IBD's Most Persistent Gap: Q&A with Christian Thienel

In 2024, Pharmaceutical Executive reported on a survey that showed a significant number of patients suffering from irritable bowel disease (IBD) struggle to afford proper healthcare. According to the results, treatments became unattainable due to barriers such as financial challenges and insurance issues. Many patients also struggled with adverse health impacts.

At the time, the Crohn's & Colitis Foundation president and CEO Michael Osso said, “These findings underscore the urgent need to address healthcare disparities in IBD care. Despite our progress in IBD research and treatment options, many patients still struggle to access the care they need without facing undue burden. Our survey findings highlight the critical need for reforms to ensure that IBD patients can access the medications they need without undue financial hardship."

Recently, Pharmaceutical Executive spoke with Christian Thienel, director at Back Bay Life Science Advisors, about the ongoing issues with IBD treatments. While the original survey focused more on the financial barrers, Thienel’s conversation looked at treatment and R&D barriers which allow for persistent unmet needs to impact patients.

Click here for the video interview!

Pharmaceutical Executive: Is there a persistent unmet need for new therapies for IBD?
Christien Thienel: Ulcerative colitis and Crohn's disease are two of the most active therapeutic areas in all of biopharma, and they have attracted significant investment from both large pharma and smaller biotech. When people think about IBD treatment today, they think about Humira, Remicade, and increasingly Rinvoq and other JAK inhibitors. But historically, injectable therapies have dominated the landscape.

Opinions on how effective and safe those products are vary depending on who you ask. Generally speaking, physicians are relatively satisfied with TNF inhibitors in this space. But particularly in Crohn's, and to a meaningful extent in UC as well, those therapies are not altering the course of the disease. They represent a major advance over the older generics used in this population for many years — but one of the key findings from the research we did going into this paper is that substantial unmet need persists around what to do beyond a TNF inhibitor. Options for effective mechanisms of action beyond that class remain limited.

The landscape has expanded somewhat. Integrins like Entyvio and several other products offer comparable efficacy to TNF inhibitors. But the need that really persists is an oral product that balances efficacy and safety in a way that currently doesn't exist in this space. That product doesn't necessarily need to match biologic-level efficacy — it could potentially be somewhat less efficacious — if it offers a meaningfully improved safety profile to support that trade-off.

There's been a lot of excitement around Rinvoq, and commercially it has been extremely successful. But one of the consistent findings from our KOL interviews and the survey we commissioned was significant concern about the black box warning and the safety profile associated with JAK inhibitors more broadly. So the unmet need we see is clear: something with biologic-like efficacy but an improved safety signal. And the oral delivery advantage remains a major differentiator in this space, where very few options currently exist.

PE: When treating IBD, what are the restraints with JAK inhibitors?
Thienel: JAK inhibitors have been around for quite a while, and they are understood to be highly effective. The JAK-STAT pathway has a well-established role in autoimmune and inflammatory diseases — it is one of the most direct and well-characterized mechanisms in a space that attracts significant attention from large pharma.

Rinvoq — upadacitinib, AbbVie's product — has been very successful in IBD. It has strong data for inducing and maintaining clinical remission, and the oral delivery is a meaningful advantage. But what comes up consistently in our research is the safety concern — not just with Rinvoq specifically, which in many ways has a better safety profile than earlier JAK inhibitors, but with JAK inhibition as a class. There is a perception problem among physicians: JAK inhibition carries baggage from an adverse event standpoint that is difficult to separate from any individual product.

Rinvoq carries boxed warnings for cardiovascular adverse events, malignancy risk, and infection risk. And there have been other JAK inhibitors in this space that have faced regulatory challenges or significant labeling updates related to adverse events. That history colors how physicians think about the class as a whole.

What came through very clearly across our research is that if there were an oral product that matched Rinvoq's level of efficacy without those safety concerns, it would be a clear winner in this space. That said, Rinvoq is doing very well — it has grown tremendously in IBD, which speaks to the depth of unmet need for oral options in this space. Even with its limitations, it is used extensively and has an important clinical role. Virtually all of the KOLs we spoke with use it and are relatively satisfied with it. But awareness of the cardiovascular and broader safety risks remains acute, and that concern is consistently top of mind.

PE: What advancements are being made for oral treatments of IBD?
Thienel: There are a number of emerging mechanisms worth discussing. We cover SIK2 inhibition in some depth in the paper — that's the mechanism Nimbus is working on — and I think it has some distinctive advantages. It not only reduces the activity of pro-inflammatory cytokines, but also has an effect on IL-10 and a mucosal healing mechanism that I think is a missing piece in a lot of the single cytokine-based approaches available today.

Oral IL-23 inhibitors are also generating real excitement, particularly with the recent approval of icotrokinra. The IL-23 mechanism is very well validated in the space, and the efficacy and safety data have been impressive. That said, as we've seen with the injectable IL-23 inhibitors, the single cytokine approach may not solve all the problems. My hunch is that it probably won't — but icotrokinra is nonetheless expected to be a very successful product.

There are also microRNA regulators discussed in the paper that have shown some interesting clinical signals, and TYK2 inhibitors have progressed considerably. The TYK2 program that Nimbus developed with Takeda is primarily advancing in psoriasis as a lead indication, but there has been meaningful development activity around the TYK2 pathway in IBD as well.

There is clearly a lot of activity in this space, which reflects what we saw from the market research: the unmet need on the oral side is significant. The question is which of these mechanisms will best address what we believe are the fundamental remaining gaps — and each has its own set of advantages that will play out in the clinic.

PE: What significant umet needs remain in IBD treatment?
Thienel: You might assume that with the number of therapies available, this is a relatively well-served market. But one of the most consistent findings from our research is that it isn't. There are therapies that can induce clinical remission after initial treatment — but durability of remission remains a significant unmet need. A large number of patients are still cycling through multiple therapies, which is itself a signal that new mechanisms of action and new delivery methods are needed. Having additional options remains important precisely because durable efficacy continues to be a challenge.

If a patient with IBD has tried three or four different biologics or advanced therapies and hasn't achieved sustained remission, there are essentially no remaining options that physicians can confidently recommend at this point. So there is still considerable room to improve on efficacy — and specifically on rates of durable clinical remission.

We're also seeing growing interest in mucosal healing as a distinct therapeutic goal. As I mentioned earlier, single cytokine approaches are effective at reducing inflammation and producing an initial response. But there is a growing perception among GI KOLs — and I'll acknowledge this is somewhat speculative — that addressing mucosal healing more directly, including restoring barrier function and addressing elements of the disease that aren't as directly targeted by individual cytokines, could be the key to achieving more durable responses and meaningfully improving patient quality of life. Those components of the disease state are increasingly seen as important, and they remain underaddressed by the current standard of care.