Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine

Ahlqvist, Grace P.; McGeough, Catherine P.; Senanayake, Chris H.; Armstrong, Joseph D.; Yadaw, Ajay; Ahmad, Saeed; Snead, David R.; Jamison, Timothy F.

doi:10.1021/acsomega.1c00772

Cited by 44 publications

(46 citation statements)

References 11 publications

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“…As more information becomes available, it is possible that other promising drugs such as imatinib, infliximab, or molnupiravir may be approved by the WHO if initial clinical results from preprints are confirmed in larger peer-reviewed randomized, controlled trials. A recently published study (October 2021) has found that the 5-day course of the antiviral molnupiravir taken at 800 mg BD could profitably be sold for less than US $20 per person when calculated using Panjiva API export data [ 41 ], and using raw ingredients and a synthetic process with solvent capture this could drop to below US $5 per course [ 42 ]. When we ran our own preliminary analysis using API data available in June 2021 and calculated molnupiravir\'s estimated cost of production, we found a potential cost that was more than 10× higher than the later October study.…”

Section: Discussionmentioning

confidence: 99%

Minimum Manufacturing Costs, National Prices, and Estimated Global Availability of New Repurposed Therapies for Coronavirus Disease 2019

Wang

Levi

Ellis

et al. 2021

Open Forum Infectious Diseases

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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.

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Section: Discussionmentioning

confidence: 99%

Minimum Manufacturing Costs, National Prices, and Estimated Global Availability of New Repurposed Therapies for Coronavirus Disease 2019

Wang

Levi

Ellis

et al. 2021

Open Forum Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…As more information becomes available, it is possible that other promising drugs such as imatinib, infliximab or molnupiravir may be approved by the WHO if initial clinical results from pre-prints are confirmed in larger peer reviewed RCTs. A recently published study (October 2021) has found that the 5-day course of the anti-viral molnupirivir taken at 800mg BD could profitably be sold for less than $20 per person when calculated using Panjiva API export data [41] and using raw ingredients and a synthetic process with solvent capture this could drop to below $5 per course [42]. When we ran a preliminary analysis of API Panjiva data of molnupiravir in June 2021, we found a treatment course would cost more than x10 fold higher.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Levi

Ellis

et al. 2021

Preprint

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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.

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“…Ahlqvist, Grace P et al [ 28 ] described a two-step supply-centered and chromatography-free synthesis of molnupiravir from cytidine. By undergoing transamination to yield, the final medicine product followed a selective enzymatic acylation.…”

Section: Review Of Recent Articles On Synthetic Methods Of Molnupiravirmentioning

confidence: 99%

Review on molnupiravir as a promising oral drug for the treatment of COVID-19

Zarenezhad

Marzi

2022

Med Chem Res

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During the COVID-19 pandemic, various drug candidates have been developed, molnupiravir (MK-4482 and EIDD-2801), which is a new orally anti-viral agent under development for the treatment of COVID-19, is under study in the final stage of the clinical trial. Molnupiravir enhances the replication of viral RNA mutations in animals and humans. Due to the high demand for the synthesis of this drug, it was essential to develop an efficient and suitable synthetic pathway from raw material. In this study, molecular docking analysis on molnupiravir is examined also, the mechanism of action (MOA) and the recent synthetic pathway is reported. This review will be helpful to different disciplines such as medicinal chemistry, organic chemistry, biochemistry, and pharmacology.

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Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine

Cited by 44 publications

References 11 publications

Minimum Manufacturing Costs, National Prices, and Estimated Global Availability of New Repurposed Therapies for Coronavirus Disease 2019

Minimum Manufacturing Costs, National Prices, and Estimated Global Availability of New Repurposed Therapies for Coronavirus Disease 2019

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

Review on molnupiravir as a promising oral drug for the treatment of COVID-19

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