If you've been managing your primary immunodeficiency disease (PIDD) with the same treatment for years, here's a heads-up: Your options could be expanding fast in exciting ways.
"Modern treatments have dramatically changed the outlook for many people with primary immunodeficiency," says Paula Henao, MD, medical director of the Immune Deficiency Foundation. Advances like targeted medications, gene therapy, and better immunoglobulin products mean that even people with some of the most severe PIDDs can live much longer, healthier lives, she says.
Here's a look at recent advances in treatment and diagnosis, as well as some possible game-changers ahead.
Newer Targeted Medications
Targeted drugs directly affect the specific genetic or immune signaling pathways – sequences of chemical reactions in a cell – that drive certain PIDDs.
Recently approved targeted drugs include:
Leniolisib (Joenja). The FDA in 2023 approved the first treatment specifically for a primary immunodeficiency disease called activated phosphoinositide 3-kinase delta syndrome (APDS). Leniolisib is a tablet for adults and children 12 and older, and it's currently being studied for use in younger children.
The drug blocks the overactive genetic signaling pathway that drives the disease, Henao says. Its most common side effects in clinical trials were headaches, sinusitis, and atopic dermatitis.
APDS is rare, but leniolisib's approval is important. It's a sign that in time, targeted medicines for other PIDDs will probably become available, says Christopher Brooks, MD, an allergy and immunology specialist at the Ohio State University Wexner Medical Center.
Mavorixafor (Xolremdi). In another recent advance, the FDA in 2024 approved the first drug specifically for WHIM syndrome. WHIM stands for warts, hypogammaglobulinemia, infections, and myelokathexis. The drug is a tablet for people 12 and older.
Mavorixafor helps release infection-fighting white blood cells from your bone marrow into your blood, boosting your body's ability to fight infections, Henao says. Its most common side effects in trials were low blood platelet counts, a rash, stuffy nose, nosebleeds, vomiting, and dizziness.
Strides With Gene Therapy
Gene therapy involves getting your own blood-forming stem cells corrected in a lab. The lab typically uses certain modified viruses to add missing or helpful genetic information to the cells. Then your health care team infuses the corrected cells back into your body.
Gene therapy is emerging as an option for people with certain severe PIDDs, especially when a matched sibling donor isn't available to provide stem cells for a transplant, Henao says. "For some patients, stem cell transplantation from a matched donor remains the best option. For others – especially when a suitable donor is not available – gene therapy may offer an alternative that avoids complications such as graft-versus-host disease."
One newer gene therapy is:
Etuvetidigene autotemcel (Waskyra). The FDA in 2025 approved this gene therapy for a primary immunodeficiency disease called Wiskott-Aldrich syndrome (WAS). It's an option for children 6 months and older and adults with the condition who have a change (mutation) in the WAS gene but don't have access to a matched, related stem cell donor.
This treatment can help the body make functional WAS protein and healthier immune cells – an important milestone, Henao says. Its most common side effects in trials included a rash, respiratory tract infections, febrile neutropenia (fever with a low white blood cell count), catheter-related infections, vomiting, diarrhea, liver injury, and tiny, red, flat spots on the skin called petechiae.
Better Immunoglobulin (Ig) Products
Immunoglobulin therapy is a medical treatment that uses antibodies collected from donated human blood plasma to help your immune system fight infection or disease.
Recent advances make it far safer and more convenient than in the past, Henao says.
Modern Ig products go through more advanced purification and viral inactivation processes, she says. And refined stabilizer additives and formulations help lower the risk of infusion-related symptoms like headaches, fevers, chills, or tiredness that some people got more often in the past.
In terms of convenience, use of subcutaneous Ig therapy – giving yourself injections at home – has expanded. "Instead of receiving larger intravenous infusions every three to four weeks, many patients can now administer smaller doses under the skin at home" once every week or two, Henao says. Your body absorbs medicine more gradually this way, which often leads to fewer system-wide side effects and more stable Ig levels.
Plus, doctors now have a wider range of Ig products to choose from, allowing them to tailor your treatment to your needs, she says.
The Potential of Gene Editing
One of the most promising frontiers for treatments of the future is gene editing, Henao says. Genes are segments of your DNA, and gene editing technologies like CRISPR, base editing, and prime editing let scientists directly repair errors in your DNA.
"CRISPR works like a molecular pair of scissors that can cut DNA at a very precise location, allowing the faulty gene to be corrected," she says. "Newer approaches, such as base editing and prime editing, are designed to be even more precise, allowing scientists to change specific letters in the genetic code without cutting the DNA in the same way."
In a clinical first, Henao says, researchers reported in late 2025 that they'd used prime editing in two people with a form of chronic granulomatous disease. That's a severe immunodeficiency caused by changes in the NCF1 gene. The researchers said the results showed enough promise to warrant more studies.
"This type of technology has the potential to repair disease-causing mutations in a patient's own stem cells so that the immune system can function normally," Henao says.
Most gene editing for PIDDs is done as part of clinical trials, Brooks says. But the trials are showing success, including increasing groups of patients, and "will likely lead to FDA approvals over the coming years," he says.
Other Promising Areas of Research
Henao also points to clinical studies that are looking into targeted immune therapies for disorders of immune dysregulation. In some PIDDs, she says, specific genetic defects cause your immune system to become overactive or poorly controlled. So researchers are testing out medications that block particular immune signaling pathways in an attempt to restore balance in the immune system.
Other studies are exploring new types of cellular treatments. One example, Henao says, is virus-specific T-cell therapy: "In this approach, immune cells that recognize certain viruses are grown in the laboratory and then given back to the patient to help control difficult infections."
If you want to find out whether any clinical trials might be right for you, you could start by talking with your immunologist. "Patients should ask a lot of questions. I think they shouldn't be afraid to find out what the latest and greatest" treatment or clinical trial is, says Niraj Patel, MD, an immunologist who treats primary immunodeficiencies in children and adults at Duke Health.
He says you can also learn about clinical trials through national advocacy groups (like the Immune Deficiency Foundation) and ClinicalTrials.gov.
Advances in Diagnosis
It takes an average of nine to 15 years to get diagnosed with a PIDD once symptoms start. And experts estimate at least 7 of 10 people with the condition have no PIDD diagnosis.
But the tide might be turning, slowly. Programs that test newborns for PIDDs have expanded. For instance, infant screening tests for a life-threatening disease called severe combined immunodeficiency (SCID) are now available in all 50 states, Henao says.
"Newborn screening allows affected infants to be identified shortly after birth – often before they develop serious infections – which allows treatment to begin much earlier and dramatically improves survival," she says.
Greater use of genetic testing also represents another big step forward. So far, researchers have pinpointed over 500 genes linked to PIDDs. "And every year, there are probably anywhere between 15 to 30 genes being discovered," Patel says. "Genetic diagnosis has improved our ability not only to make diagnoses sooner, but also to make new diagnoses of diseases that were unrecognizable or undefined or previously not known," he says.
What's more, doctors are becoming aware that simple laboratory findings can sometimes provide important clues that lead to earlier diagnoses, Henao says. For example, on a routine blood test, the finding of low levels of proteins called globulins could be a sign of an antibody (immunoglobulin) deficiency, which could prompt more testing.
"These advances are helping clinicians diagnose primary immunodeficiencies earlier and more accurately," she says.