FDA Activity Recap: July 2024 Features Agency Program Announcements, a BLA Acceptance, Trial Design Feedback, and More

Last month, July 2024, the CGTLive^® team was diligently tracking the FDA's activities related to the development of cell and gene therapies for the treatment of rare, complex, and otherwise challenging diseases and disorders.

The agency has continued to ramp up its activities around these therapies as more of them progress through the pipeline in tandem. Last month proved no different, with announcements regarding the FDA's START Pilot Program and Center for Biologics Evaluation and Research (CBER)'s Interactive Site Tours Program, an acceptance of Mesoblast’s biologics license application (BLA) for remestemcel-L mesenchymal stromal cell therapy, and a few other important actions. Our team has highlighted these below.

Click the read more buttons for more details and information about each update.

Myrtelle’s Canavan Disease Gene Therapy Selected for FDA START Pilot Program

July 4, 2024 — Myrtelle Inc has announced that the FDA selected its investigational gene therapy, rAAV-Olig001-ASPA (previously known as MYR-101), for inclusion in its Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program. The viral vector-delivered therapy is in development for the treatment of Canavan disease (CD), a rare and fatal childhood genetic brain disease that occurs as a result of mutations in the ASPA gene.

The START program 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. Myrtelle’s rAAV-Olig001-ASPA was one of a few eligible CBER-regulated products, as it has shown “clinical benefit for rare diseases with unmet medical needs” and the company has shown “ability to accelerate development to market application,” according to the release. 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.

Nancy Barone Kribbs, PhD, the senior vice president of Global Regulatory Affairs at Myrtelle, said in a statement that acceptance into the program is “an honor” because of its recognition of rAAV-Olig001-ASPA as a potential treatment. “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,” she said.

FDA Accepts Mesoblast’s BLA for Remestemcel-L for Steroid-Refractory GvHD

July 23, 2024 — The FDA has accepted Mesoblast’s BLA for remestemcel-L mesenchymal stromal cell therapy, to be marketed as Ryoncil, for the potential treatment of steroid refractory acute graft versus host disease (GvHD).

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of January 7, 2025, for remestemcel-L.

“We are pleased that FDA has accepted our BLA resubmission for review, and look forward to the potential approval of RYONCIL for children with SR-aGVHD,” Silviu Itescu, MBBS, FRACP, chief Executive Officer and Managing Director, Mesoblast, said in a statement.

CBER To Conduct Interactive CGT Site Tours to Improve Communication, Share Best Practices

July 17, 2024 — The FDA has announced a Cellular and Gene Therapies Interactive Site Tours Program (the Interactive Site Tours Program) to improve communication and share best practices between industry and the regulatory agency.

The program will see regulatory managers from the Center for Biologics Evaluation and Research (CBER) touring biotechnology manufacturing facilities developing cellular and gene therapy products.

“With this program, CBER intends to enhance review efficiency and quality by providing CBER staff with a better understanding of the biotechnology manufacturing industry and its operations,” the Federal Register notice that the program was announced in stated.

Passage Bio Gets Positive Feedback From FDA on Plans to Test Gene Therapy PBFT02 in New Frontotemporal Dementia Indication

July 19, 2024 — Passage Bio has received positive feedback from the FDA regarding its plans to expand eligibility for its phase 1/2 upliFT-D clinical trial (NCT04747431), which is currently evaluating investigational gene therapy PBFT02 in patients with frontotemporal dementia (FTD) with GRN mutations (FTD-GRN), to patients with FTD with mutations in the C9orf72 gene (FTD-C9orf72).

Passage Bio received the feedback on the proposal to amend the upliFT-D protocol in the context of a Type C meeting process with the FDA. The company stated that attainment of the agency’s alignment on the matter was supported by preclinical evidence, along with efficacy and safety data from patients with FTD-GRN who were treated in the first cohort of upliFT-D. In light of the FDA’s feedback, Passage Bio intends to submit a revised trial protocol to relevant regulatory bodies and ethics committees shortly. Pending clearance, the company anticipates that it may begin dosing patients with FTD-C9orf72 in upliFT-D within the first half of next year.

Notably, both FTD-GRN and FTD-C9orf72 are associated with a pathological accumulation of transactive response DNA binding protein 43 in neuron cytoplasm. PBFT02, which utilizes an adeno-associated virus 1 vector, is intended to deliver a functional copy of the GRN gene, which encodes for the protein progranulin (PGRN). The gene therapy is administered via intracisterna magna injection with the intention of increasing levels of PGRN in the central nervous system.

FDA Recognizes Lomecel-B Cell Therapy for Alzheimer Disease Ahead of New Data

July 18, 2024 — The FDA has granted both Fast Track and Regenerative Medicine Advanced Therapeutic (RMAT) Designations to Longeveron's Lomecel-B investigational allogeneic medicinal signaling cell therapy for the potential treatment of patients with Alzheimer disease (AD).

“Fast Track designation is another important milestone for Longeveron and Lomecel-B™, which, along with the recent granting of RMAT designation, recognizes the critical need to quickly advance novel, safe and effective investigational treatments for AD, which has a devastating impact on patients and their families,” Wa’el Hashad, Chief Executive Officer, Longeveron, said in a statement. “AD is a neurodegenerative disorder that leads to progressive memory loss and death, and its tremendous impact on our aging population is exacerbated by a lack of therapeutic options that slow disease progression or improve cognitive function. We believe that Lomecel-B™, which demonstrated an overall slowing/prevention of disease worsening compared to placebo in the CLEAR MIND Phase 2a clinical trial, has the potential to become an important treatment option for physicians and patients, and we look forward to sharing the latest data with the Alzheimer’s Disease research and patient communities at AAIC 2024.”

Longeveron previously announced topline results from the phase 2a CLEAR MIND trial (NCT05233774) that demonstrated that it had met its primary end point of safety, with slowing of disease worsening in 50 patients aged 60-85 years old with a diagnosis of mild AD. At the end of the 39-week treatment period, investigators reported no new safety concerns, in addition to no cases of amyloid-related imaging abnormalities, clinically asymptomatic microhemorrhages on MRI, or notable changes in laboratory evaluations and electrocardiogram.