Three opportunities and three challenges in the cell and gene therapy market

1. Approvals 
2022 saw the approval of three new gene therapies to treat rare diseases and a fourth approved to treat bladder cancer. Five therapies previously approved in either the United States or the European Union were authorized for treatment in a new location or to serve patients with a different indication.¹ 

2023 may bring the exciting news of an approved therapy to treat sickle cell disease. The first CRISPR- based autologous gene therapy, it was validated in the European Union in January, and edits patients’ own hematopoietic stem and progenitor cells that are re-infused.¹ 

Experts predict up to 13 new CGT could be approved in the United States and/or Europe by the end of this year.² In 2019, the FDA predicted it would approve over 10 new CGTs by 2025³—and that prediction seems well within reach. 

2. Regulatory  
Flexibility around regulatory frameworks will encourage innovation. Efforts to modernize the Food and Drug Administration’s Center for Biologics Evaluation and Research may have a positive impact. The FDA’s Office of Tissues and Advanced Therapies (OTAT) — the office that principally manages the approvals for cell and gene therapies —become the “Office of Therapeutic Products” (OTP) in 2023⁴ and is considered a “super office,” meaning staff will be better structured to address the growth in cell and gene therapies. 

A vital program to help the FDA gear up for the predicted wave of cell and gene therapies is the Prescription Drug User Fee Act (PDUFA). Congress approved the seventh iteration of the act which permits the FDA to collect fees from biopharma companies that are used to fund review processes for new drugs.⁵ 

In the European Union, the European Commission’s efforts to review and update pharmaceutical legislation will create a future-proof regulatory system. The European Medicines Agency continues to serve as a leader in the regulatory space, and the E.U. had a great heritage as it approved the first-ever gene therapy. 

3. Rise of allogeneic therapies 
Allogeneic therapies, those made in large batches from unrelated donor tissues (such as bone marrow), are having a moment. Atara’s allogeneic T-cell therapy for the rare cancer Epstein-Barr virus positive post-transplant lymphoproliferative disease was approved in the European Union in December 2022 and approval in the United States is predicted for 2023.⁶ 

Allogeneic cell therapies offer certain advantages over autologous products. These include the potential to accelerate time to treatment and the potential to reduce the costs of goods and broaden access globally. 

With these therapies, integration with cellular orchestration systems is essential, to keep the supply chain moving smoothly, as therapy developers may prefer batches of fresh cells. 

A global good manufacturing practices (GMP) depot network for storage is also crucial for autologous therapies. Under good manufacturing practices, biopharma companies can ship cells from a manufacturing site before conducting all quality tests. The product must be stored under quarantine in a GMP depot close to the hospital where the patient will receive treatment. When those quality results are released, the therapy is already near its destination and can be delivered immediately. 

1. Affordability  
In the U.S. market, the potential approval of therapies for sickle cell disease will shed light on whether the health care system, and especially Medicaid, is equipped to provide access to treatment. This underlines a growing concern that existing payment systems aren’t set up to handle a potential influx of approved CGTs.  The proposed Medicaid VBPs for Patients bill seeks to remove barriers to using value-based purchasing arrangements, including outcomes-based agreements, in  Medicaid.⁷ 

For its part Europe is working to reduce market access barriers, but affordability is a challenge in that market as well. The substantial upfront costs of a single treatment—millions of euros—are difficult for the local health care systems to bear, especially without guarantees treatment will be successful.  

As more therapies hit the market, the demand to shoulder these costs will only grow. Outcomes based agreements that spread the risk between payers and therapy developers, could grow in popularity. These innovative payment agreements could benefit patients not only in Europe, but also in the United States, where payers and biopharma often disagree with the approaches offered by biopharma. 

2. Lack of standardization 
Cell and gene therapies are typically administered in a select few centers of excellence, each with its own processes. That is compounded by the fact that each biopharma company has its own standards and procedures, too. 

A lack of standardization is particularly troublesome with autologous therapies, those that use the patient’s own cells or tissues to build the therapy. In those cases, since the patient is part of the supply chain, efficiency and patient support services need to be top of mind.  

3. Clinical trials 
Therapy developers in the clinical stage are finding it difficult to access the patients needed to complete clinical trials, especially with rare diseases.  Specifically in the European Union, data privacy laws require consent for each time patient data is used and can add time to trials.8 

On their end, patients are potentially missing out on the benefits of experimental therapies delivered in clinical trials. According to the Alliance for Regenerative Medicine, the pipeline for early phase clinical trials in Europe is shrinking.⁹ 

Across both American and European markets, cell and gene therapies may present limited clinical data, mostly because of their indications for rare diseases with few (if any) comparative treatments.   

From the payers’ perspective, this leads to uncertainty in determining the benefits of the new CGT when compared against existing treatments.  The trials for these products are often short and based on surrogate endpoints; while the treatment effects are intended to be lifelong.