Pfizer has a head start, but the Covid-19 vaccine market is still up for grabs

Pfizer and BioNTech advanced in the race to develop a Covid-19 vaccine this week, announcing preliminary data showing 90% effectiveness. Financial markets rallied on the tantalizing prospect that a return to normality was approaching. But the advantage may be short-lived, as competitors, whose vaccines may be easier to transport or administer, are preparing to report data in the weeks and months to come. “Pfizer will probably have the first-mover advantage, but it won’t last that long,” says Damien Conover, director of health care equity research at Morningstar. “It will probably only be two or three months at the most.”

While there are winners and losers in normal drug development, and the first company to enter a particular therapeutic area often gains a significant advantage, that’s not the case with Covid-19 vaccines, says Bunny Ellerin, director of Health and Pharmaceutical Management Program at Columbia Business School. “The pandemic affects everyone. The universe of people you need to cover is huge, ”he says. “There is no single player who can provide vaccines for everyone.”

One of the main reasons the preliminary data from Pfizer was so surprising is that the mechanism the vaccine uses, messenger RNA or mRNA, has never before been approved for use in humans. Being 90% effective, even among a small number of patients in ongoing trials, is very high compared to other common vaccines. For example, the annual flu vaccine can reduce the risk of getting the flu by about 40% to 60%, depending on the year. “It is tremendously powerful for the industry,” says Ellerin. “It shows that this platform can work and will therefore be used in the future.” It also bodes well for the biotech company Moderna, which is developing a competitive mRNA-based vaccine and plans to release interim data soon.

The distribution dilemma

The downside to Pfizer’s current mRNA vaccine formulation is that it must be stored at ultra-low temperatures instead of the usual 2 to 8 ℃ (36 to 46 ℉) for many vaccines on the market. As Pfizer collects more stability data, it has determined that the vaccine can remain between 2 and 8 ℃ for up to 5 days, but longer term storage should be around -70 ℃ (-94 ℉). “There has never been a vaccine in the United States that requires that kind of storage temperature before use,” says Dr. Kelly Moore, associate director of immunization education at the Immunization Action Coalition and an external advisor to Pfizer.

This poses a unique challenge, given that there isn’t much space in the ultra-low-capacity freezer in the United States or around the world, says Prashant Yadav, an expert in healthcare supply chains and a professor at INSEAD. “The only places where we have ultra-cold chain equipment are academic medical centers, fairly large hospital systems, or some of the sites that FedEx, UPS or [the big distributors] they have created, ”he says.

The usual route for routine vaccines is to go from the manufacturer to a large distribution center, run by a company like McKesson, Cardinal or AmeriSource Bergen, which then ships them to another storage warehouse outside of major metropolitan areas, Yadav says. From there, the vaccines are shipped to doctors’ offices, pharmacies and hospitals as needed, requiring refrigerators in warehouses and at the point of care.

There are some freezers available for certain products, such as cancer drugs and clinical trial materials, but these generally run at 0 to -20 ℃ (32 to -4 ℉), which is not cold enough for Pfizer’s vaccine. “The only way to distribute will be to ship the product, either almost daily, or at least several times a week from the manufacturer to the vaccination point” for ultra-cold chain products, Yadav says.

Other vaccines in development do not need to be frozen and will only require refrigeration.

That’s Pfizer’s initial plan, storing its Covid-19 vaccines in ultra-cold storage sites in Kalamazoo, Michigan and Pleasant Prairie, Wisconsin, and then shipping them directly from there to the point of use, according to a spokesperson. Pfizer, which continues to study storage conditions at warmer temperatures, has also designed special thermal conveyors, “which can be used as temporary storage units by filling with dry ice for up to 15 days of storage.”

A Moderna spokesperson said the company expects its mRNA vaccine to be stored at -20 ℃ (-4 ℉), “which is an easier and more established protocol than deep freezing,” and close to the temperature of a home freezer. . “We expect to allow refrigerated conditions of 2 to 8 ℃ (36 to 46 ℉) for about a week,” the company said.

But other vaccines in development that use different mechanisms, such as the protein subunit vaccine that Novavax is developing, do not need to be frozen and will only require refrigeration, potentially making them easier to distribute through existing channels. The federal government’s Operation Warp Speed ​​program is providing $ 1.6 billion to support the large-scale manufacture of 100 million doses of Novavax’s candidate vaccine. The program has also provided up to nearly $ 2 billion in funding to Moderna for the development and manufacture of 100 million doses of its candidate vaccine, and has agreed to purchase up to 100 million doses of the vaccine from Pfizer, once it gets approval. regulatory, at a price of $ 1.95 billion.

In the first phase, the program “anticipates having a limited supply of COVID-19 vaccines to distribute, which should alleviate initial concerns about possible long-term storage of vaccine doses,” according to a spokesman for the Department of Health and Services. US Humans “The intent is to distribute vaccines to state-identified locations when vaccine administration can follow quickly, meaning that vaccines will often be administered before needing storage other than the container in the one who sent the vaccines. ” The effort includes the CDC, the Department of Defense, private sector companies, and state governments.

One shot too many?

One of the other logistical hurdles is that most vaccine candidates require a two-injection regimen, meaning that patients receive one injection and then have to return for a second injection around 3 weeks later. While common vaccines, like the flu, can have pre-filled syringes or single-shot doses, most Covid-19 vaccines will ship in multi-dose vials. That means that once the providers open the vial, they must use the contents within 24 hours. “If we were to wait for things to be more convenient, thousands and thousands of people would die in the meantime, and that is not a price we are willing to pay,” says Moore, who advises Pfizer.

During a pandemic, the first step is to bring a safe and effective vaccine to market, with advancements such as single injection doses in the future. The exception is Johnson & Johnson, which is one of the only companies evaluating single-dose and two-dose regimens as part of its phase 3 trial. The company has received $ 456 million in federal development funding and $ 1 1 billion for the first 100 million doses.

Covid-19 vaccines will likely need to be administered to large numbers of people at one time, so that none of the product is wasted due to temperature and multiple dose limitations. “Mass vaccination clinics are not something we normally think of for routine immunization, but it is certainly something that public health and healthcare facilities are very familiar with,” says Moore, recalling that it dates back to the 1950s, when the polio vaccine was administered. children at school. The first priority will be to vaccinate front-line workers caring for Covid-19 patients and then move to high-risk populations. The general public should set realistic expectations, as the launch will not happen overnight.

Human behavior will also be a factor in deciding who decides to get vaccinated and who doesn’t.

And even with all the planning by companies and governments, there will still be some problems down the road. On average, there is around 5-10% overall vaccine waste, due to a variety of problems, ranging from incorrect storage temperature to open multi-dose vials to not having enough patients within the given period, says Yadav, the expert. in supply chain. “Vaccine production is very much a technical feat,” he says. “But once you walk out of the Pfizer factory gate, it’s not just about the science of logistics, it starts to get into the social sciences, because human behavior is at stake.”

Human behavior will also be a factor in deciding who decides to get vaccinated and who doesn’t. The speed at which companies and the government are trying to bring Covid-19 vaccines to market means that there is not the kind of long-term data associated with other vaccines. A big unanswered question is “how well does this vaccine work to keep you from getting infected compared to how well does it work to keep you from getting sick?” says Moore.

One of the biggest problems with Covid-19 is asymptomatic spread, that is, people who show no outward signs of a viral infection but pass it on to other people. If the vaccine reduces symptoms but doesn’t stop the infection, that means communities would have to continue other protocols, such as wearing masks and social distancing, for longer than expected. It is also unclear how long the immunity will last. “The public needs to understand why vaccine manufacturers and vaccine experts think that despite this uncertainty, we think it is a good idea to go ahead with vaccinating the public anyway and not wait,” says Moore. “We will continue to collect information so that we can address those areas of uncertainty in the months and years to come, and ultimately end this pandemic.”