If a new vaccine can be developed in under a year, why not an effective antiviral drug?

An effective drug that could treat a person once infected with Covid-19 and prevent the potential serious consequences would clearly dramatically reduce the impact of the pandemic. Indeed, if there was a very effective and very safe drug, we wouldn’t need to worry about a new vaccine!  It is also reasonable to ask that as new vaccines have been developed within 12 months from start to finish, can we be similarly optimistic about new treatments?

Do we actually need a new drug?

• As the Christmas panto season happens (or not this year!), what does the story of Aladdin tell us about prospects of new drugs for Covid-19?
• At the beginning of the pandemic there was an important question to be asked about treating Covid-19: “Can any drugs already licensed for treating other viral infection or indeed other diseases, be successful against Covid-19?”
• In technical terms – can we repurpose existing drugs rather than the much longer and risker process of developing new drugs?

In this post, I review where we are up to in repurposing and point out the challenges in starting to develop completely new drugs.

What do we want an antiviral drug to do for Covid-19?

• There are two ways any antiviral drug might work- by preventing
  • the virus multiplying once it enters a human cell
  • the damage after the virus has multiplied resulting in part as a consequence of the  body’s defence mechanisms 
• As the second of these  is common to a whole range of  infections (and indeed immune diseases like rheumatoid arthritis), repurposing a range of existing drugs was worthwhile trying in Covid-19
• The best example of this was the trial of the steroid dexamethasone, which has significantly cut the death rate of seriously ill Covid-19 patients

• The rest of this post will focus on specific antiviral drugs to stop the virus multiplying. 
• These could then be given to people in the community at the first signs of infection
• How likely is it that there are such existing drugs that could do this for Covid-19?

What examples are there of drugs that stop other viruses multiplying?

• The best example is in HIV/AIDS. Indeed, the so called anti-retroviral treatments are the mainstay of AIDS management (there is no vaccine for this infection) and have dramatically improved the outcome
• Actually, there are around 24 drugs that stop the HIV virus multiplying
• There need to be so many as patients get resistant to individual drugs and combinations of different agents work better than single drugs

• You may remember during the Swine Flu H1N1 epidemic there was much enthusiasm for the antiviral drugs Tamiflu and Relenza that we’re widely prescribed in primary care
  • In truth the infection turned out to be not as serious as was feared
  • The only difference was a modest reduction in the number of days people felt ill for and indeed recent analyses have suggested they weren’t that effective 
• This all suggests that antiviral drugs make sense as a concept but there was no evidence that drugs which worked for one virus would necessarily work for other viruses

What about using existing antiviral drugs for Covid-19?

• Lots of have been tried!
• There are a vast number of trials investigating a whole range of existing antiviral drugs for Covid-19
• I searched the available databases yesterday and found this!

• The only drug thus far with any positive data is remdesivir
  • There was initial enthusiasm for this drug as a specific antiviral agent for Covid-19 19
  • It had been developed for use against other corona viruses eg  SARS
  • Some data suggested it could make a modest difference to how long people had symptoms 
  • The USA was very enthusiastic and, looking after their own interests, went out shopping!
  • Although there have been many trials, the most recent data suggest the benefit from remdesivir is minor and it is not a candidate for widespread use

How easy will it be to develop a new drug from scratch?

It is simplest to divide up the process into stages:

• The early laboratory work for identifying a possible drug
• Testing the drug in animals
• Testing the drug in humans

• There is a considerable drop out at each stage (one estimate is that only 0.5-1% of all drugs  tested in animals end up being marketed for human use)
• The full process takes on average 10-15 years
• What it costs is obviously variable, but a reasonable average for recently licensed  drugs is between $1-2bn
• Developing drugs is a risky business!

What are the risks?

There are clinical and commercial risks.  I have put these in a reasonably sensible order, but for example evidence of harm can emerge at any stage, which would at that point stop the drug being developed further or sold

• Drug doesn’t work
• Drug works but proves to be harmful
• Early investors lose confidence and development stops
• Drug works but gets overtaken by better/cheaper drugs
• Technical problems in production etc
• Disease stops being a problem so sales plummet

Who takes the risk?

• Conventionally this has been the big pharmaceutical companies
• However much more common these days is for ‘big pharma’ to enter into the process some way down the line and pay a reasonable premium for a license to develop a drug further 
  • After university researchers have shown there may be a promising future for something they have discovered
  • When a small biotech company, perhaps set up by a university specifically to further develop their discovery, has shown benefit in animal testing
• To get to the stage, individual researchers, universities and small companies may seek external speculative investors or use their own funds (including researchers remortgaging their own homes!)

Should this not be different for a global pandemic like Covid-19? 

• It has been easy getting billions for vaccine development 
• By contrast, governments and other organisations have only funded $millions (not billions) into research for new drug treatments
• There has to be some shared risk/reward for companies to make the size of investment that is needed

Is there any possibility of speeding up/making the development process cheaper and quicker ?

• Again, the short answer is that the pace of change in drug development is staggering
• Use of artificial intelligence (* see my post on protein structures) has meant that the very lengthy development stages can be reduced in time and screen thousands of potential drugs very quickly so that clinical development can focus on the most likely 
• The clinical testing period which has up to now been say 5-10 years can also be reduced as has been demonstrated by the speed at which vaccines have been brought to market
• There is one major difference between vaccines and other drugs in that the mechanism of vaccines – to enhance the body’s production of its own antibodies – is generally known to be successful and safe
• For drugs designed for new treatment, this is more speculative

*https://makingsenseofcovid19withs.com/2020/12/08/is-this-the-greatest-breakthrough-in-medical-science-for-a-generation

Conclusion

• It would have been great to have reached the end of this difficult year with exciting news of a successful new antiviral drug to match the success of vaccines
• Of course, if the vaccines are successful and provide long term protection, then new treatments may not be needed
• However, we should be reassured that such development is happening (albeit more slowly) but also could make us better able to cope with the next viral pandemic

And finally!

This will be my last post this year.  Thanks for all the positive comments and the interest across so may countries.  Hopefully our governments will be better able or willing to ‘follow the science’ in 2021!

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