For all problems with the US health system, innovation is the only area where the country excels. The U.S. drug industry has been the gold standard for the rest of the world, as has the federal agency that regulates it, the FDA. The country’s intellectual property laws and drug approval process are purportedly designed to reward breakthrough therapies and companies that can provide years of monopolies, new treatments and treatments.
Still, the coronavirus crisis has become a major test of that premise, ending the pandemic and returning to normal, depending on the rapid development of vaccines or treatments by scientists and biopharmaceutical companies. The next phase of the crisis is highly dependent on one question: where is the innovation?
The good news is that U.S. drug manufacturers have rapidly stepped up their work on Covid-19. They are repurposing and combining existing drugs in the hope that the right mixture can effectively treat coronavirus infections in people who already have it. At the same time, they are trying to find a vaccine that will never make most people sick from the virus, and there is some (measured) optimism that a coronavirus vaccine can be delivered in record time, as Vox’s German Lopez reported.
But these positives are supported by two inevitable negatives. First, antiviral research has become one of the most neglected areas in pharmaceutical development. There are not many incentives for companies to pursue this. The work is time consuming, with an uncertain and unstable market. Other, easier ways offer greater financial benefits, even if they do not have the same medical efficacy as treatments for unexpected viral outbreaks to which most of the world’s population is still vulnerable.
Second, the innovation industry’s Covid-19 work has also been hampered by a disorganized federal government. Both of them don’t know what to turn their attention to, and they don’t know who to partner with if they have ideas for development because there is no overarching federal strategy. Only now, over 1 million confirmed U.S. cases and 80,000 pandemic deaths, is the Trump administration appoint a former pharmaceutical director and venture capitalist to oversee the development of therapeutics – someone with no previous government experience.
Drug manufacturers have moved quickly to treat and ultimately prevent Covid-19. That is a testament to American innovation. But because of the market we’ve built for drug development and with the federal government behind the wheel, we’re still a step behind in the race for healing.
Covid-19 is not the latest epidemic or pandemic. Viruses aren’t the only threat, ”Robin Feldman, director of the UC-Hastings Center for Innovation, told me. “Unless we think about our long-term incentive structure, we will always be reactive. We never lead the way. “
Drug manufacturers are working on short-term treatments and long-term vaccines
For the immediate coronavirus crisis, it must be strongly argued that pharmaceutical companies act swiftly in the interests of public health and rationally towards their own market-driven goals.
“I would say the biopharmaceutical industry is actually doing quite well in this epidemic,” Derek Lowe, who writes about drug discovery for Science, said by email, “but there is an expectation problem.”
The fastest way to find a new treatment for Covid-19 is to use two agents that are already available to us: existing drugs and the antibodies of people infected with and survived with the coronavirus.
Most media coverage went to the first category – hydroxychloroquine, touted by President Trump and his allies, but not proven in trials, and then brake desivir, which has shown promise but remains a work in progress – which may explain the expectation issue that Lowe describes.
“Reuse of drugs is receiving a lot of attention, but the successes are few. It usually doesn’t work, ”said Lowe. “And it usually won’t work against the coronavirus either – I’ll be very happy if some of the existing drugs can help a bit, keep some people out of the ICU or like fans, but I think that’s all we can expect.”
The more promising avenue for prompt treatment, he said, is “monoclonal antibodies.” In short, like STAT explainedthat is, taking blood plasma from people infected with the coronavirus who have developed immunity (i.e. antibodies that fight the disease) and then isolate and inject antibodies into infected patients in need of treatment. It is not waterproof – a recent early trial targeting critically ill patients still had a 15 percent death rate – but it appears to be the most promising short-term therapy.
Those efforts were largely led by US biopharmaceutical companies (Regeneron, Vir Biotechnology) or by large international companies such as GlaxoSmithKline and AstraZeneca that have a large US presence and collaborate with other US companies or organizations.
Knowing that drug manufacturers are also working on a Covid-19 vaccine, which would effectively eliminate the need for other treatments, it makes both medical and business sense for the biopharmaceutical industry to provisionally focus on these opportunities in pursuit of effective treatment the vaccines are put on the market.
“That’s the fastest way, the way to get something to market as soon as possible,” said Rachel Sachs, a law professor who studies innovation policy at Washington University in St. Louis.
The current record for vaccine development, from start to finish, is four years. If we’re lucky, we may be able to halve that time for the Covid-19. But producing a ‘de novo’ treatment as Lowe called it – a truly new therapy, hitherto unknown to science – takes even longer.
So this two-track approach makes sense now, as the coronavirus is already spreading across the U.S. and taking its toll. But taking a step back shows that America hasn’t set up a market that rewards companies for anticipating this outbreak – or the next.
Pharmaceutical companies don’t have many incentives to prepare for the next pandemic
Pharmaceutical companies are actually doing the kind of work they are doing for Covid-19 right now: reusing or modifying drugs for new indications. According to Feldman’s research, nearly 80 percent of drugs associated with new patents, is actually a variation of something that already existed, either slightly modified or used in conjunction with another therapy.
That is useful. Drug manufacturers have decades of data on treatments that have been around for a long time. They know more about the risks and side effects than for anything new. That helps them make medicines that can be used more safely.
But the attention and resources devoted to repurposing old drugs detract from pursuing new therapies that would be real breakthroughs, exponential advances in science. Feldman describes innovation as “value above pearls”.
“It is rare, it is beautiful, it is surprising, it is something beautiful,” she said.
But that kind of innovation costs time and money without a certain payout. It’s easier and cheaper to modify existing products to slightly improve their effectiveness or to modify them to treat another condition.
“I’m afraid our system is not well prepared for it,” she said. “It’s all about the incentives. Our incentives are not well focused.”
She pointed to the shift from research to antibacterial resistance and drug development, even though researchers did anticipate Millions of deaths worldwide every year for decades to come as bacteria have become resistant to the drugs we are already fighting.
Drug manufacturers are currently paying a lot of attention to end-stage cancer because they can take advantage of the orphan drug designation and other competitively beneficial policies, while Feldman argued that chronic conditions are undervalued. Looking at it from a social perspective, the latter clearly has more value than the former – yet that is not necessarily what our innovation system is designed to reward.
Or look at the antiviral space, which is most relevant to the coronavirus response.
Antiviral research investments have traditionally not been a priority for the major drug manufacturers. The Wall Street Journal reported Pfizer had to re-establish its antiviral research department for its Covid-19 work because the unit was disbanded in 2009. Novartis ended up his antiviral and antibacterial research in 2018. A systematic review of the past 30 years of antiviral research showed that at the time “only a few drugs were approved to treat acute viral infections”.
“Antibiotics and antivirals are both areas where many new drugs have not yet been developed, because the economic incentives do not justify significant R&D in this area,” Caroline Pearson, senior fellow at NORC-University of Chicago, recently told me.
As long as these stimulus structures persist, Feldman warned, we will never be at the forefront of fighting the next pandemic. She said the US should ask, “What is valuable and what should we encourage people to do?”
We can improve drug development, but we need a competent authority
There are many ideas to better stimulate drug development and better reward companies for the kind of treatments we want. Most of them fall under the broad heading ‘value-based prices’: companies pay for the social benefits that their treatments offer.
“If you have a vaccine that completely stops a widespread disease,” said Feldman, “it should be extremely valuable.”
There is a similar concept known as Advanced Market Obligations developed by Harvard economist Michael Kremer over the past decade.
The bottom line is simple: a government or other entity (the first AMC was a joint venture between five countries and the Gates Foundation) agrees to pay a fixed dollar amount for a product, such as a vaccine, before ever on the market. The price would presumably be high enough to let a company know that it can recoup investments regardless of the actual number of sales eventually made.
“The idea was that if we designed a program to pay a certain amount upfront, it would encourage companies to develop these products,” said Sachs.
In summary, there are plenty of options for us. But they need a federal government with the will and ability to implement them. That’s what was seriously lacking in the Covid-19 response.
“I think one of the problems with innovation has been the extremely disorganized response from the federal government. As far as I’m concerned, the CDC, the NIH, HHS and the FDA were all different levels of bad during this crisis, ”said Lowe. “The failed testing regime in the beginning, the chaotic test approvals since then, the problems that are clearly emerging [former US vaccine chief Rick] Bright’s whistleblower complaint: it’s a mess. “
The federal government cannot just spend money and speed up drug approval. It can convene scientists, drug manufacturers and regulatory officials. It can lubricate the wheels of American innovation and hopefully accelerate the breakthroughs everyone wants to see.
But it didn’t really happen. The Trump administration announced Operation Warp Speed at the end of April with the aim of rapidly developing a vaccine. That had been in the pandemic for months, and the White House only chose someone to supervise in mid-May. The new head of that operation, Moncef Slaoui, is a former pharmaceutical director who has no previous government experience, unlike some of the other contenders for the role, such as Politico reported.
The experts I spoke to viewed the federal response, and in particular the work to accelerate innovation, largely as a missed opportunity.
“To focus the country, to focus the NIH, to focus private sector investment on a particular challenge that American ingenuity can overcome, there is an opportunity to do that here that is not widely believed,” said Sachs.
So, for now, we have to wait for the treatment or cure that can really bring the coronavirus crisis to an end.