In a blow to hopes for better protection from seasonal flu, last week’s phase III failure of BiondVax’s universal flu vaccine follows the phase II flop of Vaccitech’s flu vaccine in January.
Last week proved a major setback for the Israeli biotech BiondVax. The company’s vaccine — designed to protect against multiple strains of flu — failed in phase III. This was BiondVax’s only clinical candidate and investors reacted poorly, sending the stock into free fall.
Back in June, BiondVax reported that the vaccine had shown promise against flu by activating the immune T cells of healthy volunteers in a phase II trial. However, the vaccine was unable to protect against flu better than placebo in phase III.
“We were very disappointed with the results. We were optimistic because our previous trials had shown that this is an active vaccine,” said Joshua Phillipson, Director of Business Development and Investor Relations at BiondVax.
Going forward, the company plans to investigate what went wrong, and will also consider licensing deals of its vaccine-related expertise, intellectual property, and facilities.
“The candidate itself, we don’t believe is dead. Maybe there’s something we can do to revise it,” said Phillipson. “We have a state-of-the-art vaccine manufacturing facility. Particularly these days, vaccine manufacturing facilities are in demand.”
So why did the vaccine fail in phase III? The company can only speculate at the moment. For example, the vaccine turned out to be just as safe as the placebo in the phase III trial, when you’d normally expect occasional adverse events such as fever. This could indicate the dose was lower than it should have been to see an effect.
BiondVax isn’t the only company to have trouble with a universal flu vaccine this year. A candidate developed by Oxford-based Vaccitech failed in two phase II trials in January this year, leading the biotech company to quietly abandon the program. Vaccitech is now focusing on developing cancer vaccines as well as collaborating with AstraZeneca and the University of Oxford in the development of their phase III-stage Covid-19 vaccine.
Universal flu vaccines are seen by many as a holy grail of flu vaccines. Current seasonal flu vaccines need to be manufactured against the specific strains of influenza that are predicted to circulate that year. The manufacture — most of which is carried out in chicken eggs — can take months, and the vaccines could prove ineffective if the predictions are off.
“Providing a vaccine that is not dependent on the WHO season flu predictions would be of significant benefit,” said Alexandre Le Vert, CEO and co-founder of the French company Osivax. “As such, we believe that a universal flu vaccine is needed to address both seasonal and pandemic influenza.”
There are several contenders globally for the first universal flu vaccine. Examples include Nanoflu, which is being developed in phase III by the US company NovaVax, and a candidate developed by Osivax in phase II. Osivax raised a hefty €32M in July to fund the development of its flu vaccine in addition to one for coronavirus diseases including Covid-19 and the common cold.
The two failures this year demonstrate how difficult it is to strive for a universal flu vaccine. “A universal flu vaccine is one of the most challenging vaccine development efforts,” tweeted Roy van Heesbeen, Process Lead of Clinical Development at Janssen. “Many different approaches are currently being tested but the risk of failure is very high.”
Nonetheless, the other contenders seem confident that their vaccines will work where others have failed. Le Vert believes that the success of a universal flu vaccine hinges on the type of immune T cells that are activated by the vaccine; particularly T helper cells — which play key support roles — and cytotoxic T cells, which destroy infected cells.
“Based on publicly available data and the figure shared in BiondVax’s corporate presentation for [its phase II trial], it seems that this observation was confirmed for [T helper cells] but not for [cytotoxic T cells]. This could explain the lack of efficacy observed in their phase III trial.”
The results of a phase II trial of Osivax’s vaccine are expected in early 2021. The firm aims to confirm whether its vaccine is able to activate cytotoxic T cells, which could let it succeed where others have failed.
BiondVax’s mishap this week is poignant given that the winter flu season is coming. There are concerns that circulating Covid-19 and seasonal influenza viruses will place huge pressure on healthcare systems. To combat this eventuality, the CSL Behring-owned manufacturer Seqirus recently announced it’s shipping a record number of flu vaccines to the EU and Australia.
“The potential for Covid-19 to persist or resurge during the upcoming influenza season is generating significant demand for influenza vaccines,” stated Enric Canelles, Seqirus VP Commercial Operations, EMEA. “It is important to protect those most at risk from influenza because they are also the most vulnerable to Covid-19.”
Furthermore, the experience of BiondVax and Vaccitech could also give important lessons to companies developing vaccines against Covid-19, the most advanced of which are currently in phase III.
“We may learn next month whether the two Covid-19 vaccines furthest along in their phase III trials, from Pfizer and Moderna, actually work,” tweeted Helen Branswell, a health reporter at Stat News.
“There’s a lot of hope that multiple Covid vaccines will work. But vaccine work is tricky. This flu vax news from last week is a timely reminder.”
Image from E. Resko