Five Advanced Therapeutics to Watch in 2025

In recent years, the FDA has continued to ramp up its activities around cell therapies, gene therapies, and other advanced therapeutics as more of them progress through the pipeline for the treatment of rare, complex, and otherwise challenging diseases and disorders. . This year is shaping up to continue the trend, with a number of Prescription Drug User Fee Act (PDUFA) dates already slated for the first quarter of 2025, and several other major FDA actions likely to occur later in the year. To kick off the new year, the CGTLive^® team has highlighted 5 notable therapies to keep an eye on as the year unfolds.

Click the read more buttons for past coverage of these therapies.

Fitusiran

Indication: Hemophilia A and hemophilia B

PDUFA: March 28, 2025

Fitusiran, an siRNA therapeutic targeting antithrombin being evaluated as prophylaxis in combination with appropriate bleed management guidelines in the ATLAS-OLE clinical trial (NCT03754790), enabled a lower number of infusions and lower doses of clotting factor concentrates (CFC) or bypassing agents (BPAs) to manage breakthrough bleeding in people with hemophilia A and hemophilia B. Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, recently presented these results at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California.

"Fitusiran is a highly effective prophylactic agent," Pipe told CGTLive®'s sister site, HCPLive®, at the conference. "The modulation of thrombin generation allows us to achieve effective bleed control with substantially lower doses of factor and bypassing agents, as well as fewer infusions. And this is just an overall better patient experience."

Vutrisiran

Indication: ATTR amyloidosis with cardiomyopathy (ATTR-CM)

PDUFA: March 23, 2025

The FDA previously approved Alnylam’s investigational subcutaneous RNA interface therapy vutrisiran, marketed as Amvuttra, for the treatment of transthyretin-mediated (ATTR) amyloidosis in June 2022. The approval of the therapy for this indication was based on positive 9-month results from the phase 3 HELIOS-A study (NCT03759379).

“We are pleased that the FDA has accepted our supplemental new drug application for vutrisiran for the treatment of ATTR with cardiomyopathy – a steadily progressing, debilitating and ultimately fatal disease,” Pushkal Garg, MD, the chief medical officer of Alnylam, said in a November 2024 statement. “In [the HELIOS-B clinical trial], treatment with vutrisiran improved cardiovascular outcomes, survival, disease progression and quality of life, as compared to placebo, in a population reflective of today’s patients on substantial background treatment. We look forward to working with the FDA to support their review of the application and bring vutrisiran to patients with ATTR-CM in the United States early next year.”

NT-501

Indication: Macular telangiecstasia

PDUFA: March 18, 2025

NT-501, Neurotech Pharmaceuticals’ encapsulated cell therapy implant, demonstrated a clinically meaningful change in the rate of progression in macular telangiectasia type 2, according to updated data from 2 phase 3 studies (protocol A, NCT03316300; protocol B, NCT03319849) reported in November 2022.

"We are extremely pleased to see these positive topline data for MacTel since there has been no pharmacological treatment to date," Richard Small, the chief executive officer of Neurotech, said in a statement at the time. "These findings are an important step towards giving hope to those currently suffering with unrelenting vision loss and who don’t have a way of stopping the progression of the disease today. We look forward to engaging with the FDA throughout the review process."

Prademagene Zamikeracel

Indication: Recessive dystrophic epidermolysis bullosa (RDEB)

PDUFA: April 29, 2025

Abeona Therapeutics' biologics license application (BLA) for prademagene zamikeracel (pz-cel; EB-101), an investigational autologous gene-corrected epidermal sheet therapy for the treatment of patients with recessive dystrophic epidermolysis bullosa (RDEB), was accepted for filing by the FDA in November 2024. Notably, the BLA is a resubmission, made by Abeona in October 2024 following a Type A meeting with the FDA that took place in August 2024 and in which the company reached an accord with the agency on necessary additional information pertaining to Chemistry Manufacturing and Controls (CMC).

“The FDA acceptance of our BLA resubmission moves us one step closer to providing pz-cel as a differentiated treatment option to address the persistent unmet needs of people with RDEB in the US,” Vish Seshadri, PhD, MBA, the chief executive officer of Abeona, said in a statement at the time. “We look forward to continuing to work with the FDA to finalize the review of the pz-cel application.”

Tabelecleucel

Indication: Relapsed/refractory Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disease (EBV+ PTLD)

PDUFA: Not set (previously January 16, 2025)

On January 16, 2025, the FDA issued a complete response letter (CRL) to Atara Biotherapeutics regarding its biologics license application (BLA) for tabelecleucel (tab-cel, also known as Ebvallo), an allogeneic Epstein-Barr virus (EBV)-specific T-cell immunotherapy, which was under evaluation for the treatment of relapsed/refractory EBV-positive post-transplant lymphoproliferative disease (EBV+ PTLD) in patients. Notably, the CRL was related to issues with a standard prelicense inspection of a third-party manufacturer for tab-cel rather than to any concerns regarding the efficacy and safety data contained within the BLA. The manufacturing process itself was not implicated, and the FDA has not requested additional clinical trials for tab-cel.

“We are working closely with our partner Pierre Fabre Laboratories, the FDA, and the third-party manufacturer to address the feedback to support marketing approval for EBVALLO,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a January 16 statement. “Once the third-party manufacturer GMP compliance issues have been adequately addressed, we will file for a resubmission, which we would expect to be potentially approved within 6 months of resubmission. Atara and its partner Pierre Fabre remain confident in the potential of Ebvallo and are committed to bringing this potential first-in-class medicine to United States patients with EBV+ PTLD who have limited treatment options and significant unmet need.”