Ahead of Announcing Positive Results Seen in Trial for Gene Therapy FBX-101, Forge Biologics’ CEO Makes Comment Supporting Krabbe Disease’s Addition to RUSP

January 31, 2024

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Efficacy and safety results from the RESKUE clinical trial will be presented at at the WORLDSymposium 2024 on February 9.

Maria Escolar, MD

Forge Biologics, which is developing adeno-associated virus (AAV) vector-based gene therapy FBX-101 for the treatment of Krabbe disease, has announced that Timothy J. Miller, PhD, the CEO and president of Forge, made a comment during a public meeting of the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) on January 30, 2024, supporting the addition of Krabbe disease to the national Recommended Uniform Screening Panel (RUSP).¹ The company also noted that it will announce positive safety and efficacy data from the nonblinded, nonrandomized phase 1 phase 1/2 RESKUE clinical trial (NCT04693598) evaluating FBX-101 at the WORLDSymposium 2024, held February 4-9, in San Diego, California.

Krabbe disease is currently part of standard newborn screening in 11 US states. Two previous attempts were made to have it added to the RUSP, once in 2010 and once in early 2023, but neither attempt was successful. Although, the 2023 vote having ended in an unprecedented tie led to advocacy for the 2024 revote. The current standard of care treatment for Krabbe disease is hematopoietic stem cell transplantation (HSCT). Newborn screening increases the chances that children with Krabbe disease are able to receive treatment with HSCT before the onset of symptoms, which leads to improved outcomes.

“Inclusion of Krabbe disease on the RUSP would extend Krabbe Newborn Screening to 8 additional states, based on RUSP alignment legislation, ensuring that nearly 70% of all newborns in the United States are screened for this devastating disease,” Miller said in a January 29, 2024, statement.¹ “That would mean the potential of identifying dozens of babies every year, based on published incidence, who could receive the opportunity of life-saving treatments such as transplant and newly developing treatments like gene therapy.”

FBX-101 is intended to be administered after patients have already been treated with HSCT and is expected to improve peripheral neuropathy, a symptom of Krabbe disease that is not addressed by HSCT. Thus far, 5 patients, each of whom were identified via newborn screening, have received HSCT and subsequent treatment with FBX-101 in the RESKUE study. Forge Biologics stated that so far the combination of treatments has continued to demonstrate safety and efficacy.

Key Takeaways

Forge Biologics CEO, Timothy J. Miller, has expressed support for adding Krabbe disease to the national Recommended Newborn Screening Panel (RUSP) during a public meeting, aiming to extend newborn screening to 8 additional states.
The company will reveal positive safety and efficacy data from the phase 1/2 RESKUE clinical trial evaluating FBX-101 for Krabbe disease at the WORLDSymposium 2024.
FBX-101, an adeno-associated virus (AAV) vector-based gene therapy, aims to deliver a functional copy of the GALC gene to treat Krabbe disease, with promising results observed in patients treated in the RESKUE study so far.

“We continue to be encouraged by the safety and efficacy observed in FBX-101 treated patients,” Maria Escolar, MD, the chief medical officer of Forge Biologics, who will be presenting the data at the WORLDSymposium on February 9, added to the statement.¹ “The window of treatment for patients with Krabbe disease is very narrow and newborn screening is a critical step for these babies to benefit from any treatment, but unfortunately newborn screening for this devastating and quickly progressing disease is still only available in a handful of states. Dr. Miller’s comments to the ACHDNC will reflect the urgency physicians have been trying to convey for this patient community.”

FBX-101, which utilizes an AAV serotype rh10 vector, is intended to deliver a functional copy of GALC, the disease-targeted gene, which codes for an enzyme (GALC) that breaks down psychosine and some other sphingolipids.² Escolar previously presented results from the first 2 patients treated in RESKUE at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16 to 20, in Los Angeles, California.³ In an interview with CGTLive™ on the conference floor, Escolar noted that in the 2 patients, antibodies to the AAV vector had not increased beyond baseline. Escolar also highlighted that upon follow-up the treated patients showed motor function in the normal range and were observed walking independently.

“I've been working on this disease for over 20 years, and it is extremely exciting to see patients that are walking at this age,” Escolar said in the interview. “It is an amazing experience to be able to go from all the preclinical work to now seeing the effects in patients. I'm very excited and hopefully results continue to be good in the future.”

Notably, Forge Biologics is now a member of Ajinomoto Biopharma Services.¹ The acquisition was originally announced in November 2023, when Forge Biologics stated that it had entered into a $620 million all-cash deal to be bought by Ajinomoto Co., Inc.⁴

REFERENCES
1. Forge Biologics announces positive FBX-101 clinical trial update in patients with Krabbe disease identified by newborn screening ahead of RUSP vote. News release. Forge Biologics. January 29, 2024. Accessed January 30, 2024. https://www.forgebiologics.com/forge-biologics-announces-positive-fbx-101-clinical-trial-update-in-patients-with-krabbe-disease-identified-by-newborn-screening-ahead-of-rusp-vote/
2. Forge Biologics receives priority medicines (PRIME) designation from the European Medicines Agency (EMA) for novel gene therapy FBX-101 for the treatment of patients with Krabbe disease. News release. Forge Biologics. Accessed January 30, 2024.https://www.forgebiologics.com/2023/01/17/forge-biologics-receives-priority-medicines-prime-designation-from-the-european-medicines-agency-ema-for-novel-gene-therapy-fbx-101-for-the-treatment-of-patients-with-krabbe-disease/
3. Escolar ML, Vander Lugt M, Poe MD, et al. First in human RESKUE phase 1/2 clinical trial of intravenous FBX-101 (AAVrh10. hGALC) administered after immune and myeloablation for unrelated umbilical cord blood transplantation prevented immune responses, increased GALC activity, restored normal brain development, and normalized motor function in patients with infantile Krabbe disease. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #359
4. Ajinomoto Co., Inc. to Acquire Forge Biologics for $620 Million. News release. Forge Biologics. November 13, 2023. Accessed January 30, 2024. https://www.forgebiologics.com/ajinomoto-co-inc-to-acquire-forge-biologics-for-620-million1/