FDA Grants Nipocalimab Fast Track Designation for Rare Fetal Disease, with Katie Abouzahr, MD

Katie Abouzahr, MD

Credit: Johnson & Johnson

Nipocalimab, Johnson & Johnson’s investigational neonatal Fc receptor (FcRn) blocker, has recently been approved for a Fast Track designation by the US Food and Drug Administration (FDA) to reduce the risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) in pregnant patients. FNAIT occurs when the immune system of a pregnant individual attacks platelets in a developing fetus, leading to impaired clotting and bleeding. This rare condition poses significant risk to the fetus and newborn, sometimes leading to fetal death.

In an interview with HCPLive, Katie Abouzahr, MD, vice president of Autoantibody and Maternal Fetal Immunology Disease Area Leader at Johnson & Johnson, explains the transformative potential of nipocalimab for the treatment of patients with autoantibody-driven conditions like FNAIT and hemolytic disease of the fetus and newborn (HDFN).

HCPLive: What led to the development of nipocalimab as a potential treatment for this condition?

Katie Abouzahr, MD: Nipocalimab blocks the FcRn receptor and by blocking it, it does 2 things: It stops recycling Immunoglobulin G (IgG), and it reduces the amount of circulation. In pregnancy, it stops IgG, including harmful antibodies called alloantibodies, from crossing the FcRn receptor from mom to baby.

So, with that mechanism of action, you can imagine that anything that is caused by these antibodies is amenable to potentially treatment with nipocalimab as an FcRn blocker. There are so many diseases that are autoantibody-driven that we think about them in 3 segments: rare autoantibodies, the maternal fetal space, and prevalent rheumatologic diseases.

Nipocalimab is the only one being studied in all 3 of these segments, which takes us to maternal fetal immunology. So, what made us think about studying nipocalimab in this segment? Well, first, the actionable science is our guiding principle. If you can block the FcRn in the placenta, and you don't cross into fetal circulation, you're potentially stopping these alloantibodies from crossing the placenta and harming the fetus. And in the maternal fetal immunology, diseases of pregnancy, that is what happening.

There are no therapies approved in maternal fetal immunology for the treatment of these diseases. And these diseases, although rare, are devastating. There's very little that can be effectively done in a safe, approved, advanced therapy way. In FNAIT, in severe cases, it can cause intracranial hemorrhage or fetal demise. So, we have the actual science, we have the unmet need, which is unequivocal, and then we also think about value creation as a company. Those 3 things led us to really believe that we had a really unique FcRn blocker that had the properties that you need to have to go into maternal fetal immunology, where there's immense unmet medical need.

HCPLive: How does nipocalimab differ from existing treatment options?

KA: We are the only ones in maternal fetal immunology. So, the first thing is, is that you do want to think about an FcRn blocker that binds in a pH-independent way, which means that it binds to the FcRn receptor, and it doesn't fall off. And, we believe we have minimal transfer of nipocalimab into the baby, which is important. That's very important in all the indications, but it's critical for maternal fetal immunology.

The second thing is we have 2 patients, mom and baby, every single time. Added to that, there's no sort of proven regulatory pathway for us to follow. This is not us treading where many have been before us. This is us going somewhere important, but also new. And so, we do it with thought and care. Every single decision that we make is extremely judicious in terms of what we are doing, what it means, and the impact it will have.

The last thing I will say, though, is that there is a thread that links all these indications together, which is if one thinks outside of the maternal fetal immunology indications in and of themselves and go back to the rare antibody segment or the prevalent rheumatology segment, in those in the autoantibody space, approximately 80% of patients are women, with up to half of them of childbearing potential. We think that being able to show that we have data in pregnancy is important for patients as they're thinking about the treatments for these autoantibody driven diseases.

HCPLive: What were the key findings of the phase 2 UNITY trial that led to the FDA granting this Fast Track designation?

KA: There are 2 indications that we're looking at in this space. One of them is FNAIT, and that's where we received the Fast Track designation. But the other one that we're looking at is HDFN, where mom forms an alloantibody response to antigens on red blood cells. We had data from a phase 2 open-label trial in that disease. And although the diseases are not identical, they are considered analogous and similar enough that these data in HDFN then gave us reason to believe in moving forward directly to pivotal studies in fetal neonatal alloimmune thrombocytopenia. Because we're taking such care in how we go forward, we've worked incredibly closely with the regulators. And so we have previously received breakthrough designation on HDFN on the basis of those data and, in turn, Fast Track designation in the analogous disease of FNAIT.

HCPLive: How do you envision nipocalimab impacting the management and outcomes of this condition if it receives ultimately FDA approval?

KA: If it were to be successful, and if it were to receive approval, I hope it would accomplish what we get out of bed every day to do: transform the lives of patients and their families for the better. I mean, apart from the severity of it, which is cataclysmic, a lot of simply living through that is incredibly challenging.

The second thing is it's often late to be diagnosed and there are no diagnostic tests for FNAIT. In HDFN, for example, there are no therapeutic options that have been shown to be effective. Currently, it's essentially a transfusion where a needle is passed through mom's belly to treat baby, which is incredibly traumatic and high risk, even in the best of hands.

What we hope is that we'll be able to potentially bring something transformative, with a treatment that is non-interventional, safe, effective, and approved for treatment in this condition.

We feel incredibly strongly about the importance, not only for patients and their families living with these diseases, but also for the space in general and for the advancement of how we think about research in general.

HCPLive: Is there anything else that you would like our audience to know?

KA: We have so much passion around developing this program. In all 3 segments, we think that there is so much unmet medical need. I would like to recognize the teams who work so tirelessly to bring this medicine to patients. We really hope this will ultimately be transformative for patients and their families and I hope we get to continue the journey.