In a disease where many patients struggle with persistent pain and daily functioning, what do you see as the most critical goals for the next generation of endometriosis treatments?

I think what we need to find is something that probably works better for certain subgroups of endometriosis. It's unlikely that you'll find a drug that works for everyone. Right now, hormonal treatment, for example, still leaves about 30% of patients unsatisfied because it doesn't work for them. If we can identify specific subgroups and tailor treatment accordingly, that would be very helpful.
I believe that endometriosis is unlikely to be a single, uniform disease, as with other conditions. It probably has subdivisions, whether based on genetics, proteins, or other factors. That's one aspect. Then, there’s a need to find medications, surgical options, or other treatments with fewer side effects, which could increase acceptance among patients. Additionally, it's important to remember that these women are young and may be considering fertility at some point. Current treatments are usually contraceptive. So, if there is a non-hormonal option that can be safely given to patients trying to conceive, that would probably be a breakthrough.

In the future, what breakthroughs do you think could most accelerate innovation in this field?

There are currently no biomarkers that help identify patients who are struggling to determine whether they have the disease or to rule it out. Even if you had a marker that could predict disease recurrence or the effectiveness of a trial drug, as in the NOVA trial, there would still be challenges. Moving beyond just relying on pain and actually detecting changes in the disease remains difficult. Since many endometriosis lesions are hard to identify non-invasively, companies struggle to convince regulators that their drug genuinely inhibits the disease rather than just alleviating symptoms. Additionally, being able to predict the risk of recurrence or infertility would be highly beneficial, which is something we currently cannot do. Identifying subgroups in this context could also prove advantageous.

What makes you excited about the NOVA trial?

I think the main exciting point is that it's a non-hormonal approach, which I believe is very appealing to many patients because there's a lot of frustration with the current medications, including side effects and limited effectiveness for some. So, I find it exciting that companies are moving in this direction, and obviously, we'll see what results come out of it.

What is the central hypothesis behind the study?

The main idea is that endometriosis is a chronic inflammatory disease. The plan is to block one of the pathways involved in inflammation, specifically the prostaglandin E2, which has been shown to be upregulated in endometriosis tissue. Therefore, the goal is to selectively inhibit this pathway, which could help reduce the side effects we see with today’s pain medications. However, this remains to be seen.

What challenges have you seen in previous endometriosis studies? Have you been able to incorporate any learnings in this study?

The challenge is which patients to include in a study. The ones with suspected endometriosis or those with confirmed disease? If they're confirmed, it's usually patients who had a previous operation. You could argue that the disease may be different from cases that were never operated on before. So, that's one challenge. The alternative is to include patients with endometriosis visible on imaging, which often indicates extensive disease, but that isn't the case for most patients. That has always been an issue. That's why many studies include patients with a history of endometriosis, like those who had surgery within the last 10 years. But then, is it really endometriosis if they only have symptoms, or could it be more of a chronic pain condition? That's always a concern. In the past, most challenges involved hormonal treatments, which affected patients' ability to conceive, and sometimes caused typical hormonal side effects. Hopefully, with the NOVA trial, these issues will be reduced, as we will see. We've discussed these aspects extensively with the scientific advisory board and refined the protocol for the NOVA trial accordingly.

How do you expect the Phase 2 findings to guide the further development of vipoglanstat

First, we need to see if it works—that's important. Without that, nothing else matters afterward. However, that really depends on how and where it works. If it does, then we must evaluate how well, perhaps by examining subgroups within that cohort, and then design a Phase 3 trial if there's enough signal. That trial would likely need to be multi-center and international, probably extending beyond Europe. Additionally, the trial must be carefully planned with an adequate number of participants to increase the chances of success. In my view, this will largely depend on the results of the Phase 2 trial.

What initially motivated you to focus your research career on endometriosis?

In Berlin, where I trained, a colleague was establishing an endometriosis center at the hospital. I was preparing to leave Berlin for the US to study angiogenesis and antiangiogenic therapy, initially targeting cancer. Noticing similarities between cancer and endometriosis, I began investigating the latter. We developed a model based on principles from cancer research, which proved effective. After finishing a postdoc in the US and returning to Berlin, I moved to the UK to dedicate myself fully to clinical endometriosis, gaining access to patients and data.

What advice would you give to a young investigator entering the field of women's health today?

Well, firstly – good choice. My main advice is always to think a little outside the box and avoid sticking to the usual paths everyone has already taken, because otherwise we won't make progress. Also, look beyond your typical publications and explore different conditions to see what's happening there, and maybe consider how those insights could apply to endometriosis. Talk to people outside the medical field – chemists, geneticists, and others – and see how they view the situation. This could lead to new hypotheses. It's a highly prevalent disease, yet we still haven't fully understood or been able to control it.

Christian Becker, MD, is Professor of Reproductive Sciences, Co-Director of the Oxford Endometriosis CaRe Centre, and a Consultant Gynaecologist. Dr. Becker is the International Coordinating Investigator of the NOVA trial and a member of the Gesynta Scientific Advisory Board.