

Clinical Trial Phase for ESBRIET
Clinical Trial Phase	Trials
Phase 4	2
Phase 2/Phase 3	1
Phase 2	12

Clinical Trial Status

Clinical Trial Status for ESBRIET
Clinical Trial Phase	Trials
Completed	9
Recruiting	4
Active, not recruiting	3

Clinical Trial Sponsors for ESBRIET

Sponsor Name

Sponsor Name for ESBRIET
Sponsor	Trials
Genentech, Inc.	6
Hoffmann-La Roche	5
University of California, San Francisco	2

Sponsor Type

Sponsor Type for ESBRIET
Sponsor	Trials
Other	23
Industry	13
NIH	4

Last updated: July 26, 2026

Esbriet (Pirfenidone) Clinical Trials Update, Market Analysis, and Exclusivity/Competition Outlook (2026)

Esbriet (pirfenidone) is the key marketed antifibrotic for idiopathic pulmonary fibrosis (IPF) under the brand trademark “Esbriet” (Bayer). Current business relevance centers on (1) remaining IPF lifecycle protection, (2) trial activity versus newer combination regimens and competing antifibrotics, and (3) expected market share pressure from authorized generic entry where patent and regulatory barriers fall.

What is Esbriet (pirfenidone) and what clinical-trial programs are active in IPF?

Short answer: Pirfenidone clinical development in IPF is concentrated in confirmatory and regimen studies that test pirfenidone-based combinations, alternative endpoints, and real-world/biomarker-linked outcomes, with ongoing industry focus on standard-of-care positioning against nintedanib and emerging pipeline antifibrotics.

Core clinical focus areas for pirfenidone in IPF

1. Combination therapy against disease progression
   • Pirfenidone is evaluated with other agents aimed at reducing progression after standard antifibrotic initiation.
2. Earlier intervention and subgroup response
   • Trials target treatment effects in less advanced disease stages and in clinically relevant subgroups.
3. Endpoint and biomarker strategy
   • Studies explore surrogate endpoints (radiographic and functional) to support faster signal detection and post-approval evidence generation.

How trial activity affects market positioning

• Trials that show incremental benefit for pirfenidone regimens can extend prescribing inertia even in the face of generic erosion by keeping the brand aligned with guideline language and payer rationales.
• Negative or neutral combination results typically accelerate price pressure, because formularies and payers treat the antifibrotic “class” as interchangeable.

How does pirfenidone clinical efficacy compare with nintedanib in IPF?

Short answer: Both pirfenidone and nintedanib slow IPF decline but target different mechanisms; comparative positioning in practice has been driven by tolerability, dosing schedule, and payer-managed formulary access rather than a single head-to-head efficacy superiority result.

Practical drivers of relative use

• Tolerability profile: GI and photosensitivity risk management for pirfenidone vs. diarrhea and liver enzyme monitoring for nintedanib.
• Adherence: dosing and dose-modification pathways influence real-world persistence.
• Formulary dynamics: payers often sequence drugs by lowest net cost and anticipated budget impact.

Market implication

If payers treat antifibrotics as class substitutes, generic entry for either drug can reshape the other drug’s commercial curve through benchmark-driven pricing.

When does Esbriet lose exclusivity and what drives generic entry risk?

Short answer: The practical exclusivity question for Esbriet is not a single date. It is the intersection of patent expirations (drug substance, composition, methods, and formulation), regulatory exclusivities (where applicable), and Orange Book–listed blocking patents.

What to monitor for generic risk

• Orange Book patent list changes
  • Removal of patents or narrowing claims can shift timing.
• Paragraph IV litigation cadence
  • Settlements often set an agreed “launch date” that caps damages risk even before a true expiration.
• List price vs. net price erosion
  • Even without immediate launch, discounting can pre-load margin compression.

What patents protect Esbriet (pirfenidone) and how strong is the estate?

Short answer: Pirfenidone’s commercial protection historically relies on composition/formulation and method-of-use claims in addition to earlier foundational patents. The strength today depends on whether remaining claims are actively asserted or still listed as “blocking” in the FDA Orange Book.

Patent estate structure commonly relevant to pirfenidone brands

• Drug substance / crystalline forms
• Composition claims (drug product combinations, excipient choices)
• Formulation and manufacturing method patents
• Method-of-use claims tied to IPF dosing and patient-selection language

How that affects launch barriers

• If remaining claims are narrow (specific polymorph/formulation), generics can potentially design around and still challenge product similarity.
• If remaining claims are broad method-of-use or dosing regimen claims, Paragraph IV and design-around viability drops, raising litigation probability.

What is the Orange Book status of Esbriet (pirfenidone) and which patents block generics?

Short answer: Orange Book status determines whether ANDA filers must litigate blocking patents; blocking status typically maps to composition and method-of-use claims listed with “Orange Book” coverage.

Key Orange Book readouts to model launch timing

• “Active” patent listings as of the most recent FDA update cycle
• Patent expiration dates for each listed patent family
• Whether patents are listed for the relevant dosage form(s) and strength(s)
• Use codes and statement types that indicate the legal basis for exclusivity

What Paragraph IV challenges exist for Esbriet and what settlements have been reached?

Short answer: The generic-entry path for Esbriet usually involves Paragraph IV challenges against Orange Book-listed blocking patents, with potential for settlement agreements that delay launch.

How to translate litigation into commercial projection

• A settlement with a defined end date functions like a de facto launch barrier.
• If litigation ends without a settlement, the earliest generic launch is governed by:
  • patent expiration,
  • court rulings (non-infringement or invalidity),
  • and FDA approval timing for ANDAs.

What formulations of Esbriet (capsules, dosing schedule) are protected and how does that affect generic design-around?

Short answer: Esbriet’s marketed dosage forms are typically capsule-based. Generic viability depends on overcoming formulation equivalence standards and, where relevant, navigating formulation patent claims tied to excipient systems or manufacturing methods.

Generic design-around pathways

• Different excipient composition that avoids literal formulation claim elements
• Alternative solid-state forms if the brand’s solid-state patents remain enforceable
• Manufacturing route changes aimed at noninfringement under method claims

How does Esbriet market performance project under generic erosion and payer substitution?

Short answer: The biggest revenue risk for Esbriet is net price erosion and share loss following generic adoption. Market projection should assume a step-change in ASP (average selling price) post-first generic launch, followed by further compression as additional entrants increase competition.

Projection framework (business model)

1. Baseline volume anchored to IPF prevalence and treated-patient growth
2. Adoption curve for antifibrotic class switching
   • After generic entry, substitution accelerates if payers treat pirfenidone and competing antifibrotics as alternatives.
3. Net price and rebate behavior
   • Brand manufacturers often respond with rebate re-optimization and patient support programs.
4. Geographic depth
   • EU and other markets may differ by patent landscape and national reimbursement.

Expected shape of the revenue curve

• Pre-generic period: modest growth or plateau driven by guideline adherence and incident IPF case management.
• First generic entry: abrupt margin compression, with partial volume resilience via clinician familiarity.
• Multi-generic period: further discounting and switch to lowest net cost options.

Which companies are likely to compete with Esbriet as generics and new antifibrotics scale?

Short answer: Competition splits into two layers:

1. Generic manufacturers with ANDA approvals for pirfenidone
2. Newer pipeline antifibrotics or combination regimens that expand the standard-of-care beyond first-line monotherapy

Commercial implications for strategy

• If generics enter quickly, brand differentiation relies on:
  • patient support programs,
  • adherence tools,
  • and evidence-based dosing optimization tied to trial endpoints.
• If clinical evidence supports better regimen outcomes, brand can defend share even with price pressure.

What biosimilar or biologics risk exists for Esbriet?

Short answer: Biosimilar risk is not a typical driver for Esbriet because pirfenidone is a small-molecule drug, not a biologic.

What does the competitive landscape look like: pirfenidone vs other IPF antifibrotics?

Short answer: The competitive set is dominated by:

• nintedanib (Ofev) as the principal alternative antifibrotic
• pirfenidone generics once approvals are effective in the relevant jurisdiction
• emerging combination regimens that may reposition pirfenidone in line with new guidelines

Market projection driver

• If payers maintain “either-drug” placement with cost minimization, any generic entry for pirfenidone is likely to pull demand away from branded supply and also pressure nintedanib net pricing indirectly.

Key takeaways

• Esbriet (pirfenidone) remains anchored to IPF as a core antifibrotic, with trial activity focused on combination regimens, subgroup response, and endpoint strategy.
• The commercial outlook in 2026 is primarily determined by legal/regulatory launch timing (Orange Book blocking patents and Paragraph IV outcomes) and payer-driven substitution once generics gain effective launch.
• Market projections should assume a sharp net price decline after first generic entry, followed by continued ASP erosion as additional suppliers compete, with share erosion accelerating under cost-led formularies.

FAQs

1. What trial endpoints matter most for pirfenidone positioning in IPF (FVC, progression-free survival, biomarkers)?
2. How do tolerability and dose-modification rules affect real-world persistence for Esbriet versus nintedanib?
3. What Orange Book patent types most commonly block ANDA filers for small-molecule antifibrotics like pirfenidone?
4. How do Paragraph IV settlements typically translate into launch dates and damages risk for brand manufacturers?
5. How should investors model IPF antifibrotic market share under cost-led payer switching after generic entry?

References (APA)

1. U.S. Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA.
2. ClinicalTrials.gov. Studies of pirfenidone for idiopathic pulmonary fibrosis. U.S. National Library of Medicine.