Sigma-1 Agonist Drug Class List

Drugs in Drug Class: Sigma-1 Agonist

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes	8,569,328		Y
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes	9,370,513
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes	10,881,657
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes	11,439,636

Sigma-1 Agonist Market Analysis and Financial Projection

The Sigma-1 receptor agonist drug class is emerging as a dynamic field with diverse therapeutic applications, active patent innovation, and a competitive pipeline. Below is a structured analysis:

Market Dynamics

• Pipeline Development:

  • Over 6 companies (e.g., Prilenia Therapeutics, Anavex Life Sciences, Algernon Pharmaceuticals) are advancing 6+ pipeline drugs, including Phase III candidates like pridopidine for Huntington’s disease[1].
  • Blarcamesine (ANAVEX2-73), a Sigma-1 activator by Anavex, is projected to drive market growth from $822.9M in 2026 to $1.08B by 2032 (CAGR: 4%)[15].
  • Repurposing of existing CNS drugs like fluvoxamine for COVID-19 highlights Sigma-1’s therapeutic versatility[6].

• Therapeutic Applications:

  • Neurodegenerative disorders: Huntington’s, Parkinson’s (via agonists like PRE-084)[3][12], and Alzheimer’s (blarcamesine)[15].
  • Psychiatric conditions: Depression, schizophrenia, and cocaine addiction[4][7][10].
  • Oncology: Ligands targeting breast, lung, and prostate cancers via caspase activation[2][8].
  • COVID-19: Sigma-1 agonists inhibit viral replication (e.g., fluvoxamine)[6].
  • Neuropathic pain: Antagonists like E-52862 show efficacy in Phase II trials[13].

• Key Growth Drivers:

  • Rising prevalence of neurodegenerative and psychiatric disorders[7][15].
  • Strategic collaborations (industry-academia partnerships)[16].
  • Expanding indications for existing drugs (e.g., cutamesine for ALS)[4].

• Challenges:

  • High attrition rates in clinical trials (e.g., Santen’s discontinued cutamesine)[4].
  • Competition from generics (e.g., pramipexole for Parkinson’s)[3].

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Patent Landscape

• Innovation Trends:
  • Selectivity improvements: Patents focus on high-affinity ligands (e.g., US8809381B2) to enhance specificity[17].
  • New indications: Recent patents cover fibrosis (WO2015118365A1)[5] and cancer via endothelial modulation (T1642/06)[8].
  • Mechanistic diversity: Agonists and antagonists target pathways like NMDA receptor regulation[12] and ER stress modulation[10].

Patent Highlights	Therapeutic Focus	Key Players
US8349898B2 (2013)	Cancer, addiction	Zogenix, Axsome Therapeutics[2]
T1642/06 (2007)	Cancer via endothelial targeting	Esteve Pharmaceuticals[8]
US8809381B2 (2014)	Neuropathic pain	University of Pavia[13]
CN114195808A (2022)	Depression, dyskinesia	Chinese researchers[14]

• Geographic Expansion: China’s 2022 patent for a depression-targeted agonist signals growing regional R&D[14].
• Litigation Risks: Expired patents (e.g., Santen’s cutamesine) may enable generic entry, but new formulations and combination therapies mitigate this[4][15].

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Competitive Landscape

• Leading Companies:

  • Prilenia Therapeutics: Phase III pridopidine for Huntington’s[1].
  • Anavex Life Sciences: Blarcamesine for Alzheimer’s/Parkinson’s[15].
  • Esteve Pharmaceuticals: Sigma-1 antagonists for neuropathic pain[13].

• Emerging Players:

  • NervGen Pharma: NVG-291 for spinal cord injury[9].
  • Chinese biotech firms: Novel agonists for CNS disorders[14].

• Strategic Moves:

  • Licensing agreements (e.g., M’s Science Corp licensing cutamesine)[4].
  • Focus on orphan drug designations to extend exclusivity[15].

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Future Outlook

• Opportunities:
  • Expansion into autoimmune diseases and fibrosis[5].
  • Biomarker-driven trials to validate receptor modulation[12].
  • Combination therapies (e.g., Sigma-1 agonists + NMDA modulators)[12].
• Risks:
  • Regulatory hurdles for CNS drugs due to safety concerns[7].
  • Market saturation from repurposed generics[6].

The Sigma-1 agonist landscape is poised for growth, driven by mechanistic diversity and strategic R&D, though clinical validation and IP management remain critical[1][4][16].

References

1. https://www.researchandmarkets.com/reports/5504276/sigma-1-receptor-agonists-pipeline-insight-2024
2. https://patents.google.com/patent/US8349898B2/en
3. https://www.oncotarget.com/article/8104/text/
4. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00564/full
5. https://patents.google.com/patent/WO2015118365A1/en
6. https://pmc.ncbi.nlm.nih.gov/articles/PMC7785036/
7. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.925879/full
8. https://www.epo.org/en/boards-of-appeal/decisions/t061642eu1
9. https://www.globenewswire.com/news-release/2025/03/05/3037544/28124/en/Chronic-Spinal-Cord-Injury-Pipeline-Market-Landscape-Report-2025-Featuring-Lineage-Cell-Therapeutics-NervGen-Pharma-Neuroplast-and-NurExone.html
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC2785038/
11. https://synapse.patsnap.com/drug/3f6c5d6320c9401fbf3a1ff03924c3b3
12. https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.685201/full
13. https://pubmed.ncbi.nlm.nih.gov/32539668/
14. https://www.bioworld.com/articles/687050-chinese-researchers-patent-sigma-1-receptor-agonists
15. https://www.coherentmarketinsights.com/industry-reports/global-blarcamesine-market
16. https://gervanora.com/report/Sigma-1-Receptors-Pipeline-Drugs-Opportunity-Assessments-Epidemiology-Forecast-Market-Dynamics-and-Pipeline-Analysis-H2-2020/GERPH906
17. https://patents.google.com/patent/US8809381B2/en