Drugs in MeSH Category 14-alpha Demethylase Inhibitors

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Aspiro	VORICONAZOLE	voriconazole	INJECTABLE;INTRAVENOUS	218533-001	Apr 3, 2024	AP	RX	No	No
Gedeon Richter Usa	FLUCONAZOLE	fluconazole	TABLET;ORAL	076432-001	Jul 29, 2004		DISCN	No	No
Ivax Sub Teva Pharms	FLUCONAZOLE	fluconazole	FOR SUSPENSION;ORAL	077523-001	Sep 12, 2007		DISCN	No	No
Sandoz Inc	VORICONAZOLE	voriconazole	TABLET;ORAL	200265-001	Dec 12, 2011	AB	RX	No	No
Sebela Ireland Ltd	ONMEL	itraconazole	TABLET;ORAL	022484-001	Apr 29, 2010		DISCN	Yes	No	8,486,456		Y
Ubi	VORICONAZOLE	voriconazole	INJECTABLE;INTRAVENOUS	211264-001	Mar 9, 2023	AP	RX	No	No
Woodward	FLUCONAZOLE IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER	fluconazole	INJECTABLE;INJECTION	077909-001	May 26, 2010	AP	RX	No	No

14-alpha Demethylase Inhibitors Market Analysis and Financial Projection

The market dynamics and patent landscape for 14-alpha demethylase inhibitors (CYP51 inhibitors) reflect a rapidly evolving therapeutic area driven by antifungal demand and expanding applications. These inhibitors target the enzyme critical for ergosterol biosynthesis in fungi, with azoles dominating current treatments. Below is a detailed analysis:

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Market Dynamics

Current Market Growth

The global antifungal drugs market is projected to grow from $17.26 billion in 2025 to $20.90 billion by 2030, with azoles accounting for a significant share due to their broad-spectrum activity and improved safety profiles[4][6]. Key drivers include:

• Rising incidence of invasive fungal infections (e.g., aspergillosis, candidiasis).
• Increased immunocompromised populations (e.g., HIV/AIDS, cancer patients).
• Development of next-generation azoles like oteseconazole (Mycovia Pharmaceuticals) and isavuconazole (Basilea Pharmaceutica)[1][14].

Pipeline Activity

• 12+ companies are actively developing 14-alpha demethylase inhibitors, with 12+ pipeline drugs across phases:
  • Preregistration: Oteseconazole for recurrent vulvovaginal candidiasis[14].
  • Phase III: Isavuconazole for invasive candidiasis[14].
  • Preclinical/Discovery: Multiple candidates targeting resistance mechanisms[6][11].

Competitive Landscape

• Key Players: Mycovia Pharmaceuticals, Basilea Pharmaceutica, Astellas Pharma, Merck & Co., and Pulmocide lead development[1][6].
• Emerging Trends: Focus on overcoming azole resistance via:
  • Structural modifications to improve target binding[9].
  • Dual-action molecules combining antifungal and anti-inflammatory properties[12].

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Patent Landscape

Therapeutic Expansion

• Antifungal Applications: Dominated by azole derivatives (e.g., fluconazole, voriconazole), with patents covering formulation improvements and combination therapies[12].
• Neurological Disorders: Yumanity Therapeutics holds patents for CYP51A1 inhibitors to treat TDP-43 proteinopathies in ALS and Alzheimer’s disease[2][10].

Key Patents and Innovations

• RS-21607: A selective inhibitor with picomolar affinity for mammalian CYP51, demonstrating potential for hypolipidemic applications[10].
• CBB3001: LSD1/KDM1 inhibitor with selectivity for teratocarcinoma cells, highlighting cross-target applications[8].
• Novel Formulations: Inhalable PUR 1900 (Pulmatrix) for pulmonary aspergillosis and ZP 059 (Zambon) for antifungal prophylaxis[1][6].

Collaborations and Licensing

• Strategic partnerships between academia and industry to address resistance (e.g., Pulmocide-CYP51A1 mutations[9]).
• Licensing of isavuconazole for orphan indications like mucormycosis[14].

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Challenges and Opportunities

Challenges	Opportunities
Azole resistance via CYP51 mutations[9]	Development of non-azole inhibitors (e.g., benzydamine/econazole combinations)[1]
Drug-drug interactions	Expanding into non-antifungal indications (e.g., neurology, oncology)[2][8]
Toxicity concerns in long-term use	Precision delivery systems (e.g., inhaled formulations)[6]

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Future Outlook

• Resistance Mitigation: Focus on CYP51A1 inhibitors with novel binding modes (e.g., water-mediated H-bond networks)[9].
• Diversification: Exploring CYP51’s role in cholesterol synthesis for cardiovascular and metabolic diseases[10].
• Global Health Impact: Addressing neglected tropical diseases (e.g., Chagas disease) with repurposed CYP51 inhibitors[6].

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Key Takeaway: The 14-alpha demethylase inhibitor landscape is marked by robust R&D activity, driven by antifungal needs and therapeutic diversification. While resistance remains a hurdle, innovations in drug design and delivery position this class for sustained growth across multiple disease areas.

References

1. https://www.businesswire.com/news/home/20220222006061/en/Global-14-Alpha-Demethylase-Inhibitors-Pipeline-Insight-Report-2022---ResearchAndMarkets.com
2. https://patents.justia.com/assignee/yumanity-therapeutics-inc
3. https://www.nlm.nih.gov/mesh/newmeshdescriptors_2024.html
4. https://www.mordorintelligence.com/industry-reports/anti-fungal-drugs-market
5. https://pmc.ncbi.nlm.nih.gov/articles/PMC4929062/
6. https://www.pharmaceutical-technology.com/data-insights/lanosterol-14-alpha-demethylase-drugs-in-development/
7. https://en.wikipedia.org/wiki/Sterol_14-demethylase
8. https://pubmed.ncbi.nlm.nih.gov/29439916/
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC7822023/
10. https://pubmed.ncbi.nlm.nih.gov/8161528/
11. https://www.globenewswire.com/news-release/2024/04/11/2861575/0/en/Sterol-14-Alpha-Demethylase-Inhibitor-Drug-Pipeline-Research-2024.html
12. https://www.wikidoc.org/index.php/Lanosterol_14_alpha-demethylase
13. https://meshb.nlm.nih.gov/record/ui?ui=D058888
14. https://www.globenewswire.com/news-release/2024/04/12/2862245/28124/en/14-alpha-Demethylase-Inhibitors-Drug-Landscape-Research-Report-2024-Comprehensive-Insights-on-12-Companies-and-12-Pipeline-Drugs.html
15. https://profiles.uchicago.edu/profiles/profile/28659