Exciting and upcoming developments, years in the making.
The drug approval process is infamous for its complexity and the length of time it takes. 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 average six to seven years for a standard drug. In addition to the longer development period, vaccines also have a lower success rate-fewer than 10% of vaccine candidates ever reach the market, compared to about a 12% success rate 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.
One study from the Duke Global Health Institute’s Center for Policy Impact in Global Health forecasts a bleak future for vaccines. Analyzing more than 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.” The study concluded that there is a significant gap in funding.
However, not all the pipeline news is bleak. From improved flu vaccines to the first C. diff (Clostridioides difficile-until recently called Clostridium difficile) vaccines, there are many exciting recent and upcoming developments in 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. While measures have been made to reduce overprescribing, C. diff still directly leads to around 15,000 deaths annually and is still a “major health threat,” according to the CDC.
There are C. diff vaccines in the pipeline, but that pipeline took a hit when Sanofi ended trials of its promising vaccine in late 2017. However, there are still two good candidates in the works.
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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, but 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 it will only continue trials if there is another vaccine approved and it can perform a head-to-head trial. That gamble could pay off though-Valneva says the market potential for prophylactic C. diff products could exceed $1 billion annually.
Every year, according to a 2018 article 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, those numbers are much lower than the CDC desires.
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 multiple announcements on why the vaccine was not effective and what the FDA was doing to increase that effectiveness.
But 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.
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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 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 five to six 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.
Because viruses only grow in living cells, viruses for vaccines must be propagated in cells. For flu vaccines, this is often done in chicken eggs. This process can lead to egg-adapted changes in viruses, which create viruses that are 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.
Another pipeline candidate is Seqirus’ Fluad QIV, an upgraded, quadrivalent 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.
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 10-serotype drug in phase 2 trials that 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.
Current meningococcal vaccine schedules can be confusing for everyone. 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.