Advances in hemophilia gene therapy bring hope for pediatric patients

In the past three years, gene therapy has reshaped what's possible in hemophilia treatment for patients 18 and older. But a key question remains: How soon will these advances reach children?

At the 2025 American Society of Hematology (ASH) Annual Meeting, international hemophilia expert Guy Young, MD, Director of the Hemostasis and Thrombosis Center in the Cancer and Blood Disease Institute at Children's Hospital Los Angeles, delivered an invited talk on "Deconstructing Hemophilia Gene Therapy for Physicians."

A national leader in gene therapy, CHLA participated in both the Roctavian and Hemgenix trials and offers bopth of these specialized treatments to patients as young as 18. In addition, CHLA recently launched a phase 1 study of a next-generation gene-editing approach for hemophilia B.

Here, Dr. Young distills the current landscape-and the innovations that could potentially bring gene therapy to children with these disorders.

How today's gene therapies work

Two gene therapies-Roctavian for hemophilia A and Hemgenix for hemophilia B-are FDA-approved for males 18 and older.

Neither therapy is a cure, but patient outcomes have been overwhelmingly positive.

Hemgenix can bring patients' average factor IX levels into the upper 30% range, reducing bleeding and shifting them into the mild hemophilia category. For a first-generation product, that fulfills a lot of our goals."

Dr. Guy Young, MD, Director of the Hemostasis and Thrombosis Center, Cancer and Blood Disease Institute, Children's Hospital Los Angeles

With Roctavian, many patients achieve sustained factor VIII expression and can discontinue prophylaxis for months to years.

He notes that a common misconception is that these products directly replace the faulty factor VIII or factor IX gene with a natural copy. But that's not the case. Instead, both deliver a bioengineered factor gene into hepatocytes (liver cells) using adeno-associated viral (AAV) vectors.

New approaches, with promise for pediatrics

Despite the promise of these therapies, a major drawback is that they are not available for children. Both companies have discussed trials in older adolescents, but not younger children.

One of the key challenges is that today's hemophilia gene therapies rely on hepatocytes to pass on the instructions for factors VIII and IX.

"Liver cells don't divide much in adults, but they divide a lot in kids," says Dr. Young. "If you use this technology in a 2-year-old, it will have a massive dilutional effect over time as their cells divide. This is why a product like Hemgenix will likely never work in pediatrics."

CHLA is participating in a new phase 1 clinical trial that could eventually change that landscape. The therapy, called REGV131/LNP1265, was developed by Regeneron and uses a different approach: CRISPR-Cas9 gene editing to permanently alter the patient's DNA.

The trial is currently only available for patients 18 and older, but approved study protocols are already built for children as young as 2.

"This will absolutely be a staged expansion," says Dr. Young. "We need to prove safety and effectiveness in adults, then gradually move down to teens, young kids, and so on."

A cell-based strategy

CHLA will also soon open a phase 1/2 trial of a different novel agent-BE-101, a cell-based gene therapy for hemophilia B developed by Be Biopharma.

BE-101 takes a cell therapy approach-taking blood from the patient, isolating the B-cells, and inserting the gene for factor IX into those B-cells before reinfusing them.

"One benefit of cell therapy is that you could potentially titrate the dose and re-dose patients later if their factor levels dropped too much," explains Dr. Young "That's not possible with today's gene therapies."

BE-101 is only being tested in patients 18 and older. But because B cells divide far more slowly than hepatocytes in children, the therapy could hold future promise in pediatrics as well.

Looking ahead

To help more centers deliver hemophilia gene therapy, Dr. Young coauthored a 2023 paper- Opens in a new window outlining best practices for evaluating, treating, and monitoring these patients.

And while clinical trials in younger children remain years away, he is encouraged that the field is steadily moving toward solutions designed with pediatric patients in mind.

"When we talk about a chronic lifelong disease like hemophilia, we want to get to a cure as early as possible, so children are spared the irreversible effects that are otherwise inevitable over time," Dr. Young says. "That's what excites me most as a pediatric hematologist."