Retinoic acid receptors (RAR) and Retinoid X Receptors (RXR) Market: Competitive Landscape, Pipeline, and Market Analysis 2023

Retinoic acid receptors (RAR) and Retinoid X Receptors (RXR) are nuclear receptors that are targets for various kinds of diseases. RAR is activated by all-trans-retinoic acid and 9-cis retinoic acid. RAR are ligand-controlled transcription factors that function as heterodimers with RXRs and regulate cell growth, cell differentiation, cell survival, and cell death. RAR has three subtypes – α,β, and γ that form heterodimer complexes with RXR to orchestrate complex events such as organ homeostasis, reproduction, and immune function. Without a ligand, the RAR/RXR dimer binds to hormone response elements known as retinoic acid response elements (RAREs) that form complexes with corepressor proteins. Binding of an agonist ligand to the RAR results in corepressor dissociation and coactivator protein recruitment, facilitating the transcription of downstream target genes into mRNA and, ultimately, protein. The success of retinoic acid-based therapy in the treatment of acute promyelocytic leukemia (APL) and the improved understanding of the biological roles of RAR and RXR have led to the development of RAR and RXR modulators for cancer therapy. Bexarotene selectively binds to and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXR can form heterodimers with various receptor partners, including retinoic acid receptor (RAR), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptor (PPAR). RAR/RXR has been associated with regulating inflammation and the immune system, maintaining synaptic plasticity and axonal regeneration. These drugs have been used to treat many diseases, such as Acne Vulgaris, Cutaneous T cell Lymphoma, Atopic Dermatitis, Psoriasis, Papulosquamous skin disease, and many others. Extensive research is being conducted globally to discover new and novel molecules for RAR/RXR, like tretinoin used for treating Acne Vulgaris. The development and launch of new products will thus increase the market's revenue in the forecasted years. Many of these drugs are on the market, while many are in ongoing clinical trials. Many companies have various products in their pipelines, with 45 products in different stages of clinical trials. 8 products in Phase 4, 10 in Phase 3, 8 in Phase 2, and 1 in Phase 1 of the clinical trials.

Key Developments of RAR/RXR

• In October 2019, FDA approved Aklief (trifarotene) 0.005% cream for the topical treatment of Acne Vulgaris.
• In December 2019, FDA approves Arazlo (tazarotene) 0.045% lotion for the treatment of Acne Vulgaris.
• In August 2018, FDA approved Altreno (tretinoin) 0.005% lotion for the treatment of Acne Vulgaris.

Approved molecules of RAR/RXR

• Targretin oral (bexarotene oral)
• Toctino (alitretinoin)
• Duobrii (halobetasol/tazarotene)
• Aklief (trifarotene)
• isotretinoin
• Altreno (tretinoin)
• Tri-Luma (fluocinolone acetonide/hydroquinone/tretinoin)
• Arazlo (tazarotene lotion)

Drugs in the Pipeline of RAR/RXR

• Vesanoid (Tretinoin)
• Amnolake (Tamibarotene)
• Sohonos (Palovarotene)
• UAB30
• Bexarotene/Betamethasone Dipropionate (LAS 41004)
• IRX4204
• Targretin Gel (Bexarotene Topical)
• Benzoyl Peroxide/Clindamycin/Adapalene (IDP-126)
• Benzoyl Peroxide/Tretinoin (IDP-120)
• S6G5T-3
• Twyneo (3% Microencapsulated Benzoyl Peroxide/0.1% Microencapsulated Tretinoin)
• Isotretinoin Topical (TMB-001)
• Fenretinide Nanoparticle (ST-001 Nanofenretinide)
• Fenretinide Oral (LAU-7b)
• IRX5183
• PLX 200
• Panretin (Alitretinoin Topical)
• Adapalene/Minocycline (FCD105)
• Tazarotene (GRI-0621)

Clinical Activity and Developments of RAR/RXR

As of July 2023, 45 companies have many products for 358 diseases. For these diseases, many trials are being conducted by players globally. For instance,

• Kafrelsheikh University is conducting a Phase 4 clinical trial to investigate the the potential role of aerosolized retinoic acid, a potent vitamin a metabolite for treating covid-19 anosmia and retinoic acid insufficiency a novel approach for regaining sense of smell that was expected to complete by January 2022.
• Children’s Oncology Group is conducting a Phase 3 clinical trial to study the impact of Arsenic Trioxide and Trans Retinoic acid on patients with newly diagnosed Acute Promyelocytic Leukemia (APL) that is expected to complete by December 2025.
• LEO Pharma is conducting a Phase 3 clinical trial to compare the efficacy and safety of delgocitinib cream 20 mg/g twice-daily with alitretinoin capsules once-daily in adult participants with severe chronic hand eczema that is expected to complete by December 2023.