Myrtelle’s Canavan Disease Gene Therapy rAAV-Olig001-ASPA Decreases N-Acetylaspartate Levels in Phase 1/2 Study

Myrtelle’s rAAV-Olig001-ASPA (MYR-101), an investigational recombinant adeno-associated virus (rAAV) vector-based gene therapy intended to treat Canavan disease (CD), has decreased levels of the key biomarker N-Acetylaspartate (NAA) in new data from a phase 1/2 clinical trial (NCT04833907).¹

According to the company, cerebral spinal fluid (CSF) analyses from 7 patients treated in the study, who had follow-up of up to 24 months posttreatment, showed reductions of more than 80% in NAA levels from baseline in all 7 patients. Furthermore, brain white matter and myelin volume increases during the same time intervals were seen on MRI. In addition, functional improvements on validated functional scales were also recorded, in contradistinction to the deterioration that would be expected in untreated CD.

“The combination of changes in NAA levels and myelin volume offers a valuable tool for assessing early therapeutic efficacy in CD,” Olga Flamini, PhD, the cochief medical officer at Myrtelle, said in a statement.¹ “Improvement in such important disease markers like NAA and myelin, together with functional gains in our patients, is encouraging given the progressive nature of CD. It drives us to continue our work to bring this potentially important therapy to the patients who currently do not have treatment options.”

In June of this year, the FDA selected rAAV-Olig001-ASPA for inclusion in its Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program, which is intended to facilitate efficient communication between sponsor and agency staff to aid in completion of regulatory milestones and to speed up the development of promising therapies.² rAAV-Olig001-ASPA was 1 of a few eligible products regulated by the Center for Biologics Evaluation and Research (CBER), as it has shown “clinical benefit for rare diseases with unmet medical needs” and Myrtelle has shown “ability to accelerate development to market application.” The communication between the 2 entities will go beyond the standard available formal meetings—occurring on an ad hoc basis—with an aim of reducing wait times associated with the formal FDA meeting process.

“Acceptance into the START pilot program is an honor in that it recognizes rAAV-Olig001-ASPA as a candidate for accelerated development as a potential treatment for CD,” Nancy Barone Kribbs, PhD, the senior vice president of global regulatory Affairs at Myrtelle, said in a June 2024 statement.² “Opening the lines of communications beyond traditional meeting pathways provides the opportunity to quickly address development issues that would otherwise delay progression to market application. We are encouraged by the opportunity to facilitate the development of a potential treatment for Canavan children who are without treatment options.”

In addition to inclusion in START, the FDA has also granted AAV-Olig001-ASPA regenerative medicine advanced therapy (RMAT) designation, orphan drug designation (ODD), rare pediatric disease designation, and fast track designation.¹ The European Medicines Agency has granted the therapy ODD and advanced therapy medicinal product classification.

rAAV-Olig001-ASPA is not the only AAV vector-based gene therapy currently in development for CD. BridgeBio Pharma’s BBP-812, an AAV9 gene therapy, is currently being evaluated for the treatment of CD in the phase 1/2 CANaspire clinical trial (NCT04998396).³ Notably, on September 10, 2024, BridgeBio announced that the FDA had granted BBP-812 RMAT designation based on data from CANaspire. In particular, the data constituted 12 months of safety and efficacy findings that pertained to the first 8 patients treated in the trial. All of these patients achieved a decrease in NAA in the urine and central nervous system to levels typically seen in mild disease.

“CD 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.³ “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 CD and their families.”

REFERENCES
1. Myrtelle announces significant reduction in N-acetylaspartate (NAA), a key biomarker, in patients treated in its phase 1/2 clinical trial of the investigational gene therapy rAAV-Olig001-ASPA for Canavan disease. News release. Myrtelle Inc. October 1, 2024. Accessed October 2, 2024. https://myrtellegtx.com/myrtelle-announces-significant-reduction-in-n-acetylaspartate-naa-a-key-biomarker-in-patients-treated-in-its-phase-1-2-clinical-trial-of-the-investigational-gene-therapy-raav-olig001-aspa-for-cana/
2. Myrtelle announces that the FDA has selected rAAV-Olig001-ASPA gene therapy candidate for the treatment of Canavan disease for the support for clinical trials advancing rare disease therapeutics (START) pilot program. News release. Myrtelle Inc. June 5, 2024. Accessed October 2, 2024. https://myrtellegtx.com/fda-selects-myrtelle-for-start-pilot-program/
3. 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 October 2, 2024. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-receives-fdas-regenerative-medicine-advanced-therapy