PDE4 Inhibitor Market: Competitive Landscape, Pipeline, and Market Analysis 2024

PDEs are a family of enzymes responsible for the hydrolysis and subsequent inactivation of cyclic nucleotides and are divided into 11 families based on sequence homogeneity, inhibitor sensitivity, and biochemical properties. Each enzyme within the PDE4 family specifically targets cAMP for degradation and consists of four subtypes (PDE4A to PDE4D). These enzymes are located within the brain and immunocompetent cells such as neutrophils, T lymphocytes, macrophages, and eosinophils. PDE4 Inhibitor works by accumulating the intracellular second messenger cAMP, downstream activation of protein kinase A (PKA), and subsequent phosphorylation of the transcription factor cAMP-response element binding protein (CREB).

Activation of this pathway modulates gene transcription of numerous cytokines, suppressing TNFα production and eventually inhibiting their proinflammatory and destructive properties. Inhibition of PDE4 suppresses airway inflammation extremely and relaxes smooth muscle via the elevation of the cAMP level. PDE4 Inhibitors have been verified as an effective therapeutic strategy for inflammatory conditions including asthma, chronic obstructive pulmonary disease (COPD), psoriasis, atopic dermatitis (AD), inflammatory bowel diseases (IBD), rheumatic arthritis (RA), lupus, and neuroinflammation. Increased prevalence of asthma and skin diseases are the key drivers for the PDE4 Inhibitor market. For instance, According to the World Health Organization 2023, Asthma affected an estimated 262 million people in 2019. Launch of newer products by the market players could seek opportunities that influence extensive research and development in PDE4 inhibitors. For instance, AstraZeneca’s Daliresp (Roflumilast) treats asthma and CNS disorders. Moreover, the development of novel molecules by many market players is coming up to overcome challenges in therapy. For instance, MediciNova’s Eyevinal (Ibudilast) for treating brain diseases and communicable diseases is under the various stages of clinical studies.

Key Market Developments:

• In October 2021, Arcutis Biotherapeutics has submitted a New Drug Application(NDA) for its topical PDE4 inhibitor Roflumilast cream in the treatment of mild to severe plaque psoriasis.
• In March 2020, Pfizer’s Eucrisa (Crisaborole) 2% Ointmnet has received FDA Supplemental New Drug Application (sNDA) for the Expanded indication in childrens as young as 3 month of age with mild to moderate atopic dermatitis.
• In April 2023, Zydus Lifesciences gets FDA approval to sell Roflumilast tablet 250 mcg for indication of COPD.

Approved Drug Molecules and Brand Names for PDE4 Inhibitor:

Drugs under the Pipeline for PDE4 Inhibitor:

Clinical Activity and Developments of PDE4 Inhibitor:

Till June 2023, more than 40 companies having approximately 43 molecules targetting the number of diseases. For these molecules, more than 107 clinical trials are being conducted and majority are in phase-2, phase-3 clinical trials by the players across the globe. For instance,

• In July 2020, Astrazeneca’s Daliresp (Roflumilast) found greater reductions in psoriasis signs and symptoms than placebo vehicle cream in phase 2b trial, funded by Arcutis Biotherapeutics.
• In February 2022, Pfizer has completed phase 3, double blind, randomised, vehicle controlled study for evaluating the safety and efficacy of Eucrisa (Crisaborole) in the pediatric and adult participants for atopic dermatitis.