1) You’ve been a researcher with The George Institute for Global Health for more than 15 years, can you tell us about your work there, and how you first got involved with George Medicines?
My work at The George Institute is to support the mission to improve the health of millions with better treatments for the world’s biggest health problems, with my focus being on cardiovascular disease prevention. I first got started in helping to establish the evidence around blood pressure drugs and other cardiovascular preventive therapies, such as lipid-lowering agents and aspirin. It was really once that first wave of evidence came out, when it became clear that many more patients should be receiving those treatments globally, that’s when we started this journey with George Medicines. Our goal was to further progress the research from The George Institute by robustly developing therapies that could one day make it to patients.
2) Tell us more about GMRx2’s development journey. When did your involvement with GMRx2 begin?
It all began with a trial that The George Institute conducted with our partners in Sri Lanka, called the TRIUMPH study, investigating the potential of a low-dose triple combination of blood pressure treatments. The results were published in JAMA in 2017 and showed this new paradigm of low-dose combination therapy gave important improvements beyond standard of care. Even though standard of care involves more titration, drugs and doses, the simplicity and the efficacy of this low-dose triple combination was superior. The main issue following that trial was that it was a research-only formulation that was made just for the purposes of that particular trial, and we couldn’t give it to patients long term.
And so that was a big catalyst for George Medicines’ creation – getting a great formulation together and then converting the Institute’s research into a medicine that would allow regulatory approval by authorities worldwide. This led us to GMRx2, our novel, low-dose, triple combination candidate of best-in-class medicines, telmisartan, amlodipine and indapamide for the treatment of hypertension, including initiation of treatment, which we’re incredibly proud to have filed for approval with the US FDA last month.
3) George Medicines recently reported positive results from its two pivotal international Phase III trials of GMRx2, can you tell us more about the data and how it compares to current hypertension treatments?
There were two pivotal trials required to support the FDA approval programme which we presented at the European Society of Cardiology (ESC) Congress in London recently, and we’re very pleased with the results.
Our first, larger trial, in almost 1400 patients, looked at GMRx2 in the low-dose and standard-dose forms against all the possible dual combinations to establish the contribution of each component of the triple therapy. GMRx2 outperformed each of the dual combinations in reducing blood pressure, meeting all of its efficacy endpoints. And there was no increase in withdrawal of treatment due to adverse effects.
The second trial compared GMRx2 in its two ultra-low dose and low-dose forms against placebo, to look at the full effects, benefits and tolerability. Again, the trial met all its efficacy and safety endpoints with good tolerability, and we saw significant improvements in blood pressure control, even at ultra-low doses.
What I find really exciting is that this evidence supports the early use of a low-dose combination, so getting people onto highly effective treatment straight away, or helping those who haven’t got to their target blood pressure on monotherapy or dual therapy. The other interesting point is that we achieved the positive results at lower starting blood pressures than previous trials, which aligns perfectly with recent guidelines pushing for lower blood pressure targets.
4) What impact could GMRx2 have on improving patient adherence and overcoming challenges in hypertension management?
Hypertension is still a massive problem globally, even in places where access to healthcare isn’t the main issue, and we hope GMRx2 will have a significant impact both in high and low income settings. It was developed based on the idea that patients, even those starting treatment, could get the benefits of three drugs without the increase in adverse effects and challenges associated with taking them separately and at standard doses. And it’s one pill, so can help with adherence and patients taking their medicine properly.
Our expectation is that GMRx2 would have adherence advantages that we know come with single-pill combinations, but also, importantly – and there’s an interesting thing about the pharmacology here – even at the very low doses of GMRx2 you retain most of the benefit of a triple therapy, but you miss most of the side effects. This is quite a different approach compared to current combinations.
There’s been a big realisation in recent years about the benefits of lower blood pressure in terms of preventing the leading causes of death, such as heart attacks, stroke, and increasing evidence that it prevents dementia. The existing tools in the toolbox, unfortunately, have pretty low efficacy when used as monotherapy, and so we’ve aimed to develop a product that would be considerably more effective without jeopardising the safety profile, and that it remains affordable globally, and convenient to use.
5) Why does hypertension continue to present such a global challenge?
It’s an important question. We’ve been used to thinking it’s just a small minority of the population who have hypertension, but actually most adults have non-optimal blood pressure, not just in Western societies, but across the globe. So there is a huge need for better prevention. Plus it is generally agreed that those at raised risk should also receive drug treatment, to reliably achieve lower blood pressure levels.
So many people are so far off the optimal blood pressure that it’s a challenging condition to treat. We measure blood pressure in millimetres of mercury and pay most attention to systolic pressure, the maximal pressure when the heart is contracting. Optimal systolic pressure is in the 120s or below and many people start treatment in the 140s to 160s. Most people with high blood pressure aren’t getting it under control, mainly because they’re often just prescribed one medication initially and often stay on that or don’t get their therapy increased much. Monotherapy only reduces systolic pressure by 10 millimetres or so in terms of efficacy. So a concerted effort is needed to better control blood pressure for the many millions of people affected globally. With GMRx2, we might have a way to treat high blood pressure more effectively, right from the start.
6) What are the potential benefits and challenges of implementing this triple single-pill combination on a broader scale in healthcare?
Change comes slowly in medicine, and that’s one of the challenges here. The product was formulated to minimise side effects by using low doses and that’s one of the key potential benefits – you keep most of the benefits, but you don’t increase side effects. But still, some clinicians may add up the number of drugs and think that that’s an automatic indicator of more side effects, so I think that’s a challenge to overcome.
The other challenge is making it available and affordable. But that’s part of our mission at George Medicines, we’re really committed to improving access in many other places around the world, including Africa.
7) How have the trial results presented at the European Society of Cardiology (ESC) Congress been received so far by the hypertension community?
The trial results have been very well received, as evidenced by the editorials and publications in respected medical journals following the event. The true impact will become clearer over time as they are incorporated into guidelines and clinical practice, and ultimately, we see how these findings translate into real-world patient care and outcomes.
8) What does it mean for you personally to see the development programme reach this point, given you are one step closer to delivering GMRx2 to patients?
It’s a very exciting time – a bit like the race to the start line! It’s all very well doing studies for academic papers, but there’s not a practical purpose until there’s a product available for use in large numbers of people globally, and getting to regulatory approval is the start.
There’s still work to be done, but I’m genuinely excited about what this could mean for patients. If we can control blood pressure better, and earlier, we could make a real dent in the number of heart attacks, strokes, and other complications associated with this condition.
It’s been a long journey to get here, but seeing these results makes it all worthwhile. I can’t wait to see what the future holds.