FDA Activity Recap: December 2024 Features New Approval, a Clinical Hold, and More

Last month, December 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 the FDA approving a new product for steroid refractory acute graft versus host disease (GvHD) and placing a clinical hold on a trial in Duchenne muscular dystrophy (DMD). Our team has highlighted these, and several other important actions, below.

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

FDA Approves Mesoblast’s Remestemcel-L for Steroid-Refractory GvHD

December 18, 2024 — The FDA has approved Mesoblast’s allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy remestemcel-L for the treatment of steroid refractory acute graft versus host disease (GvHD) in children aged 2 months or older.

Notably, the product is the first MSC therapy to have been approved by the FDA. It will be marketed under the name Ryoncil.

“Today’s decision marks an important milestone in the use of innovative cell-based therapies to treat life-threatening diseases with devastating impacts on patients, including children,” Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement.“This first mesenchymal stromal cell therapy approval demonstrates the FDA’s commitment to supporting the development of safe and effective products that could improve the quality of life for patients with symptoms that are unresponsive to other therapies.”

PepGen’s IND for Duchenne Muscular Dystrophy PMO PGN-EDO51 Placed on Clinical Hold by the FDA

December 17, 2024 — PepGen’s investigational new drug (IND) application for PGN-EDO51, an investigational phosphorodiamidate morpholino oligomer (PMO) intended to treat Duchenne muscular dystrophy (DMD), has been placed on hold by the FDA.

As such, the phase 2 CONNECT2-EDO51 clinical trial for PGN-EDO51, which is already active in the United Kingdom, may not yet go forward to with activities in the United States. PepGen pointed out that it has not yet received an official clinical hold letter from the FDA, but that the agency stated the letter will be provided within 30 days. The reason(s) for the clinical hold were not made clear in the company’s announcement of the FDA's decision. CONNECT2-EDO51 is a double-blind, placebo-controlled, multiple ascending dose study. PGN-EDO51 is also being evaluated in Canada in the separate open-label phase 2 CONNECT1-EDO51 clinical trial (NCT06079736).

“We intend to work closely with the FDA to address their questions on our application to initiate CONNECT2 as expeditiously as possible,” Paul Streck, MD, MBA, the head of research & development at PepGen, said in the press release. “Our open-label CONNECT1-EDO51 multiple ascending dose study of PGN-EDO51 in boys and young men living with DMD continues as planned in Canada. We have completed enrollment of the 10 mg/kg dose cohort; all 4 patients in this cohort have received at least 1 dose.”

SC291 CAR T-Cell Therapy Fast Tracked for Relapsed/Refractory SLE

December 4, 2024 — Sana Biotechnology’s investigational chimeric antigen receptor (CAR) T-cell therapy, known as SC291, has been granted fast track designation by the FDA for the treatment of relapsed or refractory systemic lupus erythematosus (SLE), including both lupus nephritis and extrarenal lupus.

Dhaval Patel, MD, PhD, the chief scientific officer of Sana, said in a statement that the company was pleased to receive the designation, noting that it “highlights the need for new treatment options for patients with relapsed/refractory SLE."

The therapy is a CD19-directed, hypoimmune (HIP)-modified allogeneic CAR T agent, designed as an off-the-shelf treatment. "As a HIP-modified allogeneic CAR T therapy with a scaled manufacturing process that produces hundreds of patient doses per manufacturing run, SC291 has the potential to serve as a universal off-the-shelf therapy that can address this large unmet need. We look forward to sharing initial data from the ongoing GLEAM trial," Patel said.

uniQure and FDA Reach Accord on Approval Pathway for Huntington Disease Gene Therapy AMT-130

December 18, 2024 — During a Type B meeting, the FDA and uniQure came into agreement regarding the use of an accelerated approval pathway for AMT-130, the company's adeno-associated virus (AAV) vector-based gene therapy currently being evaluated for the treatment of Huntington disease in 2 phase 1/2 clinical trials (NCT04120493 and NCT05243017).

Notably, the agency agreed that data from the ongoing phase 1/2 studies compared to external control natural history data will be sufficient to support a biologics license application (BLA), negating the need to launch another trial before submission. Furthermore, it was determined that for an accelerated approval the composite Unified Huntington’s Disease Rating Scale (cUHDRS) may constitute an intermediate clinical end point and that supportive evidence of clinical benefit can come in the form of data showing cerebrospinal fluid (CSF) neurofilament light chain (NfL) decreases.

“We are very pleased to reach agreement with the FDA on core components of an accelerated approval pathway for AMT-130,” Walid Abi-Saab, MD, the chief medical officer of uniQure, said in a statement. “Our alignment reflects the strength of our data and collaborative discussions with the staff and senior management at FDA’s Center for Biologics Evaluation and Research. This is an important milestone for the Huntington disease community as it puts us on the most rapid and efficient pathway to deliver a potentially life-changing therapy to people living with this devastating neurodegenerative disorder. We have initiated BLA readiness activities and look forward to further engaging with the FDA in the first half of 2025 to discuss our statistical analysis plan and the technical chemistry, manufacturing, and controls requirements.”