Fatigue, Quality of Life Improve With Rusfertide: Andrew Kuykendall, MD

Bringing this interview with Andrew Kuykendall, MD, clinical researcher at Moffitt Cancer Center, to a close, he addresses safety concerns that have been linked to the injectable hepcidin mimetic rusfertide (Takeda) and its overall impact on patient quality of life. Rusfertide is under investigation for treatment of polycythemia vera, a myeloproliferative neoplasm, in the ongoing phase 3 VERIFY trial (NCT05210790), on which Kuykendall is an investigator.

Previous segments of this interview focused on managing polycythemia vera, understanding hematocrit thresholds, reducing thrombotic risk, and reducing patient dependence on phlebotomy.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

What are some of the key safety considerations with rusfertide, and how does its tolerability compare with other treatments?

I often say that in our disease state, with myeloproliferative neoplasms, many patients do quite well for quite a long time. I think that's one of the fortunate things about this disease state. We're not really tolerant of any side effects at all, because we’re talking about patients living a long time, so even a small low-grade side effect, if you have to live with it forever, that's an issue. Fortunately, rusfertide is extremely well tolerated.

In the phase 2 study, we really didn't see too many high-grade side effects, and this was kind of evidenced by the fact that many patients stayed on study for a long period of time. Very few patients were coming off study; especially, we didn't see many patients come off due to side effects. The one side effect that we do keep an eye on is something that's not uncommon with subcutaneous injections, which is injection-site reactions. Interestingly, we're living in an era where subcutaneous injections are becoming more and more common for various different medications that are out there. Basically, I think there's an increased acceptance of this mode of administration.

But we do keep an eye on subcutaneous reactions, and we did see those with rusfertide. Now, most of these were very low grade; they tended to happen earlier during the disease course. But right now, all we know from the phase 3 trial [VERIFY] is that the adverse event profile was very similar to what we saw in phase 2. We'll always keep an eye on what's reported out and the severity of some of these things, but it didn't look like any new kind of adverse events or toxicity profile really played out in the phase 3 [trial] compared to what we've previously seen in the phase 2 [trial].

The injection-site reactions are the main thing that we saw. Again, the majority of these were grade 1, grade 2, and any SAEs [serious adverse events] that were reported out in the phase 3 [trial] were not deemed related to the drug. I think that's always very encouraging. We know that polycythemia vera patients actually have an increased risk of secondary malignancies, so we always keep an eye on secondary cancers. I think, quite encouragingly, what we saw, at least in the initial readout of this study, was that we did not see an increased risk of cancer in the rusfertide-treated patients. Actually, there were more cancer events that appeared to occur in the placebo group. The last thing we want to do is to be kind of contributing to some sort of secondary end point with a new agent, but fortunately we didn't see any evidence of that.

What do patient-reported outcomes from VERIFY tell us about rusfertide’s impact on fatigue and quality of life?

I will say, from my standpoint as someone who's seeing polycythemia vera patients all the time, the fatigue and some of the symptoms that go along with this disease is a problem. It is something that I think if you're in the community and you're seeing a lot of different diseases—colon cancer, breast cancer, pancreatic cancer—the symptoms that a polycythemia vera patient may come and report to you may not seem as extreme or they may not seem problematic when you're dealing with postoperative complications, huge surgeries, chemotherapy, things like that. But what I would say is that there's something that really affects these patients in a profound and durable and long-lasting way that make them not be the person that they'd like to be or that they were before this diagnosis. It really cannot be understated.

Even through all the advances we've made in understanding this disease process—we've had other drugs that have been approved for polycythemia vera—still patients continually come in saying that they're just not who they were before this. Whether that's from a fatigue that prevents them from doing what they want to do, whether it's just being tied to the health care symptom and that wears on them in some way, shape, or form, I think it's really important for us to incorporate these patient-reported outcomes into clinical trials, especially later-phase clinical trials where patients are blinded to the treatment they're receiving. This way we can actually kind of acknowledge the importance of these symptoms and really assess whether or not what we're doing is meaningfully improving quality of life for these folks.

The fact that we saw that there were improvements in fatigue and total symptom score with this type of an agent that we know already does something that's valuable in terms of reducing need for phlebotomy is, I think, super encouraging. It’s something that we're very excited about.