Bristol bets that yesterday’s prostate vaccine could score tomorrow

Just when it looked like Bavarian Nordic had entered the graveyard shift, with no significant news until the 2016/17 readout of Prospect, its pivotal trial of Prostvac, the group scores Bristol-Myers Squibb as a potential partner.

The possibility of signing up one of big pharma’s most important immuno-oncology players is not to be scoffed at, even though the deal’s terms show Bristol to be proceeding very cautiously. Still, the fast-changing field of prostate cancer treatment could have serious implications for the relevance and integrity of Prostvac’s data.

It is perhaps because of this last point that Bristol is showing restraint. In terms of risk-taking the obvious contrast is the deal Bristol did last week with Flexus Biosciences, handing across $800m up front for an immuno-oncology asset that had not yet even entered the clinic.

Its tie-up with Bavarian comprises $60m up front in return for an option over a full licensing deal, which would cost it a further $80m to exercise. Over $250m could become due if Prospect’s median overall survival benefit exceeds that seen in phase II, followed by $605m of milestones, and a double-digit royalty.

The important thing for Bavarian is that the Bristol deal effectively resurrects a project that many industry watchers no longer took seriously, given the charge of highly potent small molecules like Medivation’s Xtandi and Johnson & Johnson’s Zytiga. And the precedent set by Dendreon’s Provenge was not a happy one.

Bavarian’s chief executive, Paul Chaplin, told EP Vantage that the group wanted a global pioneer in the immuno-oncology space that could launch the product, and this is what it got in Bristol. He also pointed out that this was a three-part alliance, the option being separate from a supply contract and combination clinical trial collaboration.

Indeed, it is combo use that now holds the most promise for Prostvac. “We believe Prostvac will be approved as monotherapy but will be used in combination,” said Mr Chaplin.

Just last week results from an NCI-sponsored phase I trial combining Prostvac with Bristol’s Yervoy showed median OS of 37.2 months for one of the doses – a 19-month benefit over historical data – with 20% of patients still alive after 80 months. It might well have been this that focused minds at Bristol.

Thus things are very different now than they were four years ago, when Prostvac, a PSA-directed cancer vaccine, was one of several highly promising prostate cancer projects vying for attention, having generated median OS of 25.1 months versus 16.6 for placebo in phase II. But the group failed to find a partner, and its decision to raise $115m to fund phase III caused a share price collapse.

Back then Bavarian wanted someone to fund the trial, but now the cost has been sunk. “We’ve looked at licensing differently,” said Mr Chaplin, who became chief executive just last year – perhaps bringing with him a new mindset in deal-making.

Changing landscape

Still, the rise of Xtandi and Zytiga poses one obvious problem: that patients in all three arms of Prospect might go on to be treated with these novel agents, masking the benefit generated by Prostvac.

Mr Chaplin accepted that this was a risk, but noted that Prospect was a global study while the novel agents were only available in certain countries. He also suggested a synergistic effect in a possible combo setting: Prostvac works via a T-cell response, and data have shown an increase in T-cells following anti-androgen therapy like Xtandi or Zytiga.

For now the combo focus is with Bristol’s immuno-oncology assets, for which a clear rationale exists too: a checkpoint inhibitor takes the brake off the immune system, before Prostvac induces T cell-mediated tumour destruction. The partners plan to begin their first combo trial this year, with a separate investigator-sponsored Yervoy/Prostvac phase II study also planned.

And those worried about similarities between Prostvac and Dendreon’s Provenge should probably rest easy. Unlike the autologous Provenge Prostvac is off the shelf and has a different target; Dendreon was sunk by non-clinical problems, mispricing its product and accumulating an insurmountable mountain of debt.

Mr Chaplin said Bristol could exercise its option “when sufficient data exist to allow filing a BLA”. This might be before Prospect yields full results in 2016/17 since three event-driven interim analyses are also planned, though what will trigger these has never been disclosed.

Analysts at Jefferies wrote today that they still applied a cautious 40% chance of success to Prostvac’s peak sales expectations of $1.3bn, but noted that Bristol was a leader in the rapidly evolving immuno-oncology field. Prostvac has been endorsed at last, and that is something Bavarian could not boast of yesterday.

All eyes on the pivotal readout
Study Design Trial ID
Prospect 1,200 pre-chemo pts, Prostvac + GM-CSF vs Prostvac vs placebo, median OS primary endpoint. NCT01322490

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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