Breaking barriers: strategies for expanding patient access to cell and gene therapies

As of 2023, significant strides have been made in regulatory approvals for cell and gene therapies, with six therapies receiving the green light in the United States (US) and the European Union (EU). The US Food and Drug Administration (FDA) has a robust approval pipeline running to the end of the year, with expected decisions on cell therapies for amyotrophic lateral sclerosis (ALS) and metastatic melanoma, and one gene therapy aimed at addressing sickle cell disease. In November, the first ever CRISPR gene-editing therapy from Vertex and CRISPR Therapeutics for sickle cell disease and beta-thalassaemia was authorised by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

With the possibility of up to nine total CGT approvals this year, this slate of submissions indicates a potentially record-breaking year for the industry. Advanced therapy developers are actively engaged in 2,760 clinical trials, predominantly in North America, setting the stage for a robust future of approvals.

Despite these incredible numbers, we are seeing a decline in regulatory decisions in the EU compared to the US, highlighting the need to better align with international regulatory standards in order to support the broadest possible patient access.

While the industry is no longer riding the record-breaking highs of the bubble, we are seeing a recovery. The industry’s substantial investment, totaling $3bn in the clinical pipeline as of the first quarter of 2023, underscores the significance and potential of this transformative field.

Unlocking the full potential of cell and gene therapies requires a combination of consistent innovation while maintaining investor confidence. As new regulatory approvals are secured, the industry builds confidence and demonstrates their unlimited potential. The successful review of pending submissions by the FDA could significantly alter investor sentiment, positively impacting both the industry and patients. This factor highlights the critical nature of a well-designed clinical trial and closely following FDA guidance during development.  Adhering to these measures early and often while enhancing the quality of clinical trial data will set the product up for success during the regulatory process and can serve as a key driver for attracting investment. By showcasing clinical success with robust safety and efficacy data and by striving to minimise adverse outcomes, confidence in these therapies can be bolstered, potentially drawing more investment into the field.

The CGT sector has grown exponentially, with more than 600 new clinical trials and 1,800 new developers since 2018. The resulting surge in submissions has posed a challenge to the FDA’s regulatory process – without the proper capacity of reviewers, the agency has become backlogged. To mitigate ongoing bottlenecks, additional funding has been allocated to the FDA to recruit more staff and create programmemes to support this wave of technologies. The Office of Therapeutic Products (OTP) was created within the Center for Biologics Evaluation and Research (CBER), an initiative implemented to support the agency’s goal of approving ten to 20 therapies annually by 2025.

The FDA has been working to streamline regulatory processes and provide regular guidance for CGT developers to encourage innovation and support the sector’s growth, while ensuring patient safety. The sector continues to evolve at a rapid pace and the regulatory agency understands these products are complex and have unique needs that must be accommodated. As more products move through the regulatory pipeline, the FDA will continue to publish regular guidance to help companies navigate the regulatory landscape. The OTP director highlights the importance of cell and gene sponsors following the agency’s guidelines as closely as possible, especially in the preclinical stages.  Demonstrating clear evidence of adherence helps move the product and application forward faster, increasing access to these life-saving therapies for patients.

Industry leaders are also working to implement programmemes to support expedited reviews and accelerated pathways. An FDA initiative pilot programmeme, Support for clinical Trials Advancing Rare disease Therapeutics (START), was announced in late September. Three CGT sponsors for rare diseases across two cohorts will be selected to participate in the pilot. Those selected must be running a clinical trial and have an active IND and will be afforded regular advice and ad hoc communication with the FDA to discuss product development and roadblocks. Peter Marks, director of CBER, expressed hope that the insights derived from this pilot programmeme will shed light on ways to streamline the development of life-saving therapies for rare diseases. The aim is to help sponsors produce high-quality data that can substantiate future marketing applications. Recognising the complexity of these products, Marks emphasised the significance of effective communication between sponsors and the FDA to advance products catering to patients with unmet medical needs.

The OTP director also advocates for the implementation of platform designations in the approval of novel CGT treatments. This approach will promote direct communication with sponsors and streamline the review process. Congress has shown support for this by including directives in the omnibus spending bill passed in December 2022, which instructs the FDA to establish a platform designation for drugs or biological products that utilise technologies transferrable to multiple therapies, streamlining development, manufacturing and the review process. Clear communication between sponsors and the agency in combination with regulatory flexibility are crucial for the success and approval of these innovative therapies.

Ensuring affordability and accessibility of these therapies is a complex challenge that demands a collaborative effort between industry stakeholders, federal agencies, healthcare systems and patient advocacy groups. For rare diseases, partnerships are pivotal in expediting therapies to patients. Increasing communication and collaboration across the care ecosystem and initiating these efforts earlier in the development process are critical to helping both sponsors and patients get connected for clinical trials and better understand these small patient populations.

‘Increasing the number of training and development programmes specifically tailored to cell and gene therapy production is imperative’

The efficiency of manufacturing plays a pivotal role in reducing costs and widening the availability of cell and gene therapies. A promising way to refine the manufacturing process across the industry is leveraging platform technologies wherever possible. This concept requires the creation of standardised processes and equipment that can be applied to multiple therapies. It enables the simultaneous progression of multiple products through the manufacturing and approval processes, propelling the entire industry forward. By leveraging these platform technologies, manufacturers can streamline production, cut down on expenses and enhance overall access to these therapies.

A proficient workforce is also fundamental to optimising manufacturing efficiency, and increasing the number of training and development programmes specifically tailored to CGT production is imperative. Such programmes can cultivate a workforce capable of meeting the growing demand for these innovative therapies. Investing in innovative manufacturing technologies while improving process efficiencies increases affordability and ensures that these groundbreaking treatments can reach a broader patient population.

Cell and gene therapies often come with substantial upfront costs for both developers and patients. However, they offer substantial cost-effectiveness in the long term, especially for diseases with limited treatment alternatives. Demonstrating this cost-effectiveness is pivotal to motivate both providers and payers to invest in these therapies. Over the years, industry leaders have assessed several pricing and reimbursement strategies, and it will ultimately require alignment across all stakeholders to determine the best path forward to increase access for patients.

A transition from traditional pricing models to value-based pricing holds transformative potential for the industry. Value-based pricing centres on the outcomes and advantages that patients derive from these therapies rather than merely focusing on the initial cost. This approach aligns incentives and can help foster the adoption of these innovative therapies.  Another innovative strategy involves outcome-based pricing, a model that links the cost of therapies to their real-world results. If the treatment fails to deliver the expected outcomes, costs can be adjusted accordingly. This approach holds sponsors accountable for their products while encouraging the development of therapies that genuinely enhance the lives of patients.

Coverage expansion is another viable pathway that can help ensure that more patients can benefit from these therapies, while negotiating with payers can help secure more equitable reimbursement rates. This, in turn, makes it financially viable for healthcare providers to offer these treatments. As more products move through the regulatory pipeline, addressing pricing models and reimbursement strategies is vital for making these therapies financially viable in the long run. A record-breaking year of approvals is imminent; however, industry success must be defined by the number of patients these novel treatments can reach.

Access to cell and gene therapies is not just a matter of convenience, it is a vital element in enhancing patient outcomes and addressing unmet patient needs. To reach this goal, the industry must focus on refining manufacturing processes, collaborating to overcome regulatory hurdles and working with payers to ensure reimbursements and payment strategies that reflect the value these therapies offer. By investing in technology, training and forward-thinking strategies, we move closer to a future where these groundbreaking therapies are within reach for all who need them.

Anshul Mangal is President of Project Farma and Precision ADVANCE