Welcome to your weekly digest of approaching regulatory and clinical readouts. Topline data from two phase II trials of Afferent Pharmaceuticals’ antitussive AF-219 are imminent, and the company needs them to be positive if it is to make a success of its planned IPO.
Bavarian Nordic, meanwhile, will soon see three interim analyses of its phase III trial of the prostate cancer therapy Prostvac. If the study is stopped for efficacy Bristol-Myers Squibb could exercise its option to license the project, handing Bavarian $80m.
Afferent Pharmaceuticals raised $55m in a series C round back in July, and has made no secret of its ambition to go public. Participants in the series C, which included the crossover funds Fidelity, Jennison Associates and New Leaf Venture Partners, will be closely watching for the results of phase II trials of AF-219, Afferent’s only clinical candidate, to gauge their chances of making a decent return.
AF-219, a P2X purinoceptor 3 antagonist licensed from Roche, is in two 30-patient phase II studies in chronic refractory cough, one in Europe and one in the US.
According to clinicaltrials.gov, the US study, AF219-010, has a placebo controlled crossover design that will see patients receive AF-219 as a 50mg pill twice daily for 16 days in the active treatment phase. The primary endpoint is reduction in cough frequency as assessed by 24-hour sound recordings.
In the European trial, AF219-015, patients received a single oral dose of AF-219 50mg with the aim of determining whether AF-219 can increase the threshold for coughing as concentrations of inhaled capsaicin are increased to stimulate coughing.
If these studies hit, phase III testing could begin in 2017. The California company is also testing the project in idiopathic pulmonary fibrosis – a six-patient phase II trial is due to read out soon – and phase II trials in osteoarthritis and cystitis/bladder pain syndrome have also been conducted.
More immediately, though, a hit would set Afferent up nicely for a float and a new phase in the company’s development.
Futility and efficacy
Bavarian’s Prostvac, an allogeneic vaccine, looked like it was getting left behind in the fast-paced prostate cancer area until Bristol-Myers Squibb stepped in with a $60m option deal in March (Bristol bets that yesterday’s prostate vaccine could score tomorrow, March 4, 2015).
Bristol’s striking of a formal alliance would be worth an $80m milestone to Bavarian, likely triggered by efficacy data from Prostvac’s 1,298-patient phase III trial, Prospect, which completed recruitment last December. While final readout, after 534 deaths, is not expected until next year the promise of three interim analyses is a key investor focus.
This is because an early halt for efficacy could trigger Bristol’s exercise of the deal early.
Edison analysts believe that the first of these event-driven analyses will most likely assess futility, with efficacy examined in the last two; as such, in the near term there is a risk that Prospect might fail, though this seems unrealistic in light of the phase II data.
That earlier trial had shown median overall survival of 25.1 months for Prostvac versus 16.6 for placebo, with a 44% reduction in risk of death. Prospect is being run under a US special protocol assessment targeting an 18% reduction in risk of death, so it is a safe bet that an early separation of the survival curves suggesting greater benefit than this might lead to an efficacy halt.
What could go wrong? For one thing the phase II survival benefit might have been unrealistically inflated by an imbalance in patients recruited into the two study arms, as argued by Kerrisdale Capital, a fund that is short Bavarian. Another point is the long history of failure of cancer vaccines, though there are important differences between Prostvac and Dendreon’s Provenge, for instance.
Then there is the entry into the prostate cancer paradigm of highly efficacious new treatments like Medivation/Astellas’s Xtandi, Johnson & Johnson’s Zytiga and Bayer’s Xofigo. The introduction of these treatments in placebo patients whose disease progresses has scuppered the studies of Takeda’s ortoronel and Active Biotech’s tasquinimod, for instance.
That said, Bristol’s bet – cautious though it is – endorses Bavarian’s move to embark solo on the Prospect trial. Early success would set Bavarian up for $420m of near-term milestones, though failure would vindicate Kerrisdale’s short position.
|Bavarian Nordic||Prostvac||Prospect||1,200 pre-chemo patients, Prostvac + GM-CSF vs Prostvac vs placebo, median OS primary endpoint||NCT01322490|
|Afferent Pharmaceuticals||AF-219||AF219-010||30 patients, AF-219 vs placebo, cough frequency primary endpoint||NCT02349425|
|Afferent Pharmaceuticals||AF-219||AF219-015||30 patients, AF-219 vs placebo, cough reflex sensitivity primary endpoint||NCT02397460|