Nipocalimab

Last week, the FDA granted fast track status for Johnson & Johnson’s investigational monoclonal antibody nipocalimab in the rare blood disorder FNAIT. Just once in history has a drug been approved in maternal fetal immunology, specifically in hemolytic disease of the fetus and newborn (HDFN). “And it was approved in 1968," says Katie Abouzahr, M.D., Johnson & Johnson’s vice president and autoantibody and maternal fetal immunology disease area leader, in an interview with Fierce Biotech. “That program was revolutionary." The drug is Rh immunoglobulin (RhoGAM), a medication used to manage and treat Rh-negative pregnancies, which is when the mother’s immune system treats Rh-positive fetal cells as if they were foreign cells and destroys them. The blood product is delivered by intramuscular injection to prevent individuals from forming the alloantibodies that cause HDFN. RhoGAM was originally discovered by J&J and now sold by Kedrion.  Now, more than 50 years after RhoGAM’s approval, the J&J leader is hoping to build off the pharma’s legacy and bring another maternal fetal immunology treatment to market. “The unmet need is unequivocal,” Abouzahr said. Last week, the FDA granted fast track status for J&J’s investigational monoclonal antibody (mAb) nipocalimab in another rare blood disorder called fetal and neonatal alloimmune thrombocytopenia (FNAIT). According to J&J, nipocalimab is the only investigational therapy currently in clinical development to treat the potentially life-threatening condition in which a pregnant person's immune system attacks fetal platelets and subsequently runs the risk of severe bleeding complications for the baby. The fast track designation follows a phase 2 proof-of-concept data drop for nipocalimab in HDFN, an alloimmune disease of pregnancy that has a similar disease mechanism to FNAIT.       The mAb is designed to block IgG binding to FcRn in the placenta and prevent transfer of maternal alloantibodies to the fetus. The investigational therapy also previously snagged orphan drug designation in FNAIT, an indication in which no approved therapies specifically designed to solely manage the condition exist. The freshly obtained fast-track status is for alloimmunized pregnant people at risk of FNAIT. The agency’s tag is made to speed up timelines related to drug development and the review process.       “These are desperate situations,” Abouzahr said, explaining that severe cases of FNAIT can lead to intracranial hemorrhage and even death for the newborn. “It's rare but it's cataclysmic for these families.” FNAIT often occurs in a person’s first pregnancy and there isn’t any routine screening conducted for the alloantibodies that cause the condition, Abouzahr said. That means diagnoses aren’t delivered until a FNAIT pregnancy or birth occurs. So, what options do patients have? “If you've got access to a good center—a specialized center that can handle this—treatment can include intravenous immunoglobulin, so IVIG with or without steroids, because you're trying to suppress this immune response,” Abouzahr said. But IVIG comes with several challenges. “IVIG hasn't been studied for approvals. There are no clinical trials; people use all different doses because there's no sort of agreement around it,” the J&J leader explained. The pooled antibody treatment has black box warnings—the FDA’s warning to consumers that a product could cause serious adverse reactions that could lead to severe injury or even death.     The Big Pharma is currently testing the mAb among alloimmunized pregnant individuals with FNAIT in a pivotal phase 3 program, according to the company. More information on the global FREESIA trial will be available in the coming weeks when the study’s listing will go up on ClinicalTrials.gov, according to Abouzahr. But J&J isn’t limiting nipocalimab just to maternal/fetal diseases. The New Jersey-based pharma giant believes the investigational therapy could hold the answer for dozens of conditions. “This FcRn blocking approach has the potential to affect any autoantibody-driven disease—there are maybe around 80,” Abouzahr said. J&J splits up these diseases across three segments: rare autoantibody, maternal/fetal and prevalent rheumatology diseases. The company is currently evaluating nipocalimab in a handful of trials that fall under those three umbrellas, including generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, idiopathic inflammatory myopathies, rheumatoid arthritis, Sjögren's disease and systemic lupus erythematosus.  We're going for this. No one else has. Yes, it is more challenging. There's no trodden path that we can follow for regulatory approval." — Katie Abouzahr, M.D. J&J acquired nipocalimab back in 2020 when Momenta Pharmaceuticals was bought out for $6.5 billion. The deal secured J&J a challenger to now-approved drugs from Argenx (Vyvgart for generalized myasthenia gravis) and UCB (Rystiggo also in myasthenia gravis). While other companies have gone after FcRn blocking, no one else has publicly disclosed any attempts in the fetal/maternal category. “We're going for this. No one else has,” Abouzahr said. “Yes, it is more challenging. We're studying two patients every time. There's no trodden path that we can follow for regulatory approval. And it's an incredibly important and delicate area that we want to approach with the care, the respect, the thought that it requires. But I almost feel like we have a duty to go forward, given we have an investigational therapy that could potentially be transformative.” Editor's note: This article was updated at 1:30 p.m. ET on April 2 to clarify RhoGAM's current therapeutic uses.