When it comes to flu vaccines, a universal immunotherapeutic is the holy grail. Abi Millar finds out how UK company SEEK aims to get there first with its FLU-v vaccine, due to enter phase IIb this year.
The past winter was one of the worst in recent memory for flu, with mortality rates in the UK soaring to their highest level in 15 years. While the cold snap was believed to play a role, the primary culprit was pegged as an ineffective flu vaccine, which had been administered to millions of people ahead of flu season.
According to Public Health England, the main strain of flu – A(H3N2) – had mutated since the jab was developed. This meant that in lab tests, the vaccine protected against just 3% of cases, rendering it almost futile.
The situation in the US was little better, with the Centers for Disease Control and Prevention (CDC) recording a severe flu season for elderly people. Out of the H3N2 viruses they analysed, around half were drift variants – antigenically or genetically different from the vaccine virus.
Ordinarily, the vaccine is well targeted at the flu strain in circulation, but there are no guarantees in place. Because there are so many different variants of flu, it is necessary to develop new vaccines each year and mount a new line of attack. Unfortunately, the relevant strain must be predicted many months in advance, allowing ample time for the unforeseen to occur.
“The World Health Organization makes its best guess as to what the strain is going to be for the year, and every now and again they get that wrong,” says Gregory Stoloff, CEO of UK pharmaceutical group SEEK. “That’s what happened in the UK and US this year – they predicted a couple of the strains incorrectly so the vaccine was not effective as it normally is. If the manufacturing process were quicker you could wait until the actual strains were known and then make the vaccine, but because it takes six months you have to guess.”
A universal solution
This system is particularly troublesome in the case of a pandemic. In these instances, the genetic drift is dramatic, and the seasonal jab is unlikely to provide much help. As well as taking a long time to produce, the vaccine can only be manufactured in limited quantities. With some 13 billion doses required to forestall a pandemic – and maximum annual production standing at around 1.4 billion – it simply isn’t possible to produce as many doses as you’d need for blanket protection.
The race is therefore on to develop a universal vaccine – a jab that could be administered once across the population, and would defend against every strain of flu no matter how much the virus mutated. It has been estimated that, over the course of a person’s lifetime, a universal therapy of this kind could save the NHS and the UK economy around £27,000 per capita, due to fewer sickness absences and less strain on the healthcare system.
As well as these cost savings, the broader repercussions could be dramatic. A universal vaccine could eradicate flu altogether, just as earlier vaccines did for smallpox. It could solve a problem that affects between 5 and 15% of the world’s population every year, resulting in around a million hospitalisations and 250,000-500,000 fatalities. This is not to mention doing away with the ever-present threat of a pandemic.
While this situation sounds like a pipe dream, it could become reality sooner than we might anticipate. SEEK is in the process of developing a universal immunotherapeutic for flu, which targets the non-mutating regions of the virus. Having shown promise in early clinical trials, the vaccine is set to enter phase IIb trials this autumn.
“Most vaccines to date try to target the outer proteins of the virus, but the outer proteins in flu change regularly, so this hasn’t led to a successful result,” says Stoloff. “We’ve gone for a totally new approach, which is to look at the internal proteins. In there you find there are a lot more conserved regions that don’t change, and we’ve manufactured small proteins that can train the immune system to recognise those internal conserved regions. If you teach the immune system to recognise them it doesn’t matter what flu you get, your immune system will always be able to attack that strain.”
While many of SEEK’s competitors have been confining their endeavours to the outer proteins, Stoloff believes they are unlikely to be successful. Even though there are conserved regions in this part of the virus, nearby parts can change their shape and block the drug from entering.
“That’s what’s happened with Tamiflu and Relenza, the two antivirals that are currently used to try to reduce the severity of flu,” he explains. “You hear the phrase that certain flus are resistant to those medicines, and that’s what that means – those medicines target those conserved regions on the outside but they can’t always work because the proteins that change block access to that conserved region.”
SEEK’s universal vaccine, FLU-v, should be able to override these problems. Because it targets many of the conserved regions – not just one – it is at negligible risk of losing efficacy in response to genetic drift. There is only a minute probability that all the regions in question could change at the same time.
Fast track hopes
To date, the vaccine has not shown any side effects. A phase I study found it to be safe and tolerable, and a phase IIa study found it to be effective in protecting people from flu and reducing its severity. Should phase IIb trials prove successful, Stoloff expects the drug will be available for fast track approval status.
“We believe we will be able to get to market very quickly under some fast track procedures in America or Europe, and we could potentially have something in the market within 18 months to two years,” he says. “If it comes to market it will have blockbuster potential, because it would be a low-cost product that protects everybody against every strain, in as many doses as you need.”
Of course, it is impossible to say at this stage whether the final phase will work out or whether SEEK’s product will reach the market first. The company is currently in discussions with the regulator, with a view to determining what kind of evidence base they will need before they fast-track the drug. Still, whatever the outcome the possibilities should not be underestimated. When a universal flu vaccine hits the market, cases will drop dramatically and the annual blight may soon become a thing of the past.
“It’s got the potential to eradicate flu in the long-term if you give it to everyone,” says Stoloff. “If you vaccinate all the humans and the key at-risk animals with this product then the reservoir should eventually disappear and flu won’t be around anymore.”
This article appears in the May 2015 edition of Pharma Technology Focus