How Upstream Biologics Could Transform CRSwNP Care: Joseph K. Han, MD

Verekitug (Upstream Bio), used to treat patients with chronic rhinosinusitis with nasal polyps (CRSwNP), was found not only to reduce nasal polyps in patients with this condition but also their overlapping asthma as well.¹

The data were presented at the American Thoracic Society (ATS) 2026 International Conference by lead study author Joseph K. Han, MD, chief of the Division of Allergy at Old Dominion University, and a patient with nasal polyps.

In this Q&A with The American Journal of Managed Care^® (AJMC^®), Han explained the importance of this potential drug in the treatment landscape for this condition and addressed important unmet needs in patients.

This transcript was lightly edited for clarity.

AJMC: How could targeting an upstream driver of inflammation potentially change the way clinicians think about managing CRSwNP compared with existing treatment approaches?

Han: This is my opinion only, but I think it's backed by a lot of evidence. I do think that, if you have respiratory diseases like asthma and chronic rhinosinusitis with nasal polyps, targeting upstream makes a lot of sense. I think this is where patients will likely do the best.

So, if you have a biologic that targets upstream, such as Thymic Stromal Lymphopoietin (TSLP) or the TSLP receptor—and verekitug specifically binds the TSLP receptor, not TSLP—when you block it at that level, we're starting to see evidence that you also block all the downstream cytokines, such as interleukin (IL)-5, IL-13, and IL-4.

The other biologics that we have target IL-5 or IL-4 and IL-13, but they don't block all of them. By blocking TSLP or the TSLP receptor, you're targeting much farther upstream, so you're able to block everything downstream. In a way, it's almost like giving multiple biologics at one time, which I think has led to higher efficacy based on the studies we've conducted.

AJMC: If future studies continue to demonstrate benefit, what impact could a therapy like verekitug have on reducing reliance on systemic corticosteroids or repeat surgical interventions?

Han: Chronic rhinosinusitis with nasal polyps is a quality-of-life disease, but it's a severe quality-of-life disease. Unfortunately, it hasn't received as much publicity as I think it should, as asthma has. We have 3000 to 4000 people die of asthma every year in the United States because of uncontrolled asthma. If you have uncontrolled nasal polyps, you also suffer significantly.

A lot of patients' partners who come in really have a hard time grasping just how significantly these patients are affected by their nasal polyps. One of the easiest ways I try to help patients' partners understand why nasal polyps are such a serious disease is by telling them to think about the worst cold they've ever had. Everybody has had a cold, and everybody knows what it feels like. You can't breathe through your nose, you can't sleep, and if you can't sleep, you're not functioning well the next day. Your physical tolerance and your mental tolerance are diminished significantly.

Well, that's what it's like for patients with severe chronic rhinosinusitis with nasal polyps. They can't breathe through their nose, they can't sleep, they can't function, and they're miserable.

Before the introduction of biologics, we tried to control this disease with good sinus surgery, topical steroids, and different ways of delivering topical steroids. But even then, we still didn't have good control of the disease, meaning these patients continued to have significant symptoms. As a result, we had to rely on systemic corticosteroids, and we hate doing that because we know—especially in women, who make up many of the patients with severe nasal polyps and asthma—that systemic steroids can have serious adverse effects on so many levels.

The introduction of biologics has been very helpful because they provide benefits similar to oral corticosteroids without many of the systemic adverse effects we see with steroids. It's encouraging that we now have this class of drugs, which is very effective for patients with severe, recalcitrant nasal polyps that are difficult to manage, allowing us to improve their quality of life.

AJMC: From a patient and provider perspective, how important is treatment convenience when managing a chronic condition such as CRSwNP, and what role could less frequent dosing play in long-term adherence?

Han: We talked about whether there is still an unmet need. Even with 3 biologics—now 4 biologics—approved for nasal polyps, why aren't we seeing that number go down to zero?

One of the reasons is the route of administration. Patients don't like receiving subcutaneous injections. They would much rather take an oral medication first or use an inhaler or a nasal spray. The least preferred mode of medication delivery is a subcutaneous injection.

So, if we're saying, "We can control your nasal polyps, but you have to get an injection every 2 or 4 weeks," a lot of patients have a hard time with that. Some patients are allergic to needles or don't want to receive injections.

In the VIBRANT study (NCT06164704), the phase 2 study, verekitug was administered every 3 months or every 12 weeks. By increasing the interval between subcutaneous injections, I think more patients may be willing to try this type of therapy.

AJMC: How do you envision upstream therapies fitting into the broader landscape of care for patients with overlapping inflammatory conditions?

Han: Asthma is highly associated with nasal polyps. In fact, the only comorbidity associated with chronic rhinosinusitis with nasal polyps that is more common than asthma is allergic rhinitis. Even though allergic rhinitis has a higher incidence than asthma in patients with CRSwNP, research has shown that asthma seems to have a greater impact on these patients.

Fortunately, much of the pathophysiology and many of the mechanisms that drive asthma and nasal polyps are very similar. I know because that's what I studied early in my career. We measured many of the inflammatory cells and cytokines involved in asthma and nasal polyps, and we found a great deal of overlap between the 2 diseases.

If that concept is true, then treating one of the inflammatory pathways involved in nasal polyps should also help treat asthma. That's exactly what we saw in the VIBRANT phase 2 study. We found that, in patients with both nasal polyps and asthma, verekitug improved nasal polyps while also improving asthma control and lung function.

I suspect the reverse will likely be true as well. There's a study evaluating verekitug in asthma, and I suspect that patients receiving verekitug for asthma who also have nasal polyps will likely see improvements in their nasal polyps, too.

AJMC: Looking ahead, what additional evidence would you like to see from future studies of verekitug before considering it a meaningful addition to the CRSwNP treatment landscape?

Han: The VIBRANT study was a phase 2 study, and we saw some of the best results, whether it was a reduction in nasal polyp score, improvement in nasal congestion, or improvement in sense of smell. We also recently presented data showing that verekitug had one of the best responder rates across those outcomes.

However, it's still only a phase 2 study, so it was conducted in a relatively small patient population. The next step is to conduct a phase 3 study in a much larger population. Based on the very positive results from the phase 2 study, we're now beginning the process of designing that phase 3 trial for patients with nasal polyps.

We also saw some very interesting biomarker findings, which I presented at the ATS meeting. We'll be following up on those biomarker data to better understand what they show.

One of the things I'm most excited about is evaluating off-treatment durability. In other words, what happens after patients stop taking verekitug? That's one way to differentiate among the biologics used to treat nasal polyps. We know patients do very well while they're receiving treatment, but the question is what happens after they stop. Does the benefit persist? That's something we're hoping future studies will help answer.