Solvonis Therapeutics PLC (LSE:SVNS, FRA:J4I) earlier this week shared positive preclinical data for its lead compound, SVN-15, positioning the molecule as a potential first-in-class treatment for depression targeting both serotonin and dopamine systems.
Speaking to Proactive, chief scientific officer Professor David Nutt said SVN-15 matched fluoxetine (Prozac) in head-to-head testing using a validated rodent model of depression.
He noted this was the company’s first study in a model with established predictive value for human response, and also commented on the likely commercial strategy.
Proactive: David, very good to speak with you and congratulations on your latest news. The announcement states that SVN-15 performs similarly to fluoxetine, or Prozac as it’s better known. Can you explain a bit about how strong that result is in practical terms, and what it realistically tells us about the chances of success in human trials?
Professor David Nutt: Well, we're very pleased because this is the first study we have done in a validated model of depression – obviously in rodents. We’re putting it head-to-head with one of the most established and effective antidepressants of the SSRI class, and it performed as well, with the same dose range.
So that is exciting because when you have a new kind of molecule, which SVN-15 is, you're never sure whether the extra bits you've put into the molecule will be good or bad. We assume they're going to be good, but of course you can't predict.
So it turns out that that's certainly not bad. What we need to do now is to see whether we can demonstrate in other models that the pro-dopamine effect actually gives value, in a way which will then translate into extra efficacy in humans.
Proactive: What clear benefits do you expect SVN-15 to deliver that current antidepressants don’t? Especially for patients who don't respond well to SSRIs, and how will you prove that clinically?
Professor Nutt: This molecule is a very unusual one. Companies have been searching for this elusive serotonin-dopamine re-uptake blocker for a very long time, and they have not succeeded.
The reason they’ve been searching is that the dopamine system plays an important role in certain features of depression – particularly fatigue, loss of energy, and the loss of what we call hedonic tone – people don't enjoy things. Where SSRIs like Prozac can stop you feeling depressed, they don't give you the buzz, they don't put the zing back into life.
And we've been arguing for 30 years that a bit of dopamine would do that. And this molecule will give you a bit of dopamine.
Now we have to test it in humans, and it’ll go into studies of depression, particularly in patients who have problems with energy, can’t get up in the morning, don’t have drive, can’t focus for attention, and who just don’t have interest in life.
Proactive: In terms of the targets for SVN-15, are the most likely candidates newly diagnosed patients, or those who haven’t responded well to existing antidepressants? And secondly, how would that choice impact the commercial opportunity?
Professor Nutt: Well, the way new antidepressants tend to be brought in – particularly if they have a new mode of action – is generally to use them in people who haven’t done so well on the old ones. So that would be the most sensible way forward.
That’s still a huge unmet need. We know that about 50% of people treated with SSRIs like Prozac don’t make a full recovery, or are left with residual symptoms, which we think are due to the dopamine system not working very well. So I think that would be the sensible place to target.
But it’s quite possible that this dual-action drug will have a broader effect, even in people who haven’t had prior exposure to antidepressants. So I think in the end, it’s going to be a commercial decision. If we get enough investors, we might well go straight for all depressives.
Proactive: And David, how does the once-daily oral at-home profile change the risk-reward compared with neuro-clinical-based depression treatments? And how does that affect scale, cost and payer acceptance?
Professor Nutt: Well, we’ve spent the last 50 years using drugs which people take at home once a day with good effect. So if we get better effects than previous daily antidepressants, then we will actually be in a really strong position.
Up till now, we’ve been developing these new fast-acting, short treatment-dose approaches with things like ketamine and psychedelics – but they’re out of necessity, because current antidepressants don’t work as well as we hoped.
This dual-acting drug could shift the dial. So we might end up with better outcomes, and perhaps not need to dose as frequently as with these up-and-coming, rather novel treatments.
Proactive: David, congratulations again on this latest milestone. I hope you'll keep us updated with the progress.
