The disastrous failure of Versartis’s long-acting growth hormone somavartan yesterday has given an immediate boost to its nearest rival, Ascendis Pharma, which opened up 44% this morning.
The fate of Versartis itself is, of course, far less clear after its own stock crashed 86%, and somavartan is assumed to be dead in the water after not managing even to show non-inferiority to a standard daily growth hormone. The pipeline of long-acting projects – an area that despite several attempts the industry has failed to crack – has thus been thinned down from four to three (see table below).
As the smallest developer Ascendis has seen the biggest stock boost. Its Transcon Growth Hormone is about to complete phase III enrolment, but approval is not expected until 2019; Leerink analysts had earlier opined that Ascendis could move 20% in either direction on the Versartis readout.
Even this has turned out to have been an underestimate. Versartis yesterday said Velocity, somavartan’s pivotal trial in growth hormone-deficient children, had failed to show non-inferiority to Pfizer’s Genotropin in terms of boosting 12-month height velocity.
The non-inferiority bar had been set low, and would have been met had the lower bound of somavartan’s efficacy range come in at 2cm below Genotropin’s or better; yet somavartan failed to show even this in the all-comers population. Non-inferiority was demonstrated in study completers, Versartis said, adding that discontinuations on somavartan were lower than on Genotropin.
But the thinking is that the failure was a case of control performing better than expected, since somavartan’s efficacy came in in the expected range. The project remains in a phase II trial in adults, but starting a pivotal study here is now in serious doubt.
Perhaps Versartis had set such a low bar in the knowledge that a long-acting product would significantly improve convenience for patients and make up for perceived efficacy shortcomings.
At present growth hormone-deficient patients have to inject themselves daily, and the market is split between a handful of products, including Novo’s Norditropin, Merck KGaA’s Saizen and Lilly’s Humatrope in addition to Genotropin. Novo is also pursuing a long-acting project, as are Opko Health and Pfizer.
|Long-acting growth hormones in pivotal development|
|Somapacitan||Novo Nordisk||NCT03075644||Sep 2018|
|Transcon Growth Hormone||Ascendis Pharma||NCT02781727||Nov 2018|
However, the omens are not good, with previous attempts to develop long-acting products by Pfizer, Merck KGaA and Novo falling flat over safety concerns, manufacturing problems and poor efficacy. The only one to be approved, Roche’s Nutropin Depot, was withdrawn after being linked with pain on injection and showing poor efficacy.
Versartis’s somavartan offered the possibility of dosing just twice a month, while the other three current late-stage competitors are once weekly. Ascendis bulls must now compare and contrast the rival study designs, but little can be gleaned from Velocity until Versartis presents the full dataset.
Leerink analysts point out that, while Ascendis’s pivotal trial and Velocity have broadly similar designs, there could be important differences in baseline growth hormone deficiency severity – as was the case in phase II. Another consideration is whether the Velocity failure suggests that efficacy of current therapies has raised the bar for comparative height velocity.
Either way the analysts reckon Transcon Growth Hormone could become the best in class. True, in Versartis a competitor has been eliminated, but the failure points yet again to the difficulty of this space for all concerned.