Timolol topical - Senju Pharmaceutical
Alternative Names: IstalolLatest Information Update: 21 Jan 2022
At a glance
- Originator Senju Pharmaceutical
- Class Amino alcohols; Antiglaucomas; Antihypertensives; Ischaemic heart disorder therapies; Morpholines; Propanolamines; Small molecules; Thiadiazoles
- Mechanism of Action Beta-adrenergic receptor antagonists
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity No
Highest Development Phases
- Marketed Glaucoma; Ocular hypertension
Most Recent Events
- 04 Feb 2019 Chemical structure information added
- 06 Jun 2012 ISTA Pharmaceuticals has been acquired by Bausch & Lomb
- 29 Jul 2004 Launched for Ocular hypertension in USA (Topical)
Development Overview
Introduction
Senju Pharmaceutical Co. Ltd., (USA), has developed a topical ophthalmic solution formulation of timolol, applied as drops, for the treatment of glaucoma and ocular hypertension. Senju's timolol formulation is applied once daily, compared with the twice-daily application required for other similar formulations. It is marketed in the US by a licensee company, ISTA Pharmaceuticals (Bausch & Lomb), for the treatment of glaucoma.
In October 2004, the US FDA granted ISTA's timolol a "BT" rating. This means that prescriptions of the drug cannot be legally substituted at pharmacies with generic timolol maleate solutions [1] .
Company Agreements
ISTA Pharmaceuticals (Bausch & Lomb) holds US marketing rights to the timolol formulation, which it calls Istalol®. ISTA acquired the US marketing rights to Istalol® from AcSentient in May 2002, when it acquired substantially all of the assets of AcSentient. AcSentient had previously acquired the rights to the product from Senju [2] . The full rights and obligations of AcSentient under the Senju licence agreements were assigned to ISTA as a part of the agreement between ISTA and AcSentient. ISTA has paid Senju non-refundable milestone payments of $US4 million in relation to the development and regulatory approval of both Istalol® and Xibrom® (bromfenac ophthalmic solution), and is required to make royalty payments based on product sales. The licence agreement with Senju for Istalol® will co-terminate with the last-to-expire licensed patent.
In December 2006, Senju granted DreamPharma (a subsidiary of Alvogen) exclusive development, manufacturing and marketing rights for timolol for the treatment of glaucoma in South Korea. In August 2014, DreamPharma was acquired by Alvogen [3] . Subsequently, in June 2015, DreamPharma Corporation merged with KunWha Pharmaceutical to form Alvogen Korea [4] .
ISTA Pharmaceuticals was acquired by Bausch & Lomb in June 2012 [5] .
Prior to the acquisition, ISTA had a supply agreement with Bausch & Lomb to manufacture commercial quantities of Istalol®. In December 2003, ISTA submitted to the FDA information needed to qualify Bausch & Lomb as an alternative manufacturer for timolol.
Key Development Milestones
The marketing of Senju Pharmaceutical's topical formulation of timolol, Istalol®, in the US for the treatment of glaucoma and ocular hypertension was reported on Senju's website to be continuing in November 2012.
In June 2004, Senju Pharmaceutical's formulation of timolol was approved by the US FDA for the treatment of glaucoma and ocular hypertension [6] [7] . The product was launched ahead of schedule in the US, its first global market, in July 2004 [8] .
Senju has announced that its phase III trial results of timolol showed that its formulation has comparable efficacy and safety compared with timolol maleate [9] .
Patent Information
Senju Pharmaceutical has been granted patents for its topical timolol formulation.
Drug Properties & Chemical Synopsis
- Route of administration Topical
- Formulation Drops
- Class Amino alcohols, Antiglaucomas, Antihypertensives, Ischaemic heart disorder therapies, Morpholines, Propanolamines, Small molecules, Thiadiazoles
- Target Beta-adrenergic receptor
- Mechanism of Action Beta-adrenergic receptor antagonists
-
WHO ATC code
S01E-D01 (Timolol)
-
EPhMRA code
S1E2 (Miotics and antiglaucoma preparations, topical)
- Chemical name (S)-1-(tert-butylamino)-3-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)propan-2-ol
- Molecular formula C13 H24 N4 O3 S
- SMILES C(C(COC1=NSN=C1N1CCOCC1)O)NC(C)(C)C
-
Chemical Structure
- CAS Registry Number 26839-75-8
Biomarkers Sourced From Trials
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Timolol topical - Senju Pharmaceutical | 12S-HHT | Eligibility Criteria |
| 13-cis-Retinoic acid | Eligibility Criteria | |
| ACE2 | Detailed Description | |
| ACVRL1 | Eligibility Criteria | |
| aldo-keto reductase family 1, member C4 | Eligibility Criteria | |
| Allergic rhinitis | Eligibility Criteria | |
| ARL6IP4 | Arm Group Description, Arm Group Label | |
| bestrophin 1 | Detailed Description | |
| BMP9 | Outcome Measure | |
| cataract, congenital, total | Eligibility Criteria | |
| cerebellar degeneration related protein 1 | Eligibility Criteria | |
| CYP2D6 | Eligibility Criteria | |
| CYP2D7 | Eligibility Criteria | |
| cysteine rich secretory protein 2 | Outcome Measure | |
| Endoglin | Outcome Measure | |
| F-box and leucine rich repeat protein 15 | Eligibility Criteria | |
| Ferritin | Outcome Measure | |
| FSH | Eligibility Criteria | |
| glutathione synthetase | Outcome Measure | |
| Hand skill, relative | Brief Title | |
| HHT3 | Eligibility Criteria | |
| L-Phenylalanine | Eligibility Criteria | |
| LUC7L3 | Outcome Measure | |
| Maleic acid | Arm Group Description, Arm Group Label, Brief Title, Official Title | |
| Mannitol | Arm Group Description, Arm Group Label | |
| myocilin, trabecular meshwork inducible glucocorticoid response | Brief Summary, Brief Title, Official Title, Outcome Measure | |
| myotubularin related protein 11 | Outcome Measure | |
| phosphatidylserine decarboxylase | Eligibility Criteria | |
| pleckstrin and Sec7 domain containing | Eligibility Criteria | |
| prominin 1 | Brief Summary, Detailed Description, Outcome Measure | |
| protease, serine 55 | Outcome Measure | |
| Renin | Arm Group Description, Arm Group Label, Brief Title, Detailed Description, Official Title | |
| serum response factor | Outcome Measure | |
| SLPI | Eligibility Criteria | |
| Sorbitol | Brief Title, Official Title | |
| Thrombospondin-1 | Outcome Measure | |
| Transforming growth factor-beta (TGF-beta) | Outcome Measure | |
| Vascular endothelial growth factor A (VEGF) | Arm Group Description, Brief Summary, Brief Title, Detailed Description, Official Title, Outcome Measure |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Glaucoma | - | - | Marketed | USA | Topical / Drops | 29 Jul 2004 | |
| Ocular hypertension | - | - | Marketed | USA | Topical / Drops | 29 Jul 2004 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Senju Pharmaceutical | Originator | Japan |
| Senju Pharmaceutical | Owner | Japan |
| ISTA Pharmaceuticals | Market Licensee | USA |
| Alvogen Korea | Licensee | South Korea |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| Istalol | ISTA Pharmaceuticals | Glaucoma | USA |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 19 Jan 2022 | Biomarker Update | Biomarkers information updated Updated 21 Jan 2022 |
| 04 Feb 2019 | Other | Chemical structure information added Updated 04 Feb 2019 |
| 01 Jun 2015 | Company Involvement | DreamPharma Corporation has merged with KunWha Pharmaceutical to form Alvogen Korea Updated 03 May 2016 |
| 06 Aug 2014 | Company Involvement | DreamPharma Corporation has been acquired by Alvogen Updated 12 Sep 2014 |
| 06 Jun 2012 | Company Involvement | ISTA Pharmaceuticals has been acquired by Bausch & Lomb Updated 07 Jun 2012 |
| 28 Dec 2006 | Licensing Status | Timolol licensed to DreamPharma in South Korea Updated 12 May 2009 |
| 29 Jul 2004 | Phase Change - Marketed | Launched for Ocular hypertension in USA (Topical) Updated 08 Nov 2012 |
| 29 Jul 2004 | Phase Change - Marketed | Launched for Glaucoma in USA (Topical) - First global launch Updated 13 Aug 2004 |
| 10 Jun 2004 | Phase Change - Registered | Registered for Ocular hypertension in USA (Topical) Updated 08 Nov 2012 |
| 10 Jun 2004 | Phase Change - Registered | Registered for Glaucoma in USA (Topical) Updated 10 Jun 2004 |
| 29 Jul 2003 | Regulatory Status | ISTA Pharmaceuticals has received an approvable letter from the FDA for timolol in Glaucoma Updated 29 Jul 2003 |
| 30 Sep 2002 | Phase Change - Preregistration | Preregistration for Ocular hypertension in USA (Topical) Updated 08 Nov 2012 |
| 30 Sep 2002 | Regulatory Status | Senju Pharmaceutical has filed a NDA with the FDA in USA for Glaucoma Updated 14 Jan 2003 |
| 30 Sep 2002 | Phase Change - II | Phase-II clinical trials in Glaucoma in Japan (Topical) Updated 01 Oct 2002 |
| 30 Sep 2002 | Phase Change - Preregistration | Preregistration for Glaucoma in USA (Topical) Updated 01 Oct 2002 |
References
-
ISTA Pharmaceuticals' Istalol(TM) Receives 'BT' Rating From FDA, Disallowing Generic Substitution at Pharmacies.
Media Release -
ISTA Pharmaceuticals Reports Second Quarter 2003 Financial Results.
Media Release -
Alvogen Acquires Korean Dream Pharma for US$ 187 Million.
Media Release -
Dream Pharma and Kunwha Pharmaceuticals to become Alvogen Korea.
Media Release -
Bausch + Lomb Completes the Acquisition of ISTA Pharmaceuticals.
Media Release -
ISTA Pharmaceuticals Receives FDA Approval for ISTALOL(TM) for the Treatment of Glaucoma.
Media Release -
ISTA Pharmaceuticals Reports Second Quarter 2004 Financial Results.
Media Release -
ISTA Pharmaceuticals Launches ISTALOL(TM) in the United States.
Media Release -
ISTA Pharmaceuticals Announces Submission of New Drug Application For ISTALOL(TM), A Unique Formulation of Timolol.
Media Release
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