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Oxipurinol - XORTX Therapeutics

Drug Profile

Oxipurinol - XORTX Therapeutics

Alternative Names: Oxypurinol - XORTX; XORLO; XRx 101; XRx-008

Latest Information Update: 26 May 2020

At a glance

  • Originator XORTX Pharma
  • Developer XORTX Therapeutics
  • Class Anti-ischaemics; Antigouts; Pyrazoles; Pyrimidines; Small molecules; Urologics
  • Mechanism of Action Xanthine oxidase inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    No
  • New Molecular Entity No
  • Available For Licensing Yes

Highest Development Phases

  • Phase II/III Autosomal dominant polycystic kidney disease
  • Research Acute kidney injury; Acute lung injury; COVID 2019 infections

Most Recent Events

  • 19 May 2020 XORTX Therapeutics plans to submit IND Application for XRx-101 for COVID-2019 infections
  • 16 Mar 2020 Early research in Acute kidney injury in USA (unspecified route)
  • 16 Mar 2020 Early research in Acute lung injury in USA (unspecified route)

Development Overview

Introduction

A proprietary reformulation of oxipurinol (XRx 008), a xanthine oxidase inhibitor, is being developed by XORTX Therapeutics (previously XORTX Pharma) for the treatment of autosomal dominant polycystic kidney disease (ADPKD), and XRx-101 (a new formulation of oxypurinol) for acute kidney and lung injury accompanying coronavirus infection and specifically for the COVID-2019 infections. Other potential indications include hereditary hypouricaemia and diabetic nephropathy. XORTX’s approach is to use its product, called XORLO, to inhibit the excessive accumulation of serum uric acid (SUA), a key modulator in the pathology of these diseases. While uric acid is essential in the excretion of excess nutrients, SUA at high levels through a newly discovered mechanism can cause disease, such as accelerated kidney injury in patients with ADPKD. The PKD Foundation is providing scientific expertise to XORTX for the treatment of ADPKD. The FDA approved the compassionate use of oxipurinol in patients with gout who could not tolerate allopurinol. There are currently no SUA lowering agents approved for treatment. Clinical development for autosomal dominant polycystic kidney disease is underway in the US. Early research for ongoing in the US for acute lung injury, acute kidney injury and COVID-2019 infections.

XRx 101 is a new formulation of oxypurinol for the treatment of acute kidney injury, acute lung injury and COVID-2019 infections. The company believes that XRx 101 has the potential to treat COVID-2019 infections based on its anti-viral properties. Early research development in COVID-209 is underway in the US.

In January 2018, APAC Resources merged with XORTX Pharma and subsequently changed its name to XORTX Therapeutics [1] .

As of January 2020, Oxipurinol is available for licensing [2] .

Company Agreements

In April 2020, XORTX Therapeutics entered into a manufacturing agreement with Lonza Pharma & Biotech for the active pharmaceutical ingredient for XRx-101 (Oxypurinol) and XRx-008. Stepwise manufacturing of Oxypurinol to support the drug development and clinical trial process is expected to commence in May 2020. LONZA will also perform formulation work and provide clinical supplies for future clinical trials in both programs. [3] [4]

Key Development Milestones

Autosomal dominant polycystic kidney disease: As of April 2020, XORTX Therapeutics advanced documents related to orphan drug designation for oxipurinol to complete filing with the US FDA for the treatment of progressive kidney disease due to autosomal dominant polycystic kidney disease [5] .

In November 2018, XORTX Therapeutics received a response letter from the US FDA regarding an orphan drug designation application filed by the company for oxipurinol for the treatment of autosomal dominant polycystic kidney disease [6] . In September 2018, XORTX Therapeutics submitted an application for the Orphan Drug Designation status to the US FDA [7] .

As of April 2018, XORTX Therapeutics is conducting a phase II/III trial for autosomal dominant polycystic kidney disease under a special protocol assessment (XORTX Therapeutics pipeline, April 2019) [8] [9] .

In June 2018, XORTX Therapeutics in collaboration with Cato Research (also known as Cato Clinical Research) filed a pre-IND meeting request letter with the US FDA for the phase II trial of oxipurinol for the treatment of ADPKD. The request, supported by pre-IND documents, initiated a process for communication and discussion with the FDA regarding the phase II trial, defining the path for the clinical development and marketing approval of oxipurinol [10] . In August 2018, XORTX Therapeutics and Cato Clinical Research announced that the companies have submitted all the necessary pre-IND meeting documents with the FDA for the scheduled pre-IND meeting with US FDA on September 20th, 2018 [11] . In October 2018, the company reported a major revision in the development plan of oxipurinol which included manufacturing, formulation, non-clinical study plans and development strategy comprising of separate phase II and phase III clinical trials, followed by marketing application. The discussions with the FDA also suggested a substantially shorter path for marketing approval. The outcome of the pre-IND meeting with the US FDA included filing of an IND application, to characterise the bioavailability and pharmacokinetics of oxipurinol in advancing clinical studies in humans, to complete the orphan drug designation process and to conduct a single pivotal phase II/III clinical trial. The company intends to seek a special protocol assessment (SPA) from the US FDA to help in a design, endpoints and statistical analysis of a pivotal phase II/III trial to support the marketing approval [12] .

Earlier, XORTX Therapeutics had reported that phase II development of oxipurinol (XORLO) for the treatment of autosomal dominant polycystic kidney disease was planned for 2016 [13] . The company will investigate the first licensing or acquisition opportunity upon completion of the phase II development.

Several investigator-sponsored phase II trials showed that decreasing and maintaining SUA levels can suppress weight gain and decrease blood pressure, slow progression of blood vessel and kidney injury in patients with high SUA.

XORTX had planned to conduct a phase II trial of the product for the treatment of hereditary hypouricaemia in 2016.

Prior to February 2016, XORTX Pharma initiated a phase I study to evaluate oxipurinol for the treatment of patients with autosomal dominant polycystic kidney disease in the US (XORTX Pharma pipeline, February 2016 and June 2017).

Acute kidney injury, Acute lung injury and COVID-2019 infections

In May 2020, XORTX submitted Coronavirus Treatment Accelerated Program (CTAP), a development and data plan regarding a COVID-19 package and received guidance to submit a pre-IND package for review [4] .

XORTX has also initiated discussions with the US Medical Countermeasures Group associated with the U.S. Government’s Biomedical Advanced Research and Development Authority (BARDA) and separately with the National Institute of Health (NIH). These communications with BARDA and NIH are expected to further aid development of XORTX’s XRx-101 program [4] .

In March 2020, XORTX Therapeutics announced that it is developing the use of XRx 101 (a new formulation of oxypurinol) for the treatment of acute kidney injury, acute lung injury and COVID-2019 infections. The company believes that XRx 101 has the potential to treat COVID-2019 infections based on its anti-viral properties. The rationale was made based on various in vivo studies showing that xanthine oxidase inhibition may confer suppression of viral infection and decrease symptoms of coronavirus COVID-19 infection and importantly improve survivability, and most importantly to protect the kidneys from AKI. The company also announced that it has received an approval letter from the US FDA to accelerate the development of oxypurinol for the treatment of acute kidney injury, acute lung injury and COVID-2019 infections [4] [14] .

Financing information

In January 2020, XORTX Therapeutics announced the re-pricing of private placements previously announced in April 2019. The company intends to raise approximately $US5 million and the proceeds will be used to advance development of oxipurinol for polycystic kidney disease and XRx 221 [see Adis Insight Drug profile800045135] type 2 diabetic nephropathy (a phase IIb ready programme) including operations and ongoing licensing discussions [15] [2] .

XORTX raised $US1.5 million in Series A financing with proceeds allocated for the management of phase II development of XORLO.

Patent Information

In March 2020, XORTX Therapeutics filed new intellectual property rights for XRx 101 for the treatment of respiratory and kidney disease due to viral infetions [14] .

In 2014, XORTX Therapeutics filed a patent application with Patent Coorperation Treaty (PCT) for a formulation of Oxypurinol XRx 008 [3] .

Drug Properties & Chemical Synopsis

  • Formulation unspecified
  • Class Anti-ischaemics, Antigouts, Pyrazoles, Pyrimidines, Small molecules, Urologics
  • Target Xanthine oxidase
  • Mechanism of Action Xanthine oxidase inhibitors
  • WHO ATC code

    J05A-X (Other antivirals)

    M04A-A (Preparations inhibiting uric acid production)

    R07A (Other Respiratory System Products)

  • EPhMRA code

    J5B9 (Antivirals, others)

    M4A (Anti-Gout Preparations)

    R7X (All Other Respiratory System Products)

  • Chemical name 1H-Pyrazolo[3,4-d]pyrimidine-4,6-diol
  • Molecular formula C5 H4 N4 O2
  • Chemical Structure
  • CAS Registry Number 2465-59-0

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Acute kidney injury in COVID-19 patients - Research USA unspecified / unspecified XORTX Therapeutics 16 Mar 2020
Acute lung injury in COVID-19 patients - Research USA unspecified / unspecified XORTX Therapeutics 16 Mar 2020
Autosomal dominant polycystic kidney disease - - Phase II/III USA unspecified / unspecified XORTX Therapeutics 03 May 2019
COVID 2019 infections - - Research USA unspecified / unspecified XORTX Therapeutics 16 Mar 2020

Commercial Information

Involved Organisations

Organisation Involvement Countries
XORTX Pharma Originator Canada
XORTX Therapeutics Owner Canada
PKD Foundation Collaborator USA
Cato Research Collaborator USA

Licensing Availability

Licensing Organisation Available Indication Available Phase Region Date
XORTX Therapeutics - Unspecified - 31 Jan 2020

Future Events

Expected Date Event Type Description Updated
29 Feb 2020 Trial Update XORTX Therapeutics plans a pivotal phase III trial for Autosomal dominant polycystic kidney disease in February 2020 [8] 03 May 2019
10 Sep 2018 Regulatory Status XORTX Therapeutics plans a pre-IND meeting with US FDA for discussions related to a phase II trial of oxipurinol for treatment of Autosomal-dominant polycystic kidney disease in September 2018 [10] 30 Oct 2018

Development History

Event Date Update Type Comment
19 May 2020 Regulatory Status XORTX Therapeutics plans to submit IND Application for XRx-101 for COVID-2019 infections [4] Updated 26 May 2020
16 Mar 2020 Phase Change Early research in Acute kidney injury in USA (unspecified route) [14] Updated 08 May 2020
16 Mar 2020 Phase Change Early research in Acute lung injury in USA (unspecified route) [14] Updated 08 May 2020
16 Mar 2020 Patent Information XORTX Therapeutics files new intellectual property rights for XRx 101 for the treatment of respiratory and kidney disease due to viral infection [14] Updated 18 Mar 2020
16 Mar 2020 Phase Change Early research in COVID-2019 infections in USA (unspecified route) [14] Updated 18 Mar 2020
16 Mar 2020 Regulatory Status XORTX Therapeutics plans to submit IND Application for XRx-008 for phase III trial in Autosomal dominant polycystic kidney disease [14] Updated 18 Mar 2020
16 Mar 2020 Regulatory Status XORTX Therapeutics receives approval letter from the US FDA for accelerating development of XRx 101 in COVID-2019 infections [14] Updated 18 Mar 2020
31 Jan 2020 Licensing Status Oxipurinol is available for licensing as of 31 Jan 2020 [2] . Updated 11 Feb 2020
03 May 2019 Regulatory Status XORTX Therapeutics plans to submit New Drug Application for XRx-008 for Autosomal dominant polycystic kidney disease [8] Updated 03 May 2019
30 Apr 2019 Phase Change - II/III Phase-II/III clinical trials in Autosomal dominant polycystic kidney disease in USA (unspecified route) (XORTX Therapeutics pipeline, May 2019) [8] Updated 03 May 2019
29 Apr 2019 Trial Update XORTX Therapeutics plans a pivotal phase III trial for Autosomal dominant polycystic kidney disease in February 2020 [8] Updated 03 May 2019
28 Mar 2019 Phase Change - No development reported No recent reports of development identified for phase-I development in Autosomal-dominant-polycystic-kidney-disease in USA Updated 28 Mar 2019
26 Nov 2018 Regulatory Status XORTX Therapeutics received response letter from the US FDA for the orphan drug designation application for oxipurinol in Autosomal dominant polycystic kidney disease [6] Updated 28 Nov 2018
26 Nov 2018 Trial Update XORTX Therapeutics plans a phase II/III trial for Autosomal dominant polycystic kidney disease [6] Updated 28 Nov 2018
23 Oct 2018 Regulatory Status XORTX Therapeutics announces intention to submit NDA to the US FDA for Autosomal dominant polycystic kidney disease (ADPKD) [12] Updated 30 Oct 2018
23 Oct 2018 Regulatory Status XORTX Therapeutics intends to seek a special protocol assessment (SPA) from the FDA for its pivotal phase II/III trial for Autosomal dominant polycystic kidney disease (ADPKD) [12] Updated 30 Oct 2018
23 Oct 2018 Regulatory Status XORTX Therapeutics intends to file an IND application with the US FDA for Autosomal dominant polycystic kidney disease (ADPKD) [12] Updated 30 Oct 2018
10 Sep 2018 Regulatory Status XORTX applies for Orphan Drug status in Autosomal dominant polycystic kidney disease in USA [7] Updated 11 Sep 2018
08 Jun 2018 Regulatory Status XORTX Therapeutics plans a pre-IND meeting with US FDA for discussions related to a phase II trial of oxipurinol for treatment of Autosomal-dominant polycystic kidney disease in September 2018 [10] Updated 30 Oct 2018
08 Jun 2018 Trial Update XORTX Therapeutics plans a phase II trial of oxipurinol for treatment of Autosomal-dominant polycystic kidney disease [10] Updated 24 Jul 2018
08 Jun 2018 Regulatory Status XORTX Therapeutics and Cato Research file a pre-IND meeting request letter with the US FDA for Autosomal-dominant polycystic kidney disease [10] Updated 13 Jun 2018
10 Jan 2018 Company Involvement APAC Resources merged with XORTX Pharma and subsequently changed its name to XORTX Therapeutics Updated 16 Jan 2018
15 Feb 2016 Phase Change - I Phase I trials in Autosomal-dominant polycystic kidney disease in USA (unspecified route) Updated 15 Feb 2016
31 Dec 2014 Patent Information XORTX Therapeutics files for patent protection with Patent Cooperation Treaty (PCT) for XRx 008 [3] Updated 07 May 2020

References

  1. APAC Resources Inc. and XORTX Pharma Corp. Announce Closing of Reverse Take-over, Financing, Consolidation and Name Change.

    Media Release
  2. XORTX Announces Re-Pricing of Private Placement.

    Media Release
  3. XORTX Appoints Lonza for GMP Manufacturing and Formulation of XRx-101 (Oxypurinol) for Coronavirus / COVID-19 Clinical Trials.

    Media Release
  4. XORTX Provides Program Update Regarding XRx-008 for ADPKD and XRx-101 for Coronavirus / COVID-19 Programs.

    Media Release
  5. XORTX Provides Overview and Update of Key Activities.

    Media Release
  6. XORTX Receives FDA Response onOrphan Drug Designation Application.

    Media Release
  7. XORTX Announces Submission of Orphan Drug Designation Application.

    Media Release
  8. XORTX Provides Overview and Announces $5 Million Financing to Advance Clinical Trials.

    Media Release
  9. A Phase II/III trial of XRx-008 in autosomal dominant polycystic kidney disease patients

    ctiprofile
  10. XORTX Announces Filing of FDA pre-IND Meeting Request Letter.

    Media Release
  11. XORTX Submits FDA pre-IND Meeting Documents.

    Media Release
  12. XORTX Announces Revision to Polycystic Kidney Disease Clinical Development Plan.

    Media Release
  13. A phase II trial of oxipurinol in autosomal dominant polycystic kidney disease

    ctiprofile
  14. XORTX Launches XRx-101, A New Program to Treat Coronavirus COVID-19 Infection.

    Media Release
  15. XORTX Announces First Tranche Closing of Non-Brokered Private Placement.

    Media Release
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