Phosphodiesterase-4 (PDE4) Inhibitor Market Summary

• The PDE4 Inhibitor market in the 7MM is projected to grow at a significant CAGR by 2034 in leading countries (US, EU4, UK and Japan).

PDE4 Inhibitor Market and Epidemiology Analysis

• Phosphodiesterase 4 (PDE4) is an enzyme that specifically degrades cyclic adenosine monophosphate (cAMP), a second messenger involved in regulating various cellular processes. Predominantly expressed in immune and inflammatory cells, PDE4 plays a crucial role in modulating inflammatory responses.
• PDE4 can provide therapeutic benefits across a spectrum of diseases. PDE4 inhibitors are a class of drugs that work by blocking the phosphodiesterase-4 enzyme, thereby increasing intracellular cyclic AMP (cAMP) levels and reducing the production of pro-inflammatory cytokines. The development of selective PDE4 inhibitors aims to maximize efficacy while minimizing side effects, enhancing their potential as treatments for chronic inflammatory conditions.
• OTEZLA (apremilast), one of the initially approved PDE4 inhibitors and a notable blockbuster therapy, has maintained resilient performance despite the entry of generics. In Q4 2024, sales declined by 1% year-over-year to USD 624 million, primarily due to a 7% reduction in net selling price, partially offset by a 5% increase in volume. For the full year, the revenue was USD 2,126 million in 2024, a decrease of 3%, attributed to an 8% decline in pricing, mitigated by a 3% rise in volume, demonstrating continued demand and market stability amid pricing pressures.
• In April, 2024, OTEZLA (apremilast) got additional approval from the FDA for the treatment of pediatric patients aged 6 years and older with moderate to severe plaque psoriasis, expanding its indication to include a younger population affected by this chronic inflammatory skin condition.
• ZORYVE (roflumilast), a recently approved PDE4 inhibitor, generated USD 166.5 million in net product revenue in 2024, a 471% increase year-over-year, signaling strong market uptake and positioning for continued growth in 2025. Demand remains strong across all approved indications.
• Since launch, ZORYVE 0.3% cream for plaque psoriasis has surpassed 360,000 prescriptions by 2024. Its 0.15% formulation for atopic dermatitis and 0.3% foam for seborrheic dermatitis have filled over 33,000 and 246,000 prescriptions, respectively, underscoring its expanding clinical reach and the high unmet need in these conditions.
• Several PDE4 inhibitors are currently being evaluated in clinical trials. One of these assets in the late stage is Shionogi’s Zatolmilast, which is in stage III and being developed for Fragile X syndrome (FXS) and is anticipated to receive approval during the forecast period.
• In March 2025, Palisade Bio announced that two abstracts were selected for presentation at the Digestive Disease Week (DDW) 2025, including one designated as a Poster of Distinction. The presentations featured PALI-2108, a colon-specific PDE4 inhibitor prodrug, highlighting its potential in gastrointestinal therapeutic applications.
• In February 2025, Arcutis Biotherapeutics, Inc., a biopharmaceutical company specializing in immuno-dermatology, announced that the FDA had accepted a supplemental New Drug Application (sNDA) for ZORYVE (roflumilast) cream 0.05%. The once-daily topical PDE4 inhibitor was proposed for the treatment of mild to moderate atopic dermatitis in children aged 2 to 5 years.
• Chiesi Farmaceutici, UNION Therapeutics, Amgen, and several other companies are currently engaged in the development and production of PDE4 inhibitor, which has the potential to significantly impact and enhance the PDE4 Inhibitors market.

DelveInsight’s “ PDE4 Inhibitors Market Size, Target Population, Competitive Landscape, and Market Forecast – 2034” report delivers an in-depth understanding of the PDE4 Inhibitors, historical and Competitive Landscape, as well as the PDE4 Inhibitors market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The PDE4 Inhibitors market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted PDE4 Inhibitors market size across 7MM from 2020 to 2034. The report also covers current PDE4 inhibitors treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market’s potential.

Geography Covered

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2020–2034

PDE4 Inhibitors Understanding and Treatment Algorithm

PDE4 Inhibitors Overview

Phosphodiesterase-4 (PDE4) is an enzyme that regulates intracellular cAMP, a critical messenger in controlling inflammation and immune responses. Highly expressed in immune and epithelial cells, PDE4 plays a pivotal role in inflammatory conditions like psoriasis, COPD, and atopic dermatitis, making it a valuable target for therapeutic intervention.

PDE4 inhibitors work by increasing cAMP levels, suppressing pro-inflammatory cytokines. Approved drugs include OTEZLA (apremilast) for psoriasis and psoriatic arthritis, EUCRISA (crisaborole) for atopic dermatitis, and DALIRESP (roflumilast) for COPD. Newer formulations like ZORYVE (roflumilast cream) are expanding options in dermatology with improved tolerability and targeted delivery. Several approved candidates are currently under clinical trials to broaden the application of PDE4 inhibitors in managing other inflammatory and immune-related conditions.

Further details related to country-based variations are provided in the report

PDE4 inhibitor Treatment

PDE4 inhibitors are primarily used in dermatology and respiratory medicine for managing chronic inflammatory conditions like psoriasis, atopic dermatitis, and COPD. These agents offer an alternative to corticosteroids and immunosuppressants, particularly when long-term treatment is required, due to their targeted mechanism and favorable safety profile in mild-to-moderate disease.

In the treatment landscape, PDE4 inhibitors are often positioned as first as well as second-line or adjunct therapies when conventional options are ineffective or poorly tolerated. Their oral and topical formulations enhance flexibility in clinical use. For patients preferring non-steroidal options or requiring long-term disease control, PDE4 inhibitors offer a balanced efficacy-to-safety ratio.

The treatment landscape is evolving with PDE4 inhibitors under investigation for broader uses such as inflammatory bowel disease, lupus, and neuroinflammation. Improved delivery systems and subtype-specific inhibition aim to enhance efficacy and minimize adverse effects, supporting their integration into early treatment strategies and expanding their role across immune-mediated conditions.

Further details related to country-based variations are provided in the report

PDE4 Inhibitors Drug Chapters

The drug chapter segment of the PDE4 Inhibitors reports encloses a detailed analysis of PDE4 Inhibitors marketed drugs and late-stage pipeline drugs (Phase III and Phase II). It also helps understand the PDE4 Inhibitors' clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, the latest news, and press releases.

PDE4 Inhibitors Marketed Drugs

ZORYVE (roflumilast): Arcutis Biotherapeutics

ZORYVE is a next-generation topical PDE4 inhibitor developed by Arcutis Biotherapeutics. Targeting PDE4, a key enzyme in inflammation, roflumilast reduces pro-inflammatory mediators while enhancing anti-inflammatory responses. Available in both cream and foam formulations, ZORYVE offers a non-steroidal treatment option with favorable tolerability for chronic dermatologic conditions like plaque psoriasis, atopic dermatitis (AD), and seborrheic dermatitis.

ZORYVE first got FDA approvals as cream 0.3% for plaque psoriasis in July 2022 and after that it got multiple approvals for pediatric psoriasis ages 6–11yr (October 2023), cream 0.15% for mild to moderate atopic dermatitis in patients 6 and older (July 2024); and foam 0.3% for seborrheic dermatitis in individuals aged 9 and older (December 2023). These approvals broaden ZORYVE’s reach across age groups and dermatologic indications.

EUCRISA (crisaborole): Pfizer  

Eucrisa (crisaborole) is a topical phosphodiesterase 4 (PDE-4) inhibitor approved for the treatment of mild to moderate atopic dermatitis in adults and children as young as 3 months old. It is the first and only non-steroidal topical monotherapy designed to inhibit the PDE-4 enzyme in the skin. Overactivity of this enzyme is believed to play a role in the signs and symptoms of atopic dermatitis. While the exact mechanism of crisaborole in treating the condition is not fully understood, its ability to target PDE-4 is a key factor in its therapeutic effect.

It first got FDA approval in December 2016 for the treatment of Eczema. It also received additional approval from the FDA for use in children 3 months and older with mild to moderate atopic dermatitis.

Note: Detailed current therapies assessment will be provided in the full report of PDE4 Inhibitors

PDE4 Inhibitor Emerging Drugs

Zatolmilast: Shionogi 

Zatolmilast is the first selective PDE4D inhibitor being investigated for Fragile X syndrome (FXS), a genetic disorder causing intellectual disability and developmental delays. There are no FDA-approved treatments for FXS, and zatolmilast’s development represents a potential breakthrough. It has received Fast Track, Orphan Drug, and Rare Pediatric Disease designations.

Tetra Therapeutics is conducting clinical trials for Fragile X syndrome to assess zatolmilast’s safety and efficacy. The trials, including Phase 3 studies, focus on improving cognition and daily functioning in FXS patients. Positive early-phase results suggest that zatolmilast may provide significant benefits, offering hope for a much-needed cognitive treatment option for individuals with this rare genetic disorder.

PALI-2108: Palisade Bio

PALI-2108 is an orally administered, colon-targeted PDE4 inhibitor prodrug being developed by Palisade Bio for ulcerative colitis (UC). It supports a precision medicine approach aimed at identifying patient responders for future studies. The drug is designed for local action in the colon, minimizing systemic exposure and potential side effects.

A Phase 1 study is currently evaluating PALI-2108’s safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Preliminary results from the first three cohorts (15mg, 50mg, and 150mg) in healthy volunteers show that the drug was well tolerated with no dose-limiting toxicities or treatment-related dose reductions, supporting continued clinical development in ulcerative colitis patients.

Note: Detailed emerging therapies assessment will be provided in the final report.

Note: The emerging drug list is indicative, the full list will be given in the final report.

PDE4 Inhibitor Market Outlook 

The PDE4 inhibitors market is expected to witness steady growth through 2034, driven by rising cases of chronic inflammatory and autoimmune diseases such as psoriasis, atopic dermatitis, and COPD. PDE4 inhibitors offer targeted, non-steroidal anti-inflammatory effects with oral or topical administration, making them attractive alternatives to traditional therapies. Factors such as expanding indications, patient preference for non-invasive treatments, and improved safety profiles are accelerating market adoption across key regions, including the U.S., Europe, and Japan.

Currently approved PDE4 inhibitors include OTEZLA (apremilast), EUCRISA (crisaborole), ZORYVE (roflumilast), and others, which address conditions like psoriasis, atopic dermatitis, and eczema. OTEZLA leads the market with over USD 2.1 billion in 2024 revenue and expanded pediatric approval. ZORYVE has shown rapid uptake across multiple formulations, reaching over 600,000 prescriptions since launch. EUCRISA remains widely used in both pediatric and adult populations. These therapies reflect the class’s strong market presence and evolving treatment versatility.

Beyond the approved indications, several new disease areas are being explored for PDE4 inhibitors. Zatolmilast, a selective PDE4D inhibitor, is in Phase III trials for Fragile X syndrome, aiming to improve cognitive function in this rare neurodevelopmental condition. PALI-2108, a colon-targeted PDE4 prodrug, is in early development for ulcerative colitis, offering localized efficacy with reduced systemic exposure. Additional pediatric and dermatologic indications for ZORYVE are under FDA review, highlighting the class’s expanding therapeutic potential.

Multiple pharma giants, including Arcutis Biotherapeutics, Pfizer, and Amgen, are investing heavily in the space, while emerging players like Shionogi, Palisade Bio, UNION Therapeutics, and Chiesi Farmaceutici push innovation forward. As selectivity and safety profiles improve, PDE4 inhibitors are poised to become a cornerstone of immunotherapy across a growing spectrum of diseases.

With a growing number of clinical trials, expanding indications, and continued pharma investment, the PDE4 inhibitor landscape is positioned for accelerated expansion. As current studies mature, they will further define the scope of PDE4 inhibitors in inflammatory and immune-mediated diseases, solidifying their role as a transformative class of therapeutics.

PDE4 Inhibitor Drugs Uptake

This section focuses on the uptake rate of potential approved and emerging PDE4 Inhibitors expected to be launched in the market during 2020–2034.

PDE4 Inhibitors 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. 

The presence of numerous drugs at different stages is expected to generate immense opportunities for the PDE4 Inhibitors market growth over the forecasted period.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for PDE4 Inhibitor emerging therapies. 

The growing emphasis by key market players on securing robust patent protection is expected to accelerate the development of innovative pipeline products and drive sustained market growth. Strong intellectual property rights not only ensure exclusivity but also attract investment and partnerships. For instance, Palisade Bio’s European patent for PALI-2108 grants broad composition of matter claims, covering its gut microbiota-activated PDE4 inhibitor prodrug and extending exclusivity beyond 2042, significantly enhancing its commercial and clinical potential in ulcerative colitis.

Latest KOL Views on PDE4 Inhibitor

To keep up with current and future market trends, we take Industry Experts’ opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on PDE4 Inhibitors' evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along challenges related to accessibility.

DelveInsight’s analysts connected with 25+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as Charite University, Dana-Farber Cancer Institute and others.

Their opinion helps understand and validate current and emerging therapy treatment patterns or PDE4 inhibitors market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT 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.

Market Access and Reimbursement

Reimbursement may be referred to as the negotiation of a price between a manufacturer and payer that allows the manufacturer access to the market. It is provided to reduce the high costs and make the essential drugs affordable. Health technology assessment (HTA) plays an important role in reimbursement decision-making and recommending the use of a drug. These recommendations vary widely throughout the seven major markets, even for the same drug. 

In the US healthcare system, both Public and Private health insurance coverage are included. Also, Medicare and Medicaid are the largest government-funded programs in the US. The major healthcare programs, including Medicare, Continuing Medical Education (CME) program, the Children's Health Insurance Program (CHIP), and the state and federal health insurance marketplaces are overseen by the Centers for Medicare & Medicaid Services (CMS). Other than these, Pharmacy Benefit Managers (PBMs), and third-party organizations that provide services, and educational programs to aid patients are also present.

The availability of several savings programs in the U.S. has improved access to treatments like ZORYVE (roflumilast). The ZORYVE Direct Savings Card program allows eligible patients with commercial insurance to pay as little as USD 0 for their prescription. This initiative is designed to enhance affordability and ensure patients can begin treatment without financial delays, supporting broader use of ZORYVE for chronic inflammatory skin conditions.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Key Updates on PDE4 Inhibitors

• In April 2025, a preclinical study by Scripps Research scientists found that apremilast, an FDA-approved PDE4 inhibitor for inflammatory conditions, reduced both alcohol intake and pain sensitivity in models of alcohol use disorder (AUD). Published in JCI Insight, the findings supported its potential as a dual-acting therapy for AUD.
• In April 2025, Palisade Bio completed dosing in the Phase 1a portion of its ongoing Phase 1a/b study of PALI-2108 for the treatment of moderate-to-severe ulcerative colitis (UC). 
• In April, 2024, OTEZLA (apremilast) got additional approval from the FDA for the treatment of pediatric patients aged 6 years and older with moderate to severe plaque psoriasis, expanding its indication to include a younger population affected by this chronic inflammatory skin condition.
• In July 2024, the U.S. FDA approved Arcutis Biotherapeutics' ZORYVE® (roflumilast) for the treatment of atopic dermatitis (AD), the most common form of eczema affecting millions of people in the U.S. This approval marked a significant advancement in treatment options for individuals living with this chronic inflammatory skin condition.
• In June 2024, Verona Pharma announced that the U.S. Food and Drug Administration (FDA) approved OHTUVAYRE (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. This approval marked an important milestone in providing a new therapeutic option for COPD management.
• In June 2024, Alto Neuroscience announced the initiation of a Phase 2 double-blind, placebo-controlled study of the transdermal formulation of ALTO-101, a novel PDE4 inhibitor. The study is investigating ALTO-101 for the treatment of cognitive impairment associated with schizophrenia (CIAS). Data from this Phase 2 study is expected in the second half of 2025.

The abstract list is not exhaustive, will be provided in the final report

Scope of the PDE4 Inhibitors Market Report

• The report covers a segment of key events, an executive summary, and a descriptive overview of PDE4 Inhibitors, explaining its mechanism, and current and emerging therapies.
• Comprehensive insight into the PDE4 Inhibitor competitive landscape, and forecasts, the future growth potential of treatment rate, drug uptake, and drug information have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborate profiles of late-stage and prominent PDE4 Inhibitor therapies will impact the current landscape.
• A detailed review of the PDE4 Inhibitors market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis, expert insights/KOL views, and treatment preferences that help shape and drive the 7MM PDE4 Inhibitors market.

PDE4 Inhibitors Report Insights

• PDE4 Inhibitor Targeted Patient Pool
• PDE4 Inhibitor Therapeutic Approaches
• PDE4 Inhibitor Pipeline Analysis
• PDE4 Inhibitor Market Size and Trends
• Existing and Future Market Opportunity

PDE4 Inhibitors Report Key Strengths

• Ten-Year Forecast
• The 7MM Coverage 
• Key Cross Competition 
• PDE4 Inhibitor Drugs Uptake and Key Market Forecast Assumptions

PDE4 Inhibitors Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT)

Key Questions Answered in the PDE4 Inhibitors Market Report

• What was the total PDE4 Inhibitors market size, the market size by therapies, market share (%) distribution, and what would it look like in 2034? What are the contributing factors for this growth?
• Which PDE4 Inhibitor drug is going to be the largest contributor in 2034?
• Which is the most lucrative PDE4 Inhibitor market?
• Which PDE4 Inhibitor drug type segment accounts for the maximum PDE4 inhibitor sales?
• What are the pricing variations among different geographies for approved therapies?
• How the reimbursement landscape for PDE4 has Inhibitors evolved since the first one was approved? Do patients have any access issues that are driven by reimbursement decisions?
• What are the risks, burdens, and unmet needs of treatment with PDE4 Inhibitors? What will be the growth opportunities across the 7MM for the patient population on PDE4 Inhibitors?
• What are the key factors hampering the growth of the PDE4 Inhibitors market?
• What are the indications for which recent novel therapies and technologies have been developed to overcome the limitations of existing treatments?
• What key designations have been granted to the therapies for PDE4 Inhibitors?
• What is the cost burden of approved PDE4 Inhibitor therapies on the patient?
• Patient acceptability in terms of preferred therapy options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies? 

Reasons to buy PDE4 Inhibitors Market Report

• The report will help develop business strategies by understanding the latest trends and changing dynamics driving the PDE4 Inhibitors Market.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of indication-wise current and emerging therapies under the conjoint analysis section to provide visibility around leading indications.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders’ perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.