May 21, 2024

Vaccines are often held up as one of the greatest healthcare achievements, right up there with sanitary systems that supply clean water, antisepsis in surgery and randomized clinical trials for identifying the safety and efficacy of new treatments.

But as a Biotechnology Innovation Organization (BIO) report makes abundantly clear, investment in vaccine research lags woefully behind investment in other areas of healthcare, factoring out the anomalous surge of funding in 2020 and 2021 that led to the development of COVID-19 vaccines.

“You see in some years only $100 million of venture capital investment across the whole industry,” says David Thomas, M.S., senior vice president of industry and analysis at BIO and a co-author of the report. “You compare that [with individual] companies that get hundreds of millions of dollars in our space. It really does stand out for lack of investment.”

Some of the suggestions in the report for luring more investment into vaccine development include broadening coverage so even people without insurance have no out-of-pocket costs, revamping the CDC so it has more expertise on subpopulations and a better understanding of vaccines in development and adding an FDA designation of “platform technologies” that could be used to generate multiple vaccines. The mRNA methods for developing vaccines is an example of a platform technology.

A platform designation would help with the “one-bug, one-drug” problem in vaccine development, says Phyllis Arthur, MBA, senior vice president of infectious diseases and emerging science policy at BIO. Vaccines tend to be specific to a particular pathogen, even to particular strains of a continually evolving pathogen, Thomas explains. “You can’t take a vaccine you made and try it on something else, whereas if you make a breast cancer drug and it fails, you can go on and try it in [a different type of] cancer and then sometimes find that it works,” he says.

The 41-page report, titled “The State of Innovation in Vaccines and Prophylactic Antibodies for Infectious Diseases,” was published in December 2023. Chock full oftables and charts, it outlines the investment trends in vaccines, makes some observations about reasons for the relatively low level of investment and compares the probability of successful development of a vaccine to nonvaccine biologics and small molecules. There are also pages of results from pipeline reports covering vaccines for infectious diseases overall, RNA viruses, DNA viruses, bacterial pathogens, parasitic pathogens and novel combinations, such as those combining vaccines against COVID-19, flu and respiratory syncytial virus.

Current development

Vaccines are immunologic provocateurs. As the BIO report explains, they use part of an intact pathogen or part of one to “actively train” the immune system to fend off a pathogen. They are distinct from prophylactic antibodies that involve provisioning the body with antibodies to fight off the pathogen rather than provoking the immune system to make them itself. The earlier prophylactic antibodies were used against diphtheria and tetanus and were derived from infected horses.

There are currently 34 vaccines for unique pathogens approved in the U.S. or globally. They have been improved, but the vaccines against smallpox and cholera date back to the 19th century. But there is a long list of infectious diseases for which there is no vaccine, perhaps most notably HIV, despite 40 years of trying. Gonorrhea, norovirus and chlamydia are also on the roster of scourges with no vaccines.

By BIO’s count, using the Biomedtracker and Pharmaprojects databases, the global vaccine pipeline includes 249 company-sponsored clinical trials of novel vaccines, with the largest proportion, 48%, in phase 1 trials. Many developers have shut down COVID-19 trials, but there are still 69 active COVID-19 trials, and they account for 28% of the vaccine trials in BIO’s tally.

One theme of the BIO report is the shallowness of vaccine development. Only 10% of the infectious diseases have 10 or more active vaccine development programs, and just 20% have five or more, the report says. For many pathogens, there is a single vaccine in development, according to BIO, including West Nile virus, chlamydia, gonorrhea and Lyme disease.

Early-phase drug and vaccine development is always something of a gamble, and the odds of success — a drug or vaccine going from testing in a phase 1 trial to FDA approval — are long. Interestingly, the BIO report says that the odds were slightly better for vaccines (11%) than for nonvaccine biologics (7.9%) and small molecules (5.6%) for the period 2013 to 2022. Relative numbers can be misleading, however, because the absolute number of vaccines in development is so much smaller than the number nonvaccine biologics or small molecules.

Investment trends

According to the BIO report, venture capital investment in companies with vaccines for infectious diseases as their lead products added up to
$6.5 billion worldwide from 2013 to 2022, of which $2.2 billion was in the U.S. That accounted for just 3.4% of the $190 billion raised worldwide for biopharmaceutical companies. In contrast, companies with oncology products as their lead candidates raised approximately $72.6 billion over the same period, or 38% of the total and 12 times the amount raised for
vaccine companies.

The BIO report stacks up other numbers to make the same point: The investment in companies developing vaccines for infectious disease is relatively minor compared with the investment elsewhere. For example, just 16 companies per year, on average, with vaccines against infectious diseases as their lead product were financed between 2013 and 2022. During that same period, an average of 207 oncology companies were financed each year, the BIO report says. Through public share offerings, companies focused on vaccines raised a total of $8.7 billion from 2013 to 2022, and most of the public emerging company funding in the past
10 years(70%) came from 2020 to 2022, during the COVID-19 pandemic. That amount is dwarfed by the $90.7 billion raised for oncology companies.

Thomas points out that Moderna, which along with Pfizer is the main supplier of COVID-19 vaccines, was working on agents for cardiovascular disease and cancer before the pandemic. “Vaccines were No. 3,” he says.

Investment in vaccine-focused companies is lacking partly because of the populations that infectious diseases primarily affect. Although COVID-19 was a reminder that countries with more advanced economies are far from immune to infectious diseases, low-resourced countries are disproportionately affected by the diseases that vaccines might prevent or help lower the number of serious cases.

“Some of these pathogens are only showing up in the developing parts of the world where there isn’t an established access and distribution process,” says Thomas, adding that reimbursement processes may also be lacking. Incidence and prevalence patterns are also a factor, Thomas and Arthur note. Some of the diseases have a low prevalence or the incidence gyrates up and down. “Ebola would be an example,” Arthur says. “It spikes, and then it’s gone and comes back.”

Thomas also points out the irony that a vaccine that is successful in healthcare terms may be sowing the seeds of its commercial failure. An effective vaccine can start a spiral of less disease, followed by decreased need or demand for the vaccine. “In the vaccine space, if you’re really good, you put yourself out of business,” he says.

Investors also look at the cost of developing a vaccine. Even if the success of vaccines in phase 1 trials is slightly better than that for nonvaccines and small molecules, it means that only approximately 10% of vaccine candidates cross the finish line of regulatory approval. What’s more, investors see that the costs are high, partly because the study populations needed to prove efficacy and safety are large.

“The trial sizes are very different from all other development areas,” Thomas says. “In oncology, if you have 500 [participants] in phase 3 study, that’s a big, strong study in oncology. [A vaccine] phase 3 trial, as you saw for COVID-19, may need 30,000 people and, in some cases, you’re paying $30,000 to $50,000 per patient. So the numbers, from a cost standpoint, add to the risk.”

Some success, some fixes

If vaccine development is an uphill battle, that doesn’t mean there haven’t been some victories. The rapid development of the COVID-19 vaccines is an obvious one.

Arthur mentions MenAfriVac, a vaccine against serogroup A meningococcal meningitis that has eliminated cases of bacterial disease caused by the strain from Africa’s “meningitis belt,” a group of two dozen countries in the middle of the continent extending from Senegal to Ethiopia with high meningitis rates. The vaccine was first used in Burkina Faso in 2010. Some commentators say it is one of the biggest and largely unheralded (at least in the U.S.) public health successes in recent memory. The vaccine was sponsored by a partnership of the World Health Organization; PATH, a Seattle-based global health nonprofit; and the Serum Institute of India, a biopharmaceutical company that is often described as thelargest vaccine manufacturer in the world. The Bill & Melinda Gates Foundation provided funding. The MenFivevaccine, also developed by PATH and the Serum Institute of India, would protect against five additional serogroups.

“I think there are some public-private partnership ideas that actually have driven some really good [research and development] of some products,” Arthur says. The funding of those efforts don’t show up in investment tallies in the BIO report, which is focused on venture capital investment.

Thomas and Arthur — and the BIO report — say other important steps need to be taken to spur more investment in vaccines. Chief among them is platform designation. The Consolidated Appropriations Act, 2023, which President Joe Biden signed in December 2022, included a host of provisions concerning the FDA, such as a new program that would allow manufacturers to gain platform designation. If they did, the FDA’s review of drugs developed on the same platform would be expedited. Arthur says an FDA guidance on the platform designation is overdue. She has high hopes that the FDA will follow through.

“If you had an adjuvant, awell-characterized platform, together with a really big body of safety data and a well-characterized manufacturing structure, you could shorten your development times, and that in itself decreases the cost of [research and development],” Arthur says.

The BIO report also calls for reform at the CDC and the Advisory Committee on Immunization Practices (ACIP), the group of outside experts that makes crucial recommendations on how vaccines should be used. Important changes have already been made, Arthur notes. Insurers and others used to wait until ACIP recommendations were published in the CDC’s Morbidity and Mortality Weekly Report,which occurred months after the committee’s vote. Now the recommendations are considered final once the CDC director signs off on them. The BIO report calls for other changes at the CDC and ACIP, including adding expertise on subpopulations, such as older people; increasing knowledge and understanding of the vaccine pipeline and technology; and broadening the evaluation of vaccines to include guidelines on assessment of their health economics and platform technologies.

Arthur says conversations withCDC subject matter experts should occur earlier. But companies should also be conferring with officials with a broader view.

“A passionate expert on a certain pathogen or disease thinks that the disease must be heard,” Arthur says. “They’re excited, they think that disease needs to be prevented. It is the most important thing, right? They’ve pursued it as a lifelong [project], but you can actually have a little bit of an issue when it’s not clear how the deployment of resources might be viewed, which is more of the ACIP process. So how can you have conversations the way you do with the FDA as a drug sponsor? ‘I am thinking about X. What kind of data do you feel would be most important, scientifically, implementation-wise?’ ”

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