An update on the PAH drug sotatercept

Posted on December 4th 2023

The PAH therapy sotatercept is the first drug to target the root cause of the disease, and trials have produced promising results. But as 2023 draws to a close, are we any closer to it being made available for patients?

We spoke to two specialists from Royal Papworth Hospital for the update in the video below…

A transcript of the chat we had with Dr Mark Toshner, PH Specialist at Royal Papworth Hospital and Associate Professor at the University of Cambridge:

Thanks for chatting to us about this, Mark. First of all, can you remind us what makes this drug different?

Sotatercept doesn’t work like the other drugs that are licensed for pulmonary hypertension – known as vasodilators – which all work by opening up the blood vessels.

Sotatercept arose from some of the work done in genetic forms of the disease, and in particular in a pathway known as the bone morphogenetic protein type 2 receptor (or ‘BMPR2’ pathway).

Essentially, the drug works by changing the expression of proteins that we know underly the familial [genetic] forms of the disease.

So, rather than just opening up vessels, it works more directly on the underlying ‘problem proteins’ that are causing the disease in the first place.

Sotatercept is also different because it’s taken in the form of nearly monthly injections.

What excites you about this treatment?

This drug is a really big step forward because although the last 20-30 years has seen a lot of changes in the treatment options that we have available for pulmonary hypertension, all those drugs work in the same sort of way, so the benefits have been incremental.

This appears to be a different mechanism, and the results [of the trials] are as good as everything we’ve seen in the last 20-30 years.

Since I last spoke to you at the PHA UK a year ago, the results of the full big trials of sotatercept have been released and we’ve been able to comb over them. The good news is that the drug seems to be having a very significant effect in a very wide group of patients with pulmonary arterial hypertension.

The majority of patients who were in the clinical trials were already on a significant therapy package, so this appears to add additional benefit on top of the therapies we already have, which is what’s exciting me the most at the moment.

It’s encouraging to hear how promising the trial results have been. The question everyone has, is how long might we be waiting for it to become available?  

Sotatercept has not been licensed anywhere around the world yet, and there is likely to be a bit of a delay before it’s licensed in the UK and is in widespread use.

What comes next is that NICE (the national body that makes treatment recommendations) will do an appraisal of the drug, starting in March next year (2024) and that will take a number of months.

This will involve them deciding what they think the added benefit of the drug is, balanced against its cost. So, we’re not there yet, but we would expect some decisions to start to be made in 2024.

Who will be eligible for this treatment if it’s made available?

We don’t know yet what the decision of the regulator and the reimbursing authorities will be, so we don’t know exactly where it will fit. However, it will be used within a group of patients that are similar to the group the drug was trialed in – so those with group one PAH.

It will likely be available for patients who are already on a significant amount of vasodilator drugs, most likely at least dual therapies. It will almost certainly be an ‘add-on therapy’ in that context.

Beyond that, we don’t know what the specific limitations will be and where it will fit in the treatment guidelines.

It’s important to remember that there are still some open questions, for example who the drug works best in, and how it should be administered. As a result of that, there are still ongoing trials across the UK that most of the specialist centres are signed up to.

If you are interested in being part of these trials, please speak to your PH team to see if you are eligible for them.

It sounds like there is a lot to feel positive about. Can you sum up why developments with this treatment should give people hope?

This is the first drug really that we’ve had in pulmonary hypertension that works by a different mechanism than all the vasodilators. It tells us that we can alter disease, beyond just opening the vessels up.

I expect there will be a subsequent generation of new drugs coming on the back of this. So, this will be the start of the next phase, or evolution, of how we treat patients.

I think we can be pretty optimistic that the last 20 years have seen a change in life expectancy and quality of life for patients, and in the next ten years and beyond we should be seeing further gains still.

I think what we’re talking about here is the capacity to do something different in this disease area and that is definitely a message of hope. It’s a really exciting time.

As we come to the end of this year, and the end of a difficult few years [with the pandemic], I think we’re in a much more hopeful position than we’ve been in for some time.

Watch Dr Iain Armstrong, Chair of the PHA UK, explain more about the NICE drug review process: