BridgeBio Pharma Garners FDA RMAT Designation for BBP-812

Florian Eichler, MD

BridgeBio Pharma’s BBP-812, an investigational adeno-associated virus serotype 9 (AAV9) vector-based gene therapy intended to treat Canavan disease, has received regenerative medicine advanced therapy (RMAT) designation from the FDA.¹

The gene therapy is currently being evaluated in the phase 1/2 CANaspire clinical trial (NCT04998396), and the agency made its decision to grant the designation based on data from the study. In particular, the data constituted 12 months of safety and efficacy findings that pertained to the first 8 patients treated in the trial.

According to BridgeBio, improvements in functional outcomes were observed in all patients who had 1 or more follow-up examinations. Given examples of functional outcomes included head control, sitting upright, reaching for and grasping objects, and visual tracking. Furthermore, all of these patients achieved a decrease in N-acetylaspartate (NAA) in the urine and central nervous system to levels typically seen in mild disease. In terms of safety, the company characterized the gene therapy as “well-tolerated” and noted that its safety profile was “generally consistent” with that seen in AAV9 gene therapy programs.

“Canavan disease is an extremely rare and rapidly progressive neurodegenerative disease that prevents most children from meeting basic developmental milestones, such as crawling, walking, speaking, and even holding their heads up,” Kathleen Flynn, BA, the chief executive officer of National Tay-Sachs & Allied Diseases Association, said in a statement.¹ “It is a terminal diagnosis with no approved treatment to date. The news of the RMAT designation, coupled with the preliminary results seen in the clinical trial, provides hope to children worldwide living with Canavan disease and their families.”

Previous designations granted to BridgeBio by the FDA for BBP-812 include orphan drug designation (ODD), rare pediatric disease designation, and fast track designation. The gene therapy also received ODD from the European Medicines Agency.

“We are honored to be granted RMAT designation for BBP-812 and are eager to work closely with the FDA and the Canavan community with the goal of bringing our therapy to families living with Canavan disease as fast as possible,” Eric David, MD, JD, the chief executive officer at BridgeBio Gene Therapy, said in a statement.² “We are beyond grateful to the children and their families who are participating in CANaspire, as well as to the study investigators. RMAT will allow us to work more closely with FDA to ensure we are responding to the urgency that families feel.”

CGTLive® previously spoke to Florian Eichler, MD, a neurologist at Massachusetts General Hospital, who presented data from CANaspire at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.² In addition to discussing the most recent findings from the trial at the time, Eichler also spoke about the importance of early diagnosis and newborn screening for rare inherited diseases like Canavan disease, particularly as gene therapy clinical trials for these indications become more prevalent.

“I think for the general practitioner, or the neurologist, who might be seeing these kinds of patients: early identification is key,” Eichler told CGTLive. “There are now trials that are available that are delivering safely a healthy copy of the gene. This has the potential to really allow for some of these children to attain milestones that have never been seen before. But it all requires a timely diagnosis and referral to trial sites. And we're hoping that in the future this [trial] will lead to an eventual approval, but we're still years away from that.”

Eichler also presented data from a natural history study, CANinform (NCT04126005), which is running in parallel to CANaspire and meant to inform the selection of end points.² Eichler pointed out that there are currently no validated scales for Canavan disease, but that the data from the natural history study is intended to allow for examination of the relationship between NAA levels and disease severity.

REFERENCES
1. BridgeBio receives FDA’s regenerative medicine advanced therapy (RMAT) designation for BBP-812 Canavan disease gene therapy program. News release. BridgeBio Pharma, Inc. September 10, 2024. Accessed September 12, 2024. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-receives-fdas-regenerative-medicine-advanced-therapy
2. Eichler F, Nagy A, Laforet G, et al. Initial biomarker and clinical findings from the CANaspire Canavan disease gene therapy trial: Exploration of connections between NAA and disease severity. Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA. Abstract #358.