One mid-stage success out of two has convinced Hvivo of the merit of pushing into pivotal trials with its universal flu vaccine candidate FLU-v. Whether it will be enough to help the company secure a partner for the next stage of development is another matter.
Hvivo’s executive chairman, Trevor Phillips, believes that the best way forward is to license or sell FLU-v to an experienced vaccine developer – but tells EP Vantage that if a suitable deal does not emerge the company is prepared to go it alone: “We have the option of getting government support to fund a phase III programme for this asset, as it’s one of the most advanced ones out there.”
He adds that Hvivo has already had interest on the back of the latest data, from study 003. And the markets seem confident of a deal emerging, with the company’s stock up 50% this morning. But this was from a low base: Hvivo’s shares had been trading at an all-time low after reporting disappointing results in March from the first phase II study of FLU-v.
With a phase III trial likely to be large – the possibility of a 10,000-subject study was raised on Hvivo’s conference call today – any potential partner would have to be pretty confident of success before signing on the dotted line.
Still, it might be a risk worth taking: an effective universal flu vaccine is likely to become a blockbuster as it would solve the issue of unpredictable efficacy with antibody-based seasonal flu vaccines, which need to be modified each year depending on the strains of the virus expected to be prevalent – a guessing game that does not always pay off.
Other advantages with FLU-v include its synthetic manufacturing process, meaning that it does not require eggs or cell lines, and the fact it is freeze dried, so could be stockpiled in case of a pandemic.
Back in the game?
For FLU-v to take off, however, it must first prevail in phase III, which is far from a given based on evidence available so far. Numis analysts admitted that they had written off the project, which is being developed by Imutex, a joint venture between Hvivo and Seek, after the failure of the previous 004 challenge study in March.
But things are looking up with data, from study 003, presented this morning. The real-world trial, in 176 healthy volunteers, indicated that FLU-v produced an immune response, and also suggested an improvement in flu symptoms – the latter was not significant, but Hvivo noted that the trial was not powered for efficacy on the symptomatic endpoints.
FLU-v is designed to target conserved internal proteins common to all flu viruses to produce a T and B cell-mediated immune response. Study 003 therefore aimed to test these responses by measuring interferon gamma, a marker of T cell activity, as its primary endpoint, and immunoglobulin M and G, markers of B cell activity, as secondary endpoints.
The trial evaluated two treatment regimens: one contained two doses of FLU-v at day zero and 21, and the other comprised one dose of FLU-v plus one dose of the adjuvant montanide ISA 51 at day zero.
With the adjuvanted regimen the trial hit both endpoints. On the primary, 76% of patients in this group had a T cell response at 42 days, versus 9% in the placebo group, which was statistically significant with a p value of less than 0.001.
The non-adjuvanted regimen did not show a significant improvement on T cell response, so this seems unlikely to be part of any phase III plans.
Until a partner is in place, Mr Phillips is reluctant to discuss phase III development in detail, but he does say: “We think you’d be looking to evaluate immunologic endpoints, infection endpoints and symptom endpoints.”
Presumably, a reduction in the incidence and symptoms of flu will be most important from a regulatory perspective. Although the 004 challenge study is currently a black mark here, Mr Phillips claims that this trial could in fact turn out to be positive after further analysis by the NIH.
The trial did not hit its primary endpoint, a composite score combining the occurrence of one flu symptom and changes in viral load, but Mr Phillips blames the miss on it using the “least sensitive assessment” of viral shedding.
Updated data with a more sensitive viral shedding assay should be available in a week or two, he adds.
Mr Phillips envisages FLU-v being given every three to seven years and is adamant that, if approved, it will not merely be stockpiled, but will be a viable alternative to current seasonal vaccines. But, with question marks hanging over the project, Hvivo still has a lot to do to tempt a partner.
|004||Influenza challenge study of FLU-v vs placebo||NCT03180801|
|003||Real-world study in healthy volunteers||NCT02962908|