Atrasentan Has Promising Long-Term Potential in IgA Nephropathy: Richard Lafayette, MD, FACP

Atrasentan (Vanrafia; Novartis) was approved earlier this year, via the FDA’s accelerated approval pathway, for proteinuria reduction in primary immunoglobulin A (IgA) nephropathy. This was based on data, to date, from the phase 3 ALIGN study (NCT04573478). Richard Lafayette, MD, FACP, professor of medicine, nephrology, and director, Glomerular Disease Center, Stanford University Medical Center, ALIGN study investigator and steering committee member, previously spoke to the impact that IgA nephropathy has on the body, as well as primary and secondary outcomes data from the trial.

Here, he explains why a REMS program is not required for the endothelin A receptor antagonist and how patients may need to adjust—although he doesn’t see this conclusion coming to pass—should final ALIGN trial data fail to show a clinical benefit of atrasentan. This trial has an estimated study completion date of December 18, 2026.

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

Transcript

Why is a REMS program not required for atrasentan, and what does this mean in practice?

The REMS, the Risk Evaluation and Mitigation Strategies, by the agency are employed when they feel that the medication may put patients at risk for side effects that need to be actively monitored, actively discussed. Again, the safety profile of this agent is such that there is no REMS needed, so first, that talks to safety and tolerability. And then, in practice, it's really critical, because it makes it a smoother transition. The physician and the patient don't have to go online and sign up for a program. There's not a level of concern about safety that long discussions need to be had. Again, there have to be conversations about pregnancy avoidance with any of these more modern IgA nephropathy therapies, and particularly with endothelin receptor blockade. But the absence of REMS just makes it much smoother, easier, and denotes confidence by the agency at this point that the drug is safe and tolerable.

Is pregnancy contraindicated with atrasentan or is a washout period sufficient?

Well, pregnancy is certainly contraindicated on medication, so normally, we would give the patient enough time to, just as you suggest, wash out the medicine. Given the daily nature [of atrasentan], we'd probably want the patient off the medication for a good 2 weeks, and then if they are safe and desiring to go forward with pregnancy, that would be their option.

Should the ALIGN trial fail to confirm a clinical benefit in slowing kidney function decline, what could that mean for patients currently taking atrasentan?

Right now in the world of IgA nephropathy, there's been an explosion of medical development and new medication approvals, so we do have options to use medications by themselves, such as targeted budesonide, such as combining an ARB [angiotensin receptor blocker] and endothelin effect in the dual endothelin angiotensin receptor antagonist world. We have some complement blockers available as well. We do have options now. Again, I don't think anyone expects the GFR [glomerular filtration rate] signal to be anything but robust, given the degree of proteinuria reduction, and the ability of this agent in prior large trials to slow progression in diabetic kidney disease is supportive as well—so we'll hope that doesn't happen.

But if it were, a lot of people would be disappointed. Fortunately, patients who, and clinicians who, buy in early to use the medications, the downside and harm risk is extremely low, and there will be other options to come forward. But again, it's certainly not anybody's expectation. We do have to keep in mind—again, just me giving my opinion—that even at the early steps for accelerated approval, the agency looks at all the data, at that time period, at 9 months, and there'll be patients from 9 months to even further along in the trial to see if the overall profile is one that supports the approval, including the impact on kidney function.

It must have been a very nice package. Again, we're only able to look at the proteinuria and safety data so far. But I'm extremely optimistic that this will be good for our patients.