Peregrine’s bavi data: too good to be true?

It would be logical to expect the phone lines to Peregrine Pharmaceuticals to be jammed with calls from companies desperate to do a deal now that the cash-strapped US biotech has reported a stellar survival result in lung cancer with its antibody bavituximab.

Not so fast. Although it is undeniable that on the face of it a doubling of median overall survival to 12.1 months in this setting looks like an unprecedented knockout result, much has yet to be revealed about the robustness of the data. Rather than a licencing pact, it is more likely the US biotech company will take advantage of its share price, up almost 90% over the past five days, to complete a much-needed equity fund raising.

What caused such a stir on Friday was the disclosure of phase II results showing a statistically significant overall survival benefit – a secondary endpoint – in the 1mg/kg bavituximab arm as well as in a post hoc analysis of pooled data from this and the 3mg/kg dose.

The placebo-controlled study, in 121 non-squamous NSCLC patients who had failed one prior chemotherapy regimen, was unblinded in May after it was determined that its primary endpoint, objective response, had been reached. The latest results were presented at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

Shares surge

Peregrine’s stock surged, ending Friday up 47% and giving the company a valuation of $469m – up over fourfold since the start of the year and a far cry from the situation in March, when the shares were threatened with delisting from Nasdaq. The increase was at least partly due to short positions being covered, given how heavily shorted Peregrine had been (Peregrine soars on cancer antibody hopes, August 13, 2012).

The 1mg/kg group had median overall survival of 11.1 months, beating placebo at 5.6 months with statistical significance of p=0.0286. Although the 3mg/kg group also showed a strong numerical increase of 7.5 months over placebo this was not statistically significant; the two groups together achieved median overall survival of 12.1 months with p=0.0154.

Yes, median overall survival was only one of several secondary endpoints hit and the pooled result is less robust still, having been done on a post hoc basis. But what is remarkable is that phase II trials are normally run with the aim simply of informing the design of larger phase III studies, and are typically nowhere near big enough to hit statistical significance.

As such it hardly seems to matter that the primary endpoint was missed across both groups, as was the secondary endpoint of progression-free survival, although there were numerical increases favouring bavituximab in both measures. To have shown a survival benefit – let alone one as numerically large as this – is a hugely unexpected result.

How sound is the result?

Which perhaps is what makes it look like a fluke. In comparison, Roche’s Avastin, which is an approved first-line treatment, increases median overall survival by just two months. Bavituximab had earlier failed a first-line trial in which it was added on top of paclitaxel and carboplatin.

And the fact that half of the centres in the Peregrine study were based in Russia, the former USSR and India – not exactly paragons of clinical rigour – complicates matters further. Although Peregrine has stressed that baseline characteristics were well balanced across the three groups, and that analysing the data by age, gender and ethnicity revealed no variations across the groups, it has not yet revealed precisely how the baseline characteristics or data look if cut by reporting centre.

There might not be a huge amount of error, but given how small the trial was just a couple of patients might make all the difference.

Peregrine says it is now focused on finding a partner to fund a phase III trial. With around 12 months’ cash thanks to a recent $30m loan the company is not in a particularly strong bargaining position, and however impressive the survival benefit is any partner will likely scrutinise the data to its finest detail as well as wanting to see it replicated.

With the shares up another 5% in early trade today the time must surely be ripe for Peregrine to tap the public markets for more cash. Too many unknowns remain to say whether what was until recently a penny stock could be sitting on a future blockbuster.

To contact the writer of this story email Jacob Plieth in London at [email protected]