Why Ending Rh Disease Requires More Than A Breakthrough (Part 3 of 3)
By Ray Dogum, Chief Editor, Drug Discovery Online
This is part 3 of a three-part series on Rhogam and the effort to prevent Rh disease worldwide. Part 1 explains Rh incompatibility and how Rhogam helped protect my family. Part 2 examines the product’s unconventional development and the difficulty of replacing plasma-derived anti-D.
Throughout this series, I’ve used “Rhogam” as a common shorthand for Rho(D) immune globulin (RhIG). However, to be clear, Rhogam is the trademark owned by Kedrion Biopharma, so you can think of it as the “Listerine” [referencing the popular brand of mouthwash invented in 1879] of the Rho (D) immune globulin (RhIG) antibody market. It is widely regarded as the leading anti-D immune globulin brand in the U.S., although publicly available market-share data are limited.
A Fragile, Concentrated Supply Chain
What matters more than brand recognition is the supply. In the United States, there are only four licensed RhIG sources: Rhogam from Kedrion; HyperRHO from Grifols; Rhophylac from CSL Behring; and WinRho from Kamada.
That is a surprisingly concentrated supplier base for a product embedded in routine obstetric care, and it helps explain why even a localized manufacturing deviation or anti-D plasma disruption can quickly become a national clinical issue.
The products are clinically substitutable in many settings, but they are not identical in presentation or route of administration. Some are positioned primarily as intramuscular products, while others also support intravenous use, which matters during shortage management and in specific transfusion scenarios.
Guidance from the American College of Obstetricians and Gynecologists (ACOG) and Association for the Advancement of Blood & Biotherapies (AABB) has underscored that RhIG supply cannot be taken for granted: the market still depends on a narrow manufacturing base, plasma collection, and careful inventory stewardship. In other words, RhIG is not just a standard of care; it is a standard of care built on a dangerously fragile supply chain.
Donor Dependence and Manufacturing Constraints
Rhogam is also a case study in how CMC realities can be the product. Because Rhogam is plasma-derived, early developers had to solve problems that are now central to the biologics playbook: donor selection (high anti-D titers), fractionation and purification, potency assays and lot-to-lot consistency, and eventually virus inactivation/removal strategies and pharmacovigilance appropriate for a blood product.
In other words, “manufacturing” wasn’t a late-stage afterthought; it constrained the clinical program and shaped dosing, supply, and standards from the beginning. That is a very different innovation pattern than small-molecule medicinal chemistry, where supply is often scalable once the synthetic route is defined.
Plasma Derived Biologic and Downstream Productization
It is also worth being explicit about what “plasma-derived” means. RhIG starts with human blood donations: plasma is collected from screened donors, and manufacturers identify and use units with sufficiently high anti-D antibody levels, then pool plasma so a final lot can be made consistent. Depending on their location, some donors can be paid up to $500 per month. However, many countries, such as the UK, Australia, Japan, and France have outlawed paying donors for ethical reasons.
After donations are collected, the product must be productized into something clinicians can actually use, with defined potency (international units), stable formulation, sterile fill and finish, rigorous quality control and release testing, cold-chain handling, and clear labeling that ties dose to clinical scenarios such as routine prophylaxis versus larger fetomaternal hemorrhage. That downstream productization is not administrative polish, it is the difference between an intriguing biological phenomenon and a scalable, regulator-ready medicine.
Abundant Clinical Evidence
Clinically, RhIG’s value proposition is unusually obvious.
Obstetric guidelines summarize the impact in numbers. Postpartum RhIG reduced alloimmunization in at-risk pregnancies from roughly 13–16% historically to about 0.5–1.8%, and the addition of routine antepartum dosing reduced it further to around 0.14–0.2%.
That kind of effect is rare in modern development and helps explain why RhIG became embedded in standard of care. But it’s not standard care, everywhere.
Who Is Trying To Eradicate Rh Disease Globally?
First of all, Rh disease shouldn’t even be called a disease in my opinion. It is a normal immunological response to a blood type compatibility issue. And we have the technology that is ~99% effective to address this unwanted immunological response when administered properly.
Technically, we can’t eradicate Rh disease (or Rh incompatibility) the same way we eradicated something like the polio virus with vaccinations. However, according to the global nonprofit foundation, Worldwide Initiative for Rh disease Eradication (WIRhE), we can completely end the annual suffering and loss of at least 260,000 babies caused by Rh disease by investing in more education, developing robust clinical infrastructure, and fortifying the anti-D supply chain.
A few months ago, scientific and policy leaders from around the world gathered in Leiden, the Netherlands, for the 2nd annual international alloimmune conference on hemolytic disease of the fetus and newborn (HDFN). They shared key learnings, best practices, and urgent opportunities to tackle this global issue. The conference theme was “Let’s do something.” It was organized by Leiden University Medical Center (Netherlands), Sanquin (a Dutch blood supply and research organization), WIRhE, and African Initiative for Rh Disease Eradication (AFRICARhE).
RhD-mediated Disease Is Not The Whole Story
Krystalyn E. Hudson, Ph.D., associate professor of pathology & cell biology and co-director of the laboratory of transfusion biology at Columbia University, believes FcRn-targeting therapies could significantly expand treatment options for HDFN. Explaining the biology behind the approach, Hudson noted that FcRn "protects IgG from degradation" and also mediates the transfer of maternal antibodies across the placenta.
She highlighted the promising clinical results seen with the FcRn-blocking monoclonal antibody nipocalimab, describing how "all but one of the fetuses made it" and pointing to "the sheer number of reductions in intrauterine transfusions." Unlike RhoGAM, which is limited to RhD-mediated disease, Hudson emphasized that FcRn inhibition "covers the non-D-mediated HDFN" and "covers that other subset of women that would otherwise be unprotected."
Let’s Do Something
My final takeaway for drug discovery researchers reading this series is simple: do something. Share the issue, donate plasma, support groups expanding RhIG access, or help develop more reliably manufacturable monoclonal antibodies and other technologies that can strengthen today’s fragile anti-D supply chain. If you’re so fortunate to make big decisions at Roche, Siemens, Abbott, Amazon, JPMorgan, Morgan Stanley, or Goldman Sachs, evaluate Dr. John Gorman’s high finance deal with a heart.
If not for the scientists who pushed anti-D prophylaxis into clinical practice in the 1960s, my own children might not be alive today. And neither would 9 million other saved babies.
That history reminds us that discovery only matters when it reaches the people who need it. The next breakthrough may be close, but science alone will not close the Rh disease gap for women and babies around the world.
"A solved disease — still unsolved at global scale." – Dr. John Gorman