The data released by Dyax on hereditary angioedema therapy DX-2930 are undoubtedly highly encouraging. They are also undoubtedly very early, having been generated in only 15 patients who received two doses of what could eventually be used as a chronic therapy.
These cautionary facts were not sufficient to contain the exuberance of investors, however, who added $1.1bn to the company’s value in early trade today, growing its market cap by 50%. If Dyax can replicate these results in larger studies, as it confidently predicted, then this is probably justified. But it is a bold position to take, particularly when considering that the FDA has yet to endorse the company’s plan to push straight into phase III and seek approval on a single trial.
Dyax management did little to supress hopes that this is exactly what might now unfold and, to be fair, it also announced yesterday that the FDA had granted the product, an antibody inhibitor of plasma kallikrein, fast track designation.
“We are certainly of the mind that one adequately sized study with this kind of efficacy – and as long as the safety profile continues to be compelling - should be adequate,” said Burt Adelman, chief medical officer; he also raised the prospect of winning breakthrough therapy designation from the FDA.
This would represent a serious fast forward for the project; as recently as February the company indicated that a phase II study would be the next step. It was also widely assumed two phase III studies would be required because there is already a product on the market in the US to prevent the dangerous attacks of tissue swelling that characterises this rare disease – Shire’s Cinryze.
The data generated from a phase Ib trial has changed all this, however, according to Dyax and the investors that piled into the stock this morning at least.
In total 37 patients were recruited across four dosage groups or a control arm, each of whom received two doses of DX-2930 or placebo, 14 days apart. The frequency of attacks over day eight to day 50 after administration was measured and compared to baseline.
The primary efficacy analysis – which was pre-specified - was conducted on subjects who met the criteria of having at least two attacks in the three months prior to the study. This yielded 11 of 13 placebo patients for analysis, and 15 of 16 subjects treated with the two higher dose groups; results from the lower dose groups were not disclosed and presumably are not going to be investigated further.
The 15 DC-2930 patients registered a 91% reduction in attacks per week versus placebo (p=0.0012); the two separate cohorts also hit significance with a 100% and 88% reduction in attacks, at 300mg and 400mg respectively.
The placebo group experienced 24 attacks over the evaluation period, while none were recorded in the 300mg group and three in the 400mg group.
All of which looks encouraging, particularly when considering the relative effectiveness of rivals, the caveats of cross-comparison notwithstanding. Cinryze, an enzyme replacement therapy which needs to be infused twice a week, reduces attacks by about 50%, while Biocryst’s BCX4161 managed to achieve a 35% reduction in a phase IIa trial last year; the product’s oral delivery is its unique selling proposition (BioCryst pushes positive HAE news and taps market once again, May 29, 2014).
Room to disappoint
It seems highly unlikely that this level of effectiveness will be maintained across a larger study. But given that the drug is a subcutaneous injection that might only need administering every two weeks – a schedule that is unlikely to put off patients suffering a debilitating chronic disease – there is room for its efficacy to wane somewhat and still look competitive.
Not that Dyax was willing to entertain such notions. “We think we should continue to get results as we see here,” Mr Adelman predicted.
Much now depends on regulators adopting a similarly optimistic stance and concluding that the risks and benefits of the project – as far as they can be assessed in such a data set – warrant pushing straight into a single pivotal study.
Investors are clearly already willing to buy in to a best case scenario. But it leaves the company with little room to disappoint.