What You Need to Know About the Vaccine Pipeline

The drug approval process is infamous for its complexity and the length of time to develop. But as complicated as standard drugs are to develop, biologics-such as vaccines-are more complicated.

On average, vaccines take about 10 to 15 years to develop, compared to the

for a standard drug. In addition to the longer development period, vaccines also have a lower success rate-

ever reach the market, compared to about a

for drug candidates overall.

That long lead time and high failure rate means that a large number of needed vaccines are still missing from healthcare’s armamentarium.

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One study from the Duke Global Health Institute’s Center for Policy Impact in Global Health forecasts a bleak future for vaccines. Analyzing over 500 vaccine candidates for 35 neglected diseases in the pipeline, the study found the chances of efficacious vaccines gaining approval over the next five years is “unlikely.” This study concluded that there is a significant gap in funding.

However, not all of the pipeline news is as bleak. From improved flu vaccines to the first

C. diff (Clostridioides difficile (what was until recently called Clostridium difficile) vaccines, there are many exciting recent and upcoming developments in vaccines.

Clostridioides difficile vaccines

C. diff infects close to half a million Americans every year, according to the CDC. A large reason for the spread of C. diff is inappropriate antibiotic prescribing. According to the CDC, about 30% of antibiotic prescriptions are unnecessary-and while measures have been made to reduce overprescribing, C. diff still directly leads to around 15,000 deaths annually. The CDC concludes that C. diff is still a “major health threat.”

Beyond reducing overuse, part of the fight against those infections are vaccines in the pipeline. The C. diff vaccine pipeline took a hit when Sanofi ended trials of its promising C. diff vaccine in late 2017. However, there are still two good candidates in the pipeline.

The current frontrunner is Pfizer’s PF-06425090. After favorable phase 2 trials, Pfizer is hopeful that phase 3 trials, set to conclude late next year, will allow the vaccine to be the first C. diff drug to grant long-term protection.

VLA84, from Valneva, is another candidate that ran into money problems. While the company says its vaccine is ready for phase 3 trials, it has put those trials on hold due to lack of a partner to help shoulder the cost of trials. Valneva says that they will only continue trials if there is another vaccine approved and it can perform a head-to-head trial against it. That gamble could pay off though-Valneva says the market potential for prophylactic C. diff products could exceed $1 billion annually.

Influenza vaccines

Every year, according to an article published last year in Vaccine, influenza results in $3.2 billion in direct costs, along with $8 billion in indirect costs. The last flu season resulted in 959,000 hospitalizations and 79,400 deaths, according to the CDC.

Despite this, flu vaccination rates remain low-the CDC estimates that only 37.1% of eligible adults received a flu vaccine over the 2017-2018 flu season. While initial reports those numbers may be slightly higher over this most recent flu season (full data won’t be available until September this year), those numbers are much lower than the CDC would like.

While the general population gives a wide variety of reasons for not getting a vaccine-including unfounded fears of getting flu from the vaccine or not having access-many people (particularly younger people) cite the fact that the flu vaccine doesn’t work. This notion isn’t without weight: The 2017-2018 flu vaccines had such a low efficacy rate (36%) that former FDA Commissioner Scott Gottlieb, MD, made multipleannouncements on why the vaccine was not effective and what the FDA was doing to increase that effectiveness.

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Recently-approved and as-yet-unapproved products could make that dream of a more effective vaccine a reality.

Flucelvax, from Seqirus, is the only cell culture-based flu vaccine available in the United States, first approved in 2016. This formulation, based on preliminary studies, seems to perform much more favorably than traditional egg-based flu vaccines.

What’s most exciting about cell culture-based vaccines though, according to the FDA, is their ability to be quickly manufactured-making them an ideal candidate for dealing with possible pandemics.

Another exciting prospect in the pipeline also relies on something other than an egg base. Medicago’s VLP quadrivalent plant-based flu vaccine, currently in phase 3 efficacy trials in seven countries including the United States, could present another option for faster-produced, more effective vaccines.

Medicago says that it’s plant-based process requires only five to six weeks to produce a clinical-grade vaccine, compared to the 5 to 6 months it generally takes for egg-based vaccines. This speed, the company says, could allow for it to more easily keep up with the constantly-mutating flu virus.

This is due to the fact that egg-based vaccines are susceptible to changes. Because viruses only grow in living cells,

. For flu vaccines, this is often done in chicken eggs. This process can lead to egg-adapted changes in viruses, which create viruses different than those found in the wild. While some research suggests that these egg-adapted changes are not always responsible for poor-performing flu vaccines, it may be a factor that if eliminated could result in much more effective vaccines.

Another pipeline candidate is Seqirus’ Fluad QIV, an upgraded, quadravalent formulation of its already-approved trivalent Fluad. If approved, Fluad QIV would be the first adjuvanted quadrivalent flu vaccine. According to Datamonitor Healthcare, it performs better than other traditional inactivated flu vaccines, meaning that in its expected launch for the 2020-2021 flu season it could capture a large part of the elderly population.

While perhaps more tenuous, new so-called universal flu vaccines are designed to cover all strains for several seasons. They could help increase protection over multiple years and avoid problems with shifting virus strains-if they receive approval and demonstrate those claims. Datamonitor Healthcare says that if approved, these vaccines could hold great promise, as they could boost confidence in vaccination and increase coverage rates.

One of the best candidates, BiondVax’s M-001 is currently only in phase 2 in the United States. However, it has been a part of multiple successful Phase 2 studies in Europe and Israel, and is currently in Phase 3 in Europe. FLU-v from hVIVO is another phase 2 universal vaccine candidate, and it too is set to begin phase 3 trials in Europe.

One potential problem for universal vaccines, according to Datamonitor Healthcare, is that payers are looking for low-cost vaccines-indicating that these could be priced higher than traditional vaccines.

Pneumococcal disease vaccines

According to the CDC, around 900,000 Americans get pneumococcal pneumonia (the most common form of pneumococcal disease in adults) every year-resulting in over 400,000 hospitalizations. While vaccines exist, the CDC says that about 80% of adults with conditions that put them at increased risk and 40% of adult aged 65 or older are unvaccinated.

Currently, the best-selling vaccine is Pfizer’s Prevnar 13, with about $3.5 billion in U.S. sales forecasted for 2019. The pneumococcal vaccine is the 2010 update to the previously-approved Prevnar 7. First approved in 2000, Prevnar 7 was the first pneumococcal conjugate vaccine. The update added an additional five serotypes to the original, due to the possibility of shifting strains of the disease (known as serotype drift). The CDC recommended in 2014 that all adults over the age of 65 receive Prevnar 13, leading to its massive spike in sales.

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However, other pneumococcal vaccines with additional serotypes could threaten Pfizer’s market dominance.

Merck currently has a 15-serotype vaccine-V114-in phase 3 trials. According to Datamonitor Healthcare, it could replace Prevnar 13 on its expected approval in 2022-if it proves superior to Pfizer’s drug and if serotype drift occurs. GlaxoSmithKline also has a drug in phase 2 trials that, while only a 10-serotype version, is formulated in such a way that it could provide more coverage than Prevnar 13.

One of the biggest threats to Prevnar 13 could be an upgrade to Prevnar-Pfizer is currently working on a 20-serotype vaccine. That vaccine just began its Phase 3 trials earlier this year, so it likely won’t see a release for years.

Meningococcal vaccines

Current meningococcal vaccine schedules can be confusing for patients and physicians alike. All preteens and teens should receive the meningococcal conjugate vaccine, with a booster given at 16, while only some are recommended the serogroup B meningococcal vaccine. That schedule can be affected by a host of other risk factors, potentially adding to the confusion.

GSK’s MenABCW-135Y is trying to clear up that confusion. According to Datamonitor Healthcare, it could achieve this due to its broad serotype coverage-it would be the first vaccine cover serotypes A, B, C, W, and Y, which could allow it to cover a wide range of patient populations. It would then replace GSK’s current Bexsero and Menveo vaccines. This would have the added benefit of reducing the number of physician visits required for vaccination. If approved, it is expected on the market in late 2021.

Another possible ripple in the meningococcal market is Sanofi’s Men Quad TT, a likely replacement to the well-established Menactra. According to Datamonitor Healthcare, it could then charge a premium price if it shows superior immunogenicity to Menactra and Menveo.

However, that premium price may be short lived. While its expected launch date is a full year ahead of MenABCW-135Y (Q1 2020), GSK’s vaccine is likely to overtake it. This would give the vaccine a short window of use.

Longshot vaccines

While early and preclinical trials are generally poor indicators of what will actually come to market, they still provide an interesting look at what might be possible. These are some of the interesting vaccines in very early stages.

Heroin vaccine

Severalcompanies are currently developing a vaccine for heroin that would prevent users from getting high and addicted to the drug. Still in very early stages (human clinical trials have yet to begin, though researchers say they are close), the vaccine could be a much-needed solution to a serious problem-heroin led to 15,482 deaths in 2017, in part driven by the ongoing opioid epidemic.

HIV vaccine

An HIV vaccine has remained elusive for pharmaceutical manufacturers. Currently, the best chance of success is with the study HVTN 702, a South African phase 3 trial set to complete in 2021. That trial is using a modified version of a vaccine first tested in Thailand-that study delivered results in 2009 that showed that it prevented the virus, but the results were modest. The South African study is being cofunded by the National Institutes of Health.

Respiratory Syncytial Virus infection

RSV hospitalizes over 57,000 children each year, along with 177,000 older adults. About 14,000 of those older adults die from the infection each year, according to the CDC. No vaccine exists, the current treatment is palivizumab, which can provide some protection-but requires a monthly shot and isn’t always effective.

While Novavax’s ResVax seemed promising, it recently announced that it failed its primary objective of prevention. According to Datamonitor Healthcare, Novavax has sent its drug back to Phase 2 trials with a different formulation so it could launch for the 2021-2022 season. Two other drugs, Johnson & Johnson’s Ad26.RSV.preF and Bavarian Nordic’s MVA-BN RSV could both launch in the coming years for use in the elderly population.

Nicholas Hamm is an editor with Managed Healthcare Executive