Treatments for COVID-19 could be manufactured for $1 a day or less, and distributed through mechanisms like those used for HIV, TB and malaria, reports Polly Clayden:

First published by HIV i-Base in HTB (HIV Treatment Bulletin) on 14 April 2020.

Polly Clayden, HIV i-Base

If repurposed drugs, currently under investigation for COVID-19, show efficacy, they could be manufactured profitably at very low costs – according to an analysis published in the Journal of Virus Eradication
on 8 April 2020. [1]

As the SARS-CoV-2 pandemic grows daily, clinical trials are underway worldwide looking at potential ways to prevent new infections, treat those already infected and reduce the severity of the disease.

Results from randomised controlled trials of repurposed drugs – ie those currently indicated for other diseases so shortening the drug discovery and development timeline – are expected between May and September of this year.

Andrew Hill and colleagues – whose group have previously reliably predicted the minimum costs of drugs for hepatitis C and other diseases – calculated the costs of new potential treatments for COVID-19.

The authors used established methods to make these calculations. They estimated the minimum costs of drug production by calculating the cost of active pharmaceutical ingredients (API), added to costs of excipients, formulation, packaging and a profit margin of 10%, to calculate the price of the final finished product (FFP) – the drug ready for use.

The selected treatments were: remdesivir (previously used unsuccessfully against Ebola); favipiravir (influenza), lopinavir/ritonavir (HIV), chloroquine and hydroxychloroquine (malaria) and sofosbuvir and daclatasvir (HCV), azithromycin (pneumonia), and pirfenidone and tocilizumab (improve lung function and reduce inflammation).

Remdesivir

Remdesivir is given by IV infusion. A 10-day course of treatment is under investigation at a dose of 200 mg on the first day and 100 mg the following days.

The authors estimated the cost per treatment to be approximately $9 per person – an estimated daily cost of $0.93.

They note that costs for non-drug components associated with IV infusion were not included in this estimate:  saline, equipment (syringe, sterile water and IV lines) and staff time.

Favipiravir

Favipiravir is an oral treatment dosed at 600 mg twice daily. A 14-day course is being evaluated.

The estimated cost of production for this course is $20 or $1.45 per day.

The authors added that favipiravir was launched for sale in China in late February 2020 at a price of $231 per 14-day course.

Lopinavir/ritonavir

The standard dose of lopinavir/ritonavir is 400/100 mg oral combined pill twice daily. A 14-day course is also being evaluated.

The estimated cost for this course is $4 or $0.28 per day.

So far there has been no clear evidence of efficacy for lopinavir/ritonavir against COVID-19.

Current list prices for a 14-day course range from $503 in the US to $15 in South Africa (and available through the Global Fund to low- middle-income countries for a medium of $9).

Hydroxychloroquine and chloroquine

These old malaria treatments (since the ’50s) were calculated at 400 mg and 155 mg daily doses for 14 days of hydroxychloroquine and chloroquine, respectively.

The estimated costs were $1 per course or $0.08 per day and $0.3 or $0.08 per day for the respective drugs.

Available list prices for a 14-day course of hydroxychloroquine ranged from $19 in China to $2 in India.

For chloroquine these prices ranged from $93 in US to $0.2 in Bangladesh for a course. The authors note that the Bangladesh price was lower than their estimate and the US one might be considered an outlier (by a considerable amount as the next most expensive price for a 14-day course, in the UK, was $8).

Azithromycin

Used in small pilot studies with hydrochloroquine (and contradictory results) to prevent bacterial superinfection.

A 14-day course at a dose of 500 mg per day was calculated at $1.40 or $0.10 per day.

List prices for azithromycin range between $63 per 14-day course in the US and $5 in India and Bangladesh.

Sofosbuvir/daclatasvir

Under evaluation in Iran for people with moderate to severe COVID-19 symptoms at a daily dosage of sofosbuvir/daclatasvir 400/600 mg.

The estimated cost is $5 per 14-day course or $0.39 per day.

These drugs were launched by originator manufacturers for treatment of Hepatitis C at eye-watering prices, which have fallen significantly in recent years.

Earlier estimates of minimum price for generic production by Hill et al in 2016 were equivalent to $7.8 per 14-day course, so the new estimates represent a 6.6-fold reduction since the group’s original calculations.

Fourteen-day list prices range from $18,610 in the US and $7 in India or $6 in Pakistan.

Pirfenidone

A dose of 801 mg three times a day for four weeks is being evaluated.

The estimated cost for a 4-week course is $31 or $1.09 per day.

List prices for a 4-week course range from $9,606 in the US to $124 in Bangladesh and $100 in India for a generic version.

The authors explained that at $100, the lowest list prices are still higher than their estimate.

Tocilizumab

This monoclonal antibody is dosed as an IV infusion. Doses are based on weight (8 mg/kg) with a maximum single dose of 800 mg every 12 hours.

The authors assumed an average bodyweight of 70 kg and a single dose of 560 mg.

There were no API data available for tocilizumab – so they were unable to estimate the minimum cost of production.

List prices for 560 mg single dose varied from $3,383 in the US to $510 in Pakistan.

Several biosimilars are currently under development but these have yet to be approved and launched.

Biosimilars can offer healthcare systems the potential to lower costs significantly. The UK is expected to save up to £200–300 million a year through the uptake of better-value biological medicines.

Conclusion

The authors emphasised that we do not know yet which or any of these drugs will show benefit. But this analysis shows that if that was the case they all could be manufactured for very low prices.

Repurposed drugs might be the only option to treat COVID-19 for the next 12–18 months, until effective vaccines can be developed and manufactured at scale.

Some of the treatments are already available as generic, with prices close to the cost of manufacture for low- and middle-income countries.

Treatments for HIV, TB and malaria are distributed worldwide by the Global Fund and PEPFAR at prices close the cost of manufacture. These prices allow generic companies to make acceptable profits. The authors recommend that a similar model of drug distribution be adopted for COVID-19.

They made four recommendations to ensure that anyone with COVID-19, in any country, would be able to access the treatment they need:

  1. Treatments showing efficacy in well-powered clinical trials should be made available worldwide at prices close to the cost of manufacture.
  2. There should be parallel manufacture by at least three different companies for each product, sourcing their API from different countries. Production of drugs in a range of countries will protect us from disruption or shortages in individual countries.
  3. There should be no intellectual property barriers preventing mass production of these treatments worldwide. We need open ‘technology transfer’ so that the methods used to manufacture the key drugs can be shared with any country deciding to produce the drugs locally.
  4. Results and databases from all COVID-19 clinical trials should be fully accessible so others can learn from them. To speed up access to these drugs, countries could rely on recognition of the review and approval of key treatments by regulatory authorities in the US or Europe, or other stringent regulatory authorities. There may not be time for the normal times of regulatory review by all individual countries.

COMMENT

The authors looked at costs of production for the main treatments currently being tested in clinical trials.  These drugs could be mass produced for $1 per day, often for a lot less, and distributed through mechanisms like those used for HIV, TB and malaria.

Even remdesivir, the new potential treatment from Gilead, could be mass produced for $9 for a 10-day treatment course.  The cost of the saline (and other non-drug components) would be higher than the remdesivir, when given by IV infusion.

Some of these treatments have US list prices 100 times higher than the cost of production. The Presidential-favourite untested COVID-19 candidate is over 10 times as much in US as the UK. 

Anyone with COVID-19, in any country, should be able to access these new treatments if the prices can be kept close to production costs. 

Previous minimum cost estimates by Hill et al have been invaluable to support price negotiations for treatments for other diseases. Among many others, MSF welcomed the COVID-19 estimates. [2] “Literally every single person on earth is susceptible to this pandemic – now is not the time for price gouging and pandemic profiteering” they wrote.

At the moment, countries are becoming insular, competing for limited supplies of drugs, ventilators and PPE, in bidding wars, rather than engaging in a collaborative system for resources to be prioritised for areas of greatest need.  

References

  1. Hill et al. Minimum costs to manufacture new treatments for COVID-19. Journal of Virus Eradication. Online 9 April 2020.
    http://viruseradication.com/journal-details/Minimum_costs_to_manufacture_new_treatments_for_COVID-19/
  2. MSF press release. MSF response on COVID-19 drugs pricing study by Andrew Hill et al. 10 April 2020.
    https://msfaccess.org/pt-br/node/56576?tid=9
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