With over 10 indications already being explored and the promise of more to come, it’s no surprise that Johnson & Johnson’s nipocalimab has been dubbed a “pipeline in a product.” It's a good thing, too, because the monoclonal antibody didn't come cheap.
Acquired as part of J&J’s $6.5 billion takeover of Momenta in 2020, the Big Pharma is clearly hoping to get its money’s worth. The anti-FcRn monoclonal antibody is currently undergoing midstage trials for the red-hot neurological disease area of myasthenia gravis as well as various immunologic conditions such as hemolytic disease of the fetus and newborn, rheumatoid arthritis, Sjogren's syndrome and lupus, to name a few.
Earlier this month, J&J’s pharmaceutical arm Janssen hit the primary endpoint in a phase 2 trial among alloimmunized pregnant adults at risk of severe hemolytic disease of the fetus and newborn. In a sign of nipocalimab’s versatility, it’s the only therapy in the clinic for this rare fetal condition.
What makes nipocalimab special is that it’s “playing in all three segments” of autoantibody R&D, Katie Abouzahr, M.D., autoantibody portfolio development leader at Janssen Research and Development, tells Fierce Biotech in an interview.
One of these segments is maternal/fetal, where many of indications are yet to have a single approved therapy. Then there’s rare autoantibodies, which is “probably the most crowded” area and includes conditions with a known pathogenic IgG antibody like myasthenia gravis, Abouzahr explains. Finally, there’s prevalent rheumatology, which unlike the other two segments isn’t dominated by rare diseases.
What unites the wide range of indications up for grabs is they are caused when the body’s immune system produces autoantibodies, which mistakenly target and react with tissues or organs. In the case of myasthenia gravis, it’s the body’s muscle proteins that come under attack, leading to muscle weakness and potentially severe breathing problems. Nicopalimab blocks the neonatal FC receptor (FcRn), meaning autoantibodies are more easily destroyed within cells.
If myasthenia gravis sounds familiar, that’s because Janssen isn’t the only company that wants in. Argenx already beat the healthcare behemoth to the finish line with FcRn blocker Vyvgart, which was approved by the FDA for generalized myasthenia gravis at the end of 2021. It arrived in a market that was dominated by Alexion’s—and now AstraZeneca’s—terminal complement inhibitor Soliris, which scored the green light for the same indication back in 2017. UCB has also filed for approval of two molecules for myasthenia gravis—zilucoplan and rozanolixizumab—while Sanofi recently dropped its own candidate, a BTK inhibitor called tolebrutinib.
With so much competition, how does Janssen expect nipocalimab to stand out?
Unlike Vyvgart, which is a fragment of human IgG1 antibody, nipocalimab is a full monoclonal antibody, meaning there is only a low likelihood of off-target effects, Sindhu Ramchandren, M.D., Janssen’s director of clinical development for neuroscience, points out.
“Some of the key differentiators which we're hoping to show through our trial is that with nipocalimab you're getting a very rapid onset of response,” she adds. “Within one to two weeks of starting a medication you should be able to see a response, which, as anybody who's been in this field long enough knows, is amazing because most of the current standard of care requires anywhere from several months to up to a year before you know that they're taking effect.”
By stretching the phase 3 trial out to six months, Janssen is also hoping to show that “not only do you see this early, deep response, but you're going to sustain it the longest with this molecule,” Ramchandren says.
Then there are the potential ways to administer the antibody subcutaneously. The benefit of being embedded within J&J is that Janssen can pair the therapy up with a “really differentiated device strategy,” says Abouzahr. “I still think we have best-in-class potential.”
Despite its high profile, myasthenia gravis is one of only two neurological conditions that nipocalimab is already in clinical trials for—the other being chronic inflammatory demyelinating polyneuropathy. But there is potential for more.
“There are definitely other neuro-immunologic diseases that are IgG autoantibody-mediated,” Ramchandren says. “We are in the information gathering and assessing phase right now to see: where else could we make an impact? Where else is there an unmet need that we can address?”
With the drug undergoing so many trials at once, there’s always a risk that one flop could cast a shadow over the other work. But Ramchandren isn’t too concerned.
“For so long we have had so few choices for many of these diseases—not just the neuroscience indications,” she says. “I think there's a cautious optimism that this class could fill in a very large unmet need, but not necessarily a blanket acceptance, of course, that it's going to work in all conditions equally.”
Despite straddling neuroscience and immunology, Abouzahr doesn’t feel that nipocalimab suffers from a lack of development focus as a result. “We see it actually as pathway driven, immune driven, autoantibody driven, more than we see it as anything else.”
So with a phase 3 trial in myasthenia gravis and midstage study in rheumatoid arthritis both set to read out this year, does Janssen still think Momenta’s hefty price tag was worth it?
“It was obviously a huge acquisition that I've been a part of since the day it closed,” Abouzahr says. “I think we're just really excited about nipocalimab, the science and the unmet needs.”