A vial of pure remdesivir. Photo: Gilead Sciences Inc/Handout via Reuters.
‘Marketism’ is the notion that markets are not a tool but an end in themselves. ‘Peoplism’ is the notion that welfare of masses is the end for which markets are a useful tool, but there can be other tools too.
When we conduct a clinical trial, we have a primary aim that we call an endpoint. For example, mortality reduction is an endpoint. Blood pressure is another type of endpoint because it’s an indirect marker of mortality. A medicine is a tool to reduce blood pressure (if it’s too high) and thus mortality.
We test new medicines so that they can get regulatory approval for marketing. During the testing, it is possible (and has happened) that a new medicine decreases BP in patients with high BP, but instead of decreasing mortality, increases it. What do we do in that case? We abandon that drug.
In the same way, if markets fail in some situations, it would be irrational to keep sticking to that tool – as if achieving marketism was the goal and not peoples’ lives.
According to some estimates, it could take up to $2 billion to bring one substance to market as a drug. Whatever be the figure, drug discovery/development is an expensive, time-consuming endeavour and most new drugs are brought to the market by companies.
Remdesivir was developed by Gilead Sciences, an American pharmaceutical company, for hepatitis C and respiratory syncytial viruses more than a decade ago but did not receive marketing approval.
It was later tested for Ebola, SARS, MERS and Marburg virus infections, and again didn’t demonstrate sufficient efficacy to be approved.
The COVID-19 pandemic has provided a new opportunity. It soon generated a lot of hype during the current pandemic and was even offered by the US president to the British prime minister in the first week of April when the latter developed COVID-19. Gilead wasn’t claiming any efficacy at that time, only saying it was a promising medicine.
On 10th of April, the New England Journal of Medicine published data of an experiment in which researchers administered remdesivir to 61 hospitalised COVID-19 patients over 10 days. They found 68% improved while 13% died. Data for eight patients was not provided. It is difficult to say based on this as to how efficacious or inefficacious the drug was because there was no control group. Nonetheless, Gilead called the results “hopeful”.
Soon, there was also a ‘leaked’ video in which an infectious disease specialist from the University of Chicago said, “The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish.” The university statement was more cautious: “Partial data from an ongoing clinical trial is by definition incomplete and should never be used to draw conclusions about the safety or efficacy of a potential treatment that is under investigation.”
Meanwhile, the share price of Gilead kept going up, from around $65 per share before the pandemic to above $80 at the moment.
No atheists in foxholes
On April 17, a Bret Stephens of the New York Times criticised “big-pharma haters” and claimed “effective diagnostic tests, therapies and vaccines … typically emerge from profit-seeking companies operating in fiercely competitive and well-regulated marketplaces.” He added, “One lesson from this pandemic is how dependent we are for our survival on an innovative and robust pharmaceutical industry. Maybe we should do more as a country to cultivate it than tear it down.”
It was a twisted logic. For one thing, is it okay to hate Big Pharma outside of a pandemic? And is it okay for a company to cling to profits at such a fraught time as this?
A few days later, articles in The Guardian and Financial Times reported a WHO report of results of a randomised, controlled clinical trial in China: 158 patients had received remdesivir and 79 received placebo. There was no difference in mortality (14% in remdesivir group v. 13% in placebo); adverse reactions to remdesivir led to its early stoppage in about 12% patients; no other details were provided. However, the results were quickly removed from the web because they had not been peer-reviewed, according to the WHO.
Gilead also has other ongoing trials of this drug. Recently, it changed its trial protocols at least in one instance, where it increased the sample size to 6,000, added more study groups and changed the primary outcome measure – a step that led to a jump in its shares even though such post hoc changes in outcome measures are not recommended, especially when they happen after looking at the now-unavailable results of a failed trial.
At the time when all these activities were going on, Gilead applied for and was granted “orphan drug” status for remdesivir by the US Food and Drug Administration, which allows greater marketing exclusivity to companies but is reserved for drugs meant to treat rare diseases. After facing criticism, Gilead asked the FDA to revoke the orphan drug status.
There are atheists in foxholes.
Blinding by ideology
Bret Stephens’s ideological blindness is absolute. His article did not even once remind people that a lot of funding based on which new drugs are developed comes from the public sector. A recent study showed government funding contributed to discovery and/pr development of every one of the 210 new drugs approved by the FDA between 2010 and 2016.
Gilead drew heavy flak a few years ago for pricing its hepatitis C virus drug sofosbuvir at $1,000 per tablet, $84,000 for the full course (Rs 75,540 and Rs 63.4 lakh respectively). Other related medicines soon followed, with excellent cure rates for hepatitis C. The company claimed that the price was justified because of the value it provides. The latter is true – but there is more to this story.
The original research that led to this fantastic medicine occurred in a publicly funded laboratory at Emory University in the 2000s, from where a start-up, named Pharmasset, emerged and was later acquired by Gilead for $11 billion in 2011 after Pharmasset demonstrated that early results with sofosbuvir were better than other drugs under development. Within three years, Gilead had earned more than three times what it spent to acquire Pharmasset, and 40-times the cost of developing these medicines.
In a tragic irony, Gilead sued the US government last week for patent infringement of its anti-HIV drug after 15 years of collaboration.
It’s not the scientists’ fault
Often times such critiques of the pharmaceuticals industry and its apologists are twisted to make them sound like criticism of scientists. Let there be no confusion: several colleagues, friends and students are currently involved in high-quality, advanced research to bring new medicines to patients. They are dedicated professionals and we should recognise and applaud them as well as the industry for a lot of good work they do.
Markets are a wonderful tool. However, we often forget that they are only tools, and that peoplism should come before marketism or profitism. Stephens never tries to explore people’s contribution to R&D, and presents a one-sided market view.
This has consequences for the future too. According to the WHO, on Dec 31, 2019, the Wuhan municipal commission reported a cluster of cases of unidentified pneumonia, and on January 12, 2020, the genetic sequence of the novel coronavirus had already been shared with the world. This publicly available information was used to market testing-kits and start development of vaccines. Now to say that it is the profit-making companies doing everything is grossly misleading. We must devise ways to ensure that the people gets their return on investment, too.
Having shown in test tubes to be useful against many viruses, remdesivir is still searching for a disease it can cure.
Samir Malhotra works at the Post-Graduate Institution of Medical Education and Research, Chandigarh.