scholarly journals Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19

2021 ◽  
Author(s):  
Junzheng Wang ◽  
Jacob Levi ◽  
Leah Ellis ◽  
Andrew Hill
Keyword(s):  
Export Price ◽  
Equitable Access ◽  
Access To Treatment ◽  
Drug Candidates ◽  
Pharmaceutical Ingredients ◽  
Current Availability ◽  
Repurposed Drugs ◽  
Inhaled Budesonide ◽  
Selection Of ◽  
List Prices

Abstract Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. Safe and effective treatments will need to be both affordable and widely available globally to be used alongside vaccination programmes. This analysis will estimate and compare potential generic minimum costs of a selection of approved COVID-19 drug candidates with available international list prices. Methods We searched for repurposed drugs that have been approved by at least one of the WHO, FDA or NICE, or at least given emergency use authorisation or recommended for off-label prescription. Drug prices were searched for, for dexamethasone, budesonide, baricitinib, tocilizumab, casirivimab and imdevimab, and sarilumab using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from a range of low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured for some treatments at very low per-course costs, ranging from $2.58 for IV dexamethasone (or $0.19 orally) and $4.34 for inhaled budesonide. No export price data was available for baricitinib, tocilizumab, casirivimab and imdevimab or sarilumab, but courses of these treatments are priced highly, ranging from $6.67 for baricitinib to $875.5 for sarilumab. When comparing international list prices, we found wide variations between countries. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Dexamethasone and budesonide are widely available and affordable, whilst monoclonal antibodies and IV treatment courses are more expensive.

scholarly journals Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19.

2021 ◽  
Author(s):  
Junzheng Wang ◽  
Jacob Levi ◽  
Leah Ellis ◽  
Andrew Hill
Keyword(s):  
Export Price ◽  
Production Costs ◽  
Equitable Access ◽  
Successful Management ◽  
Access To Treatment ◽  
Drug Candidates ◽  
Pharmaceutical Ingredients ◽  
Current Availability ◽  
Selection Of ◽  
List Prices

Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. No drug for prevention or treatment in earlier stages of COVID-19 are yet found; although several new candidates including ivermectin, dutasteride, baricitinib, budesonide and colchicine are being studied with some early promising results. Safe and effective treatments will need to be both affordable and widely available globally. Objectives This analysis will estimate and compare potential generic production costs of a selection of COVID-19 drug candidates with international list prices. Methods Costs of production for new and potential COVID-19 drugs (dexamethasone, ivermectin, dutasteride, budesonide, baricitinib, tocilizumab, sarilumab and colchicine) were estimated using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured at very low per-course costs: ranging from $2.58 for IV dexamethasone (or $0.19 orally) to $0.12 for ivermectin. No export price data was available for baricitinib, tocilizumab or sarilumab. When compared against international list prices, we found wide variations between countries. Drug API availability was generally good, with colchicine being the most available with sufficient annual API exported for 59.8 million treatment courses. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Analysed drugs are widely available and affordable, whilst IV treatment courses are more expensive.

scholarly journals 407. Minimum Manufacturing Costs, National Prices and Estimated Global Availability of New Repurposed Therapies for COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S305-S305
Author(s):  
Junzheng Wang ◽  
Jacob Levi ◽  
Leah Ellis ◽  
Andrew Hill
Keyword(s):  
Export Price ◽  
Production Costs ◽  
Access To Treatment ◽  
Pharmaceutical Ingredients ◽  
Current Availability ◽  
Recent Developments ◽  
Repurposed Drugs ◽  
Exposure Prophylaxis ◽  
The Cost ◽  
List Prices

Abstract Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. No drug for prevention or treatment in earlier stages of COVID-19 are yet found, with previously promising drugs such as hydroxychloroquine and remdesivir have been shown to be ineffective. Several new candidates are now being studied in clinical trials. Safe and effective treatments will need to be both affordable and widely available. We therefore revised our original 2020 analysis to reflect recent developments. In this update we analysed the cost of production, current national list prices, and API availability for oral and IV dexamethasone, ivermectin, colchicine, dutasteride, budesonide, baricitinib and monoclonal antibodies tocilizumab and sarilumab. Methods Costs of production for new and potential COVID-19 drugs (dexamethasone, ivermectin, dutasteride, budesonide, baricitinib, tocilizumab, sarilumab and colchicine) were estimated using an established and published methodology based on costs of active pharmaceutical ingredients (API), extracted from the global shipping records database Panjiva. This was compared with national pricing data from low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured at very low per-course costs: ranging from &2.58 for IV dexamethasone (or &0.19 orally) to &0.12 for ivermectin. No export price data was available for baricitinib, tocilizumab or sarilumab. When compared against international list prices, we found wide variations between countries. Drug API availability was generally good, with colchicine being the most available with sufficient annual API exported for 59.8 million treatment courses. A summary is shown in Table 1. Table 1. Summary of list prices, estimated production costs, and current availability of potential COVID-19 drugs selected for analysis. OD = Once daily, BD = twice per day, EUA = Emergency Use Authorisation (only to be given with remdesivir) *In most recent 12-month period. Conclusion Successful management of COVID-19 will require equitable access to treatment for all, not just those able to pay. Repurposed drugs can be manufactured at very low costs if shown to be clinically effective, and offers an affordable, widely available option for patients at all stages of the disease from pre-exposure prophylaxis to asymptotic and mild infections, through to critical care until vaccination coverage is expanded. Disclosures All Authors: No reported disclosures

scholarly journals Serotonergic Neurotransmission System Modulator, Vortioxetine, and Dopaminergic D2/D3 Receptor Agonist, Ropinirole, Attenuate Fibromyalgia-Like Symptoms in Mice

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2398
Author(s):  
Kinga Sałat ◽  
Anna Furgała-Wojas
Keyword(s):  
Pain Threshold ◽  
Intraperitoneal Administration ◽  
Unknown Etiology ◽  
Key Factors ◽  
Drug Candidates ◽  
Treatment And Prevention ◽  
Emotional Processes ◽  
Repurposed Drugs ◽  
Contemporary Medicine ◽  
Selection Of

Fibromyalgia is a disease characterized by lowered pain threshold, mood disorders, and decreased muscular strength. It results from a complex dysfunction of the nervous system and due to unknown etiology, its diagnosis, treatment, and prevention are a serious challenge for contemporary medicine. Impaired serotonergic and dopaminergic neurotransmission are regarded as key factors contributing to fibromyalgia. The present research assessed the effect of serotonergic and dopaminergic system modulators (vortioxetine and ropinirole, respectively) on the pain threshold, depressive-like behavior, anxiety, and motor functions of mice with fibromyalgia-like symptoms induced by subcutaneous reserpine (0.25 mg/kg). By depleting serotonin and dopamine in the mouse brain, reserpine induced symptoms of human fibromyalgia. Intraperitoneal administration of vortioxetine and ropinirole at the dose of 10 mg/kg alleviated tactile allodynia. At 5 and 10 mg/kg ropinirole showed antidepressant-like properties, while vortioxetine had anxiolytic-like properties. None of these drugs influenced muscle strength but reserpine reduced locomotor activity of mice. Concluding, in the mouse model of fibromyalgia vortioxetine and ropinirole markedly reduced pain. These drugs affected emotional processes of mice in a distinct manner. Hence, these two repurposed drugs should be considered as potential drug candidates for fibromyalgia. The selection of a specific drug should depend on patient’s key symptoms.

scholarly journals The Repurposed Drugs Suramin and Quinacrine Cooperatively Inhibit SARS-CoV-2 3CLpro In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 873
Author(s):  
Raphael J. Eberle ◽  
Danilo S. Olivier ◽  
Marcos S. Amaral ◽  
Ian Gering ◽  
Dieter Willbold ◽  
...  
Keyword(s):  
Binding Mode ◽  
Drug Candidates ◽  
Main Protease ◽  
Ic50 Values ◽  
Repurposed Drugs ◽  
Antiparasitic Drugs ◽  
Inhibitory Potential ◽  
Dynamics Simulations ◽  
Micromolar Range

Since the first report of a new pneumonia disease in December 2019 (Wuhan, China) the WHO reported more than 148 million confirmed cases and 3.1 million losses globally up to now. The causative agent of COVID-19 (SARS-CoV-2) has spread worldwide, resulting in a pandemic of unprecedented magnitude. To date, several clinically safe and efficient vaccines (e.g., Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca COVID-19 vaccines) as well as drugs for emergency use have been approved. However, increasing numbers of SARS-Cov-2 variants make it imminent to identify an alternative way to treat SARS-CoV-2 infections. A well-known strategy to identify molecules with inhibitory potential against SARS-CoV-2 proteins is repurposing clinically developed drugs, e.g., antiparasitic drugs. The results described in this study demonstrated the inhibitory potential of quinacrine and suramin against SARS-CoV-2 main protease (3CLpro). Quinacrine and suramin molecules presented a competitive and noncompetitive inhibition mode, respectively, with IC50 values in the low micromolar range. Surface plasmon resonance (SPR) experiments demonstrated that quinacrine and suramin alone possessed a moderate or weak affinity with SARS-CoV-2 3CLpro but suramin binding increased quinacrine interaction by around a factor of eight. Using docking and molecular dynamics simulations, we identified a possible binding mode and the amino acids involved in these interactions. Our results suggested that suramin, in combination with quinacrine, showed promising synergistic efficacy to inhibit SARS-CoV-2 3CLpro. We suppose that the identification of effective, synergistic drug combinations could lead to the design of better treatments for the COVID-19 disease and repurposable drug candidates offer fast therapeutic breakthroughs, mainly in a pandemic moment.

scholarly journals Membrane Distillation for the Production of Pharmaceutical-Grade Water—Investigation into the Application of AGMD and VMD

2021 ◽  
Vol 18 (11) ◽  
pp. 6058
Author(s):  
Cornelius Nellessen ◽  
Thomas Klein ◽  
Hans-Jürgen Rapp ◽  
Frank Rögener
Keyword(s):  
Energy Demand ◽  
Tap Water ◽  
Membrane Distillation ◽  
Pharmaceutical Products ◽  
Optimum Process ◽  
The European Union ◽  
Pharmaceutical Ingredients ◽  
Multi Stage ◽  
One Step ◽  
Selection Of

The production of pharmaceutical ingredients, intermediates and final products strongly depends on the utilization of water. Water is also required for the purification and preparation of reagents. Each specific application determines the respective water quality. In the European Union, the European Pharmacopeia (Ph. Eur.) contains the official standards that assure quality control of pharmaceutical products during their life cycle. According to this, the production of water for pharmaceutical use is mainly based on multi-stage distillation and membrane processes, especially, reverse osmosis. Membrane distillation (MD) could be an alternative process to these classical methods. It offers advantages in terms of energy demand and a compact apparatus design. In the following study, the preparation of pharmaceutical-grade water from tap water in a one-step process using MD is presented. Special emphasis is placed on the performance of two different module designs and on the selection of optimum process parameters.

scholarly journals A Dual-Sensor-Based Screening System for In Vitro Selection of TDP1 Inhibitors

Sensors ◽  
2021 ◽  
Vol 21 (14) ◽  
pp. 4832
Author(s):  
Ann-Katrine Jakobsen ◽  
Josephine Geertsen Keller ◽  
María Gonzalez ◽  
Endika Martin-Encinas ◽  
Francisco Palacios ◽  
...  
Keyword(s):  
Dna Damage ◽  
In Vitro Selection ◽  
Main Function ◽  
Screening System ◽  
Drug Candidates ◽  
Topoisomerase 1 ◽  
High Throughput Drug Screening ◽  
Dual Sensor ◽  
Selection Of

DNA sensors can be used as robust tools for high-throughput drug screening of small molecules with the potential to inhibit specific enzymes. As enzymes work in complex biological pathways, it is important to screen for both desired and undesired inhibitory effects. We here report a screening system utilizing specific sensors for tyrosyl-DNA phosphodiesterase 1 (TDP1) and topoisomerase 1 (TOP1) activity to screen in vitro for drugs inhibiting TDP1 without affecting TOP1. As the main function of TDP1 is repair of TOP1 cleavage-induced DNA damage, inhibition of TOP1 cleavage could thus reduce the biological effect of the TDP1 drugs. We identified three new drug candidates of the 1,5-naphthyridine and 1,2,3,4-tetrahydroquinolinylphosphine sulfide families. All three TDP1 inhibitors had no effect on TOP1 activity and acted synergistically with the TOP1 poison SN-38 to increase the amount of TOP1 cleavage-induced DNA damage. Further, they promoted cell death even with low dose SN-38, thereby establishing two new classes of TDP1 inhibitors with clinical potential. Thus, we here report a dual-sensor screening approach for in vitro selection of TDP1 drugs and three new TDP1 drug candidates that act synergistically with TOP1 poisons.

scholarly journals Translational and Clinical Pharmacology Considerations in Drug Repurposing for X-linked Adrenoleukodystrophy-A Rare Peroxisomal Disorder

2021 ◽  
Author(s):  
Julianne Tieu ◽  
Siddhee Sahasrabudhe ◽  
Paul Orchard ◽  
James Cloyd ◽  
Reena Kartha
Keyword(s):  
Drug Target ◽  
Drug Targets ◽  
Drug Repurposing ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Candidates ◽  
Target Patient Population ◽  
Site Of Action ◽  
Repurposed Drugs ◽  
Gait Disturbances ◽  
Spastic Quadriparesis

X-linked adrenoleukodystrophy (X-ALD) is an inherited, neurodegenerative rare disease that can result in devastating symptoms of blindness, gait disturbances, and spastic quadriparesis due to progressive demyelination. Typically, the disease progresses rapidly, causing death within the first decade of life. With limited treatments available, efforts to determine an effective therapy that can alter disease progression or mitigate symptoms have been undertaken for many years, particularly through drug repurposing. Repurposing has generally been guided through clinical experience and small trials. At this time, none of the drug candidates have been approved for use, which may be due, in part, to the lack of pharmacokinetic/pharmacodynamic (PK/PD) information on the repurposed medications in the target patient population. Greater consideration for the disease pathophysiology, drug pharmacology, and potential drug-target interactions, specifically at the site of action, would improve drug repurposing and facilitate development. Although there is a good understanding of X-ALD pathophysiology, the absence of information on drug targets, pharmacokinetics, and pharmacodynamics hinders the repurposing of drugs for this condition. Incorporating advanced translational and clinical pharmacological approaches in preclinical studies and early stages clinical trials will improve the success of repurposed drugs for X-ALD as well as other rare diseases.

scholarly journals Screening Strategies and Methods for Better Off-Target Liability Prediction and Identification of Small-Molecule Pharmaceuticals

2018 ◽  
Vol 24 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Terry R. Van Vleet ◽  
Michael J. Liguori ◽  
James J. Lynch ◽  
Mohan Rao ◽  
Scott Warder
Keyword(s):  
Data Sets ◽  
Multiple Sources ◽  
Drug Candidates ◽  
Critical Gap ◽  
Screening Strategies ◽  
Feasible Option ◽  
Stage Development ◽  
Integrated Screening ◽  
Expensive Process ◽  
Selection Of

Pharmaceutical discovery and development is a long and expensive process that, unfortunately, still results in a low success rate, with drug safety continuing to be a major impedance. Improved safety screening strategies and methods are needed to more effectively fill this critical gap. Recent advances in informatics are now making it possible to manage bigger data sets and integrate multiple sources of screening data in a manner that can potentially improve the selection of higher-quality drug candidates. Integrated screening paradigms have become the norm in Pharma, both in discovery screening and in the identification of off-target toxicity mechanisms during later-stage development. Furthermore, advances in computational methods are making in silico screens more relevant and suggest that they may represent a feasible option for augmenting the current screening paradigm. This paper outlines several fundamental methods of the current drug screening processes across Pharma and emerging techniques/technologies that promise to improve molecule selection. In addition, the authors discuss integrated screening strategies and provide examples of advanced screening paradigms.

scholarly journals Continuous one-flow multi-step synthesis of active pharmaceutical ingredients

2020 ◽  
Vol 5 (7) ◽  
pp. 1186-1197 ◽  
Author(s):  
Victor R. L. J. Bloemendal ◽  
Mathilde A. C. H. Janssen ◽  
Jan C. M. van Hest ◽  
Floris P. J. T. Rutjes
Keyword(s):  
Continuous Flow ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Flow Processes ◽  
Selection Of

This review highlights a selection of multistep continuous flow (one-flow) processes leading to the synthesis of active pharmaceutical ingredients (APIs).

Computational Design of Copper Ligands with Controlled Metal Chelating, Pharmacokinetics, and Redox Properties for Alzheimer’s Disease

2020 ◽  
pp. 1-15
Author(s):  
Diego Chaparro ◽  
Areli Flores-Gaspar ◽  
Jorge Alí-Torres
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Density Functional ◽  
Computational Design ◽  
Redox Properties ◽  
Drug Candidates ◽  
Metal Chelating ◽  
Structure Search ◽  
Copper Ligands ◽  
Selection Of

Background: Redox active metal cations, such as Cu2 +, have been related to induce amyloid plaques formation and oxidative stress, which are two of the key events in the development of Alzheimer’s disease (AD) and others metal promoted neurodegenerative diseases. In these oxidative events, standard reduction potential (SRP) is an important property especially relevant in the reactive oxygen species formation. Objective: The SRP is not usually considered for the selection of drug candidates in anti-AD treatments. In this work, we present a computational protocol for the selection of multifunctional ligands with suitable metal chelating, pharmacokinetics, and redox properties. Methods: The filtering process is based on quantum chemical calculations and the use of in silico tools. Calculations of SRP were performed by using the M06-2X density functional and the isodesmic approach. Then, a virtual screening technique (VS) was used for similar structure search. Results: Protocol application allowed the assessment of chelating, drug likeness, and redox properties of copper ligands. Those molecules showing the best features were selected as molecular scaffolds for a VS procedure in order to obtain related compounds. After applying this process, we present a list of candidates with suitable properties to prevent the redox reactions mediated by copper(II) ion. Conclusion: The protocol incorporates SRP in the filtering stage and can be effectively used to obtain a set of potential drug candidates for AD treatments.

Sign in / Sign up

Export Citation Format

Share Document