HDAC Inhibitor Market: Competitive Landscape, Pipeline, and Market Analysis 2023

Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from an N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones and DNA expression is regulated by acetylation and de-acetylation. HDAC's action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases. HDAC involved biological functions including transcription, metabolism, oxidative stress, redox, protein degradation, and cell cycle among others. Histone deacetylases are expressed in different tumors; class I and II HDACs are general oncoproteins that interact with substrates and regulate gene expression to promote tumorigenesis and cancer development either individually or alongside co-repressors. The mechanism of action (MOA) of HDAC Inhibitor is  that work by HDIs block HDAC enzyme activity by binding to the zinc ion in the catalytic site, which blocks substrate access to the site and histone deacetylase inhibitors exert their anti-tumour effects via the induction of expression changes of oncogenes or tumor suppressors. HDAC Inhibitors are used for the treatment of lymphoma, blood coagulation disorders, leukemia, sarcoma, hematologic diseases, Hodgkin disease, gastrointestinal diseases, multiple myeloma, vascular diseases, and breast neoplasm among others. Increased prevalence of sarcoma and lymphoma are the key drivers for the HDAC Inhibitor market. For instance, According to the World Health Organization 2023, Non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States, accounting for about 4% of all cancers. Launch of newer products by the market players could seek opportunities that influence extensive research and development in  HDAC inhibitors. For instance, Chipscreen Bioscience’s Epidaza (Chidamide) is used to treat relapsed or refractory peripheral T cell lymphoma (PTCL). Moreover, the development of novel molecules by key players are coming up to overcome challenges in therapy. For instance, Italfarmaco’s Givinostat (ITF2357) for the treatment of juvenile idiopathy is under the various stages of clinical studies.

Key Market Developments:

• In December 2019, Chipscreen Bioscience’s Epidaza (Chidamide) received the approval from China’s National Medical Products Administration (NMPA) for the indication of breast cancer.
• In December 2022, 4SC’s Resminostat received European Medicine Agency approval for its application of pre-authorization eligibility request in cutaneous T cell lymphoma and resminostat was eligible for submission of an application for a Union Marketing Authorisation according to the centralized procedure as detailed in Regulation (EC) No 726/2004.

Approved Drug Molecules and Brand Names for HDAC Inhibitor:

• Epidaza (Chidamide)
• Kinselby (Resminostat)
• Istodax (Romidepsin)

Drugs under the Pipeline for HDAC Inhibitor:

• Zolinza (Vorinostat)
• Jingzhuda (Enostat)
• Beleodaq (Belinostat)
• Givinostat (ITF2357)nti
• Mocetinostat (MGCD0103)
• Abexinostat (CG-781)
• Pracinostat (SB939)
• FX 322
• Tinostamustine (EDO-S101)
• Domatinostat (4SC-202)
• Fimepinostat (CUDC-907)
• Ivaltinostat (CG-745)
• Quisinostat (JNJ 26481585)
• CUDC-101
• Sulforadex (Sulforafan Alfadex)
• Nanatinostat (Vrx-3996)
• Panobinostat (MTX110)
• Remetinostat (SHP-141)
• Zabinostat (CXD101)
• REC-2282
• Alteminostat (CKD-581)
• Tefinostat (CHR-2845)
• Valproic Acid (CT-010)
• GSK3117391
• HG146
• Lunaphen (4 Phenyl Butyrate Prolonged-Release)
• NBM-BMX
• RDN-929
• Bocodepsin (OKI-179)
• Avugane (Valproic Acid)
• Baceca (Valproic Acid)
• EVP-0334
• MPT0E028
• Savicol (Valproic Acid)
• Bisthianostat (CF367)
• Spiruchostatin A (OBP-801)
• Trichostatin A (VTR-297)
• Valproic Acid/Prednisone(VAL001)

Clinical Activity and Developments of HDAC Inhibitor:

As of June 2023, more than 55 companies have approximately 42 molecules targeting 625 diseases. For these molecules, more than 296 clinical trials are being conducted and the majority are in phase-2, phase-3 clinical trials. For instance,

• In June 2023, Edding Pharma completed the phase 2 study of epigenetic therapy with Azacitidine and Entinostat with concurrent nivolumab in subjects with metastatic non-small cell lung cancer.
• In February 2022, 4SC AG completed phase 1, Open-label Study of Resminostat for evaluating the Absorption, Metabolism, Excretion in a Single Oral Dose in Healthy Male subjects.