Versartis got an unexpected boost with positive 18-month results from an open-label extension study of its long-acting recombinant growth hormone VRS-317. The company’s stock surged 20% on the news, but there are still several reasons to remain cautious about its prospects.
One is safety. There were three incidences of “IGF-1 excursions” – insulin-like growth factor-1 levels well above the normal range – which Morgan Stanley analysts think is worth keeping an eye on. There is also the issue of increasing competition from other long-acting growth hormone products in development (see table).
VRS-317, also known as somavaratan, was expected to be the first long-acting growth hormone to be approved in children, but it seems to have lost ground to Ascendis’s once-weekly contender ACP-100 – both are now forecast for launch in 2018.
Versartis was delayed when the FDA put the pivotal Velocity trial of VRS-317 partially on hold in May, but this was lifted in July.
Meanwhile, Novo Nordisk’s NN8640 and Opko Health/Pfizer’s MOD-4023 are both in phase III trials – but in adults with growth hormone deficiency. Versartis is also testing VRS-317 in adults, in the phase II dose-finding Vital trial.
|Selected long-acting growth hormone products in development|
|Novo Nordisk||NN8640/ NNC0195-0092||Phase III (adults)||Once weekly|
|Pfizer/Opko||hGH-CTP||Phase III (adults)||Once weekly|
|Versartis||VRS-317||Phase III (paediatric)||Twice monthly|
|Ascendis||ACP-001||Phase II (paediatric)||Once weekly|
Versartis does have the advantage of a twice-monthly dosing schedule, while the other candidates are given once weekly. All should have an edge over currently approved treatments, which are given via daily subcutaneous injection.
The new data could help set VRS-317 apart in a market "ripe for disruption by longer-acting agents", according to Credit Suisse analysts. They estimate the sector is worth around $3bn currently and will rise to $4bn in 10 years.
The extension study suggested that VRS-317 could maintain a relatively stable height velocity at 18 months. Patients were given either 5mg/kg monthly or 2.5mg/kg twice monthly for the first year, then switched to a higher dose of 3.5mg/kg twice monthly.
This increase in dose was designed to combat a slowdown in growth that is seen in the second year of treatment with current daily drugs.
And it seemed to work: the study found a mean height velocity of 7.9cm and 8.5cm with the 5mg/kg monthly and 2.5mg twice-monthly doses respectively at 12 months – at 18 months this was similar at 8.1cm and 8.3cm respectively.
Full 18-month results from the extension study will be presented at a late-breaking poster session at the European Society for Paediatric Endocrinology meeting in Barcelona in early October. The trial is assessing patients for up to four years in total.
Versartis is testing the 3.5mg/kg twice-monthly dose in the pivotal Velocity study, which also includes a comparator arm in which patients will receive daily growth hormone therapy.
In spite of VRS-317's potential, analysts seem nervous that it might underperform versus once-weekly agents, or that safety concerns will continue. This is reflected in falling forecasts for the project; as recently as May sales of around $900m were predicted by 2020, but consensus is now just $170m.
Versartis might have to wait until it reports interim results from Velocity – due in the second half of next year – before its stock starts picking up speed again.
|Versartis Long-Term Extension Study of VRS-317||NCT02068521|