Cell & Gene Therapies

Regenerative medicines using expedited review pathways dominate novel approvals at the Center for Biologics Evaluation and Research, while the Center for Drug Evaluation’s higher volume comes with lower first-cycle approval rates and more standard reviews.

Marketing authorization applications for five new advanced therapy medicinal products were filed with the European Medicines Agency in 2024, the highest number in any year since 2020. The Pink Sheet looks at these and two other ATMPs that might get the thumbs up from the European Medicines Agency in 2025.

Amid complaints about the challenges of following gene therapy patients for up to 15 years, OTP Director Nicole Verdun said the FDA is considering how to conduct long-term postmarket studies more efficiently.

China has granted its first approval for a stem cell therapy, to domestic firm Platinum Life Biotech’s umbilical cord-derived mesenchymal stem cell product for corticosteroid-failed acute graft-versus-host disease with gut involvement.

If successful, the new CMS cell and gene therapy access model eventually could expand to oncology or hemophilia products, an Avalere Health expert said.

“Significant progress” has been made in setting up the UK’s Rare Therapies Launch Pad pilot scheme, which will construct a “new regulatory pathway tailored specifically for ultra-rare diseases,” a senior scientist involved in the project says.

Himal Thakur said the required long-term safety study can replicate a clinical trial, which is not the intent.

A Catalyst fix, a pediatric rare disease voucher reauthorization that should prevent future workload imbalances for FDA, and a boost for out-of-state coverage in Medicaid are among Congress’s year end commitments to pediatric and rare disease patients that now seem in doubt.

Clene’s ALS drug CNM-Au8 and UniQure’s gene therapy for Huntington’s disease emerged from US FDA discussions with accelerated approval plans using real-world evidence from compassionate use and natural history data sources.

The incoming EU Health Technology Assessment Regulation will see historical data move “more center stage” for advanced therapies, because directly comparing highly individualized therapies is often unfeasible, an advanced therapies expert says.

The US FDA seeks to better understand and predict insertional mutagenesis in gene therapies like bluebird bio's Skysona, which use integrating viral vectors, but a workshop on integration site analysis highlighted the approach's complexity and limitations.

The European Commission’s proposed pharma legislation overhaul could expand the definition of a gene therapy medicinal product, posing challenges both from a regulatory and public perception perspective.

The company said its financial viability is in jeopardy, along with patient access to Lyfgenia, if US FDA Commissioner Robert Califf does not reverse the denial of a rare pediatric disease priority review voucher.

New US FDA draft guidance attempts to address sponsor confusion about the different types of regulatory meetings under PDUFA, as well as frequently asked questions on nonclinical testing, CMC, pharm/tox and clinical studies.

The move towards greater regulatory collaboration is a positive step for gene therapy developers, Astellas’ gene therapy strategy lead Richard Wilson says – adding, however, that pharma still needed to understand the Asian markets better.

Cell and gene therapy manufacturers based in Europe should speak to local regulators to understand how to demonstrate compliance with EU-level good manufacturing practice guidelines, as each country will apply the rules differently, an expert explains.

Lyfgenia and Zynteglo comprise complex mixtures of transduced cells that represent different active ingredients, the company said in administrative appeals to the FDA. Two lawmakers also raised bipartisan concerns about the agency’s decision on the voucher request for the sickle cell disease treatment.

The UK government has introduced draft legislation that will regulate the manufacturing of innovative medicines such as cell and gene therapies at the point of care. The country’s medicines regulator, the MHRA, says the framework is the “first of its kind in the world.”

Regulators from the US, EU, Japan and UK discuss the merits of regulatory convergence for cell and gene therapies, but say that practical challenges often limit their ability to align on pharmaceutical regulatory processes.

Meeting the regulatory gold standard for drug candidates in ultra-rare diseases can be impractical, a regulatory expert says, but greater collaboration and shared insights from regulatory reviews could help find a viable path forward.