Obseva’s lead project, nolasiban, improved IVF’s success rate in a phase III trial, but unanswered questions have caused the stock’s volatility this morning. Not the least of these is why a significant benefit was only seen in patients undergoing embryo transfer at day 5 and not day 3.
There is also uncertainty over whether increasing pregnancy rates at 10 weeks – the primary endpoint of the Implant 2 study – equates to a rise in the live birth rate. This is a controversial point with a rival oxytocin antagonist, Ferring’s Tractocile, which is approved in Europe to halt premature labour but is also used in women undergoing IVF.
In any case, Obseva’s chief executive, Ernest Loumaye, acknowledged during a conference call today that the group would have to carry out a confirmatory trial in the US, and might also need to run another study in Europe. The Swiss company hopes to meet regulators mid-2018 and give an update in the second half – any further clinical trials should begin before the end of the year.
If eventually approved, nolasiban, which is given orally, should be a more convenient alternative to Tractocile, which is infused intravenously over four hours. Still, generic versions of Tractocile, which contains the active ingredient atosiban, are now available, and this might make it difficult for nolasiban to gain a foothold in the market.
This could make it particularly tough for Obseva if it decides to go it alone, something that is still an option in the US and Europe, according to Mr Loumaye – in the latter, the company has said that a sales force of 24-40 reps would be enough; as for the US the group will be targeting around 500 fertility clinics. Obseva is seeking development and commercialisation partners for Asia.
Still, it might have a way to go. So far it has only prevailed in the Implant 2 European trial – hence the need for another US study – and this was a qualified success: the 7 percentage point increase in pregnancies at week 10 appeared to have been driven by the subgroup of women undergoing embryo transplantation at day 5.
Mr Loumaye suggested that this was not a problem, pointing out that the IVF field was moving increasingly towards implantation at day 5; according to the chief exec around 60% of clinics in the US now use this schedule.
One reason is that by this time it is easier to assess which embryos will be more viable in the long term. It is also thought that the uterus is more receptive towards embryos on day 5, perhaps as there are fewer uterine contractions – however, some studies have found similar success rates at the day 5 and 3 timepoints.
Oxytocin antagonists like nolasiban also inhibit contractions so could improve the environment further – but Mr Loumaye said they might also work by increasing vascularisation of the uterus and endometrium.
There are still reasons to be cautious about nolasiban – notably, it flunked the phase II Implant trial and Obseva only managed to find a path forward by excluding patients with high progesterone levels.
Developing fertility treatments has been fraught with controversy, as Ovascience found out when conflicting data with its Augment procedure prompted a share price collapse (OvaScience falls in wake of first data but still no baby, April 2, 2015). Part of the problem with the data was the difficulty of linking it with increases in actual births.
Indeed, Mr Loumaye admitted today that what really counted were ongoing pregnancy and live birth rates – and here nolasiban has not yet managed to show an improvement.