The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to Johnson & Johnson’s investigational monoclonal antibody (mAb) nipocalimab in alloimmunized pregnant individuals, according to a press release.
The therapy aims to reduce risk of fetal neonatal alloimmune thrombocytopenia (FNAIT) in these pregnant patients.
Nipocalimab has already received FDA Breakthrough Therapy designation for the treatment of individuals at elevated risk for hemolytic disease of the fetus and newborn (HDFN), which is frequently called the “red blood cell counterpart to FNAIT.”
In HDFN, the blood types of a pregnant person and her fetus are incompatible, which can potentially lead to the development of life-threatening anemia in the fetus/infant. In the rare disorder known as FNAIT, a pregnant individual’s immune system mistakenly attacks fetal platelets—a situation that can prove life-threatening to the fetus/newborn. The immune system develops antibodies against fetal/newborn platelet antigens, which are associated with the development of thrombocytopenia (low platelet counts).
The immune response observed in patients with FNAIT can be associated with bleeding and impaired blood clotting ability—both of which create a significant risk in the fetus/infant. When severe bleeding related to FNAIT occurs, it may be observed in the lungs, gastrointestinal tract, or eyes, which can lead to lifelong disability or even death. In fact, if there is a severe bleed in the brain, which is called an intracranial hemorrhage (ICH), lifelong neurologic issues or even death might occur. In as many as 26% of untreated pregnancies with FNAIT, ICH has been reported.
Currently, the phase 3 FREESIA is underway, with nipocalimab the sole investigational agent in clinical development for treating FNAIT. This mAb seeks to selectively block the neonatal Fc receptor (FcRn) and thus decrease levels of circulating immunoglobulin G (IgG) antibodies, including both alloantibodies and autoantibodies, which have been linked to a myriad of disorders.
When an agent receives Fast Track designation, this permits the manufacturer or the drug developer/ sponsor to communicate with and meet more often with the FDA. In the Fast Track program, the objective is to deliver new treatments to patients more rapidly. The program seeks to expedite the development and review timelines of agents that have shown the potential to treat serious, life-threatening conditions and to address unmet medical needs.
According to Katie Abouzahr, MD, Vice President, Autoantibody and Maternal Fetal Immunology Disease Area Leader at J&J, “Receiving Fast Track designation for nipocalimab in FNAIT underscores the urgency to address the unmet need for safe, effective, and targeted treatments to prevent FNAIT, a condition that could carry severe health consequences and even be fatal for the fetus or newborn.”
To date, nipocalimab is the only FcRn blocker that is being evaluated across three key sectors of the autoantibody space:
- Rare autoantibody disorders (eg, generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy)
- Maternal-fetal disease mediated by maternal alloantibodies (eg, HDFN)
- Prevalent rheumatologic disorders (eg, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease)
According to the press release, “Blockade of FcRn has the potential to reduce overall IgG[,] including pathogenic alloantibody levels[,] while preserving immune function without causing broad immunosuppression. Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.”
