CRISPR in 2024 and Beyond

Table of Contents

When the paper by Jinek et al. detailing the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technique was published in 2012, it opened unprecedented possibilities in treating genetic diseases and suggested a future where genetic disorders could be definitively cured (1). Just twelve years later, we are beginning to experience this as a reality. At the end of 2023, we saw the first FDA-approved treatment using CRISPR hit the market from Vertex Pharmaceuticals for sickle cell disease and transfusion-dependent beta thalassemia.

Looking ahead to the rest of 2024 and beyond, the momentum in gene editing from CRISPR technology does not show signs of slowing.

CRISPR: Looking Beyond

Diabetes: Can CRISPR Restore Insulin Production?

There is a Phase I/II trial in progress to treat type 1 diabetes. Developed by CRISPR Therapeutics, CTX211 aims to treat the disease by transplanting healthy beta cells derived from stem cells into patients.

By utilizing CRISPR-Cas9 technology, CTX211 enhances the fitness of donor cells and allows them to evade the host immune system, potentially providing a long-term solution for patients without the need for chronic immunosuppression (2).

This therapy would represent a paradigm shift in diabetes management, offering the possibility of restored insulin production and improved quality of life for patients.

Infectious Disease: CRISPR in HIV and Hep B

Infectious diseases also stand to benefit from CRISPR-based interventions, with ongoing trials targeting conditions like HIV and hepatitis B.

Excision Biotherapeutics' EBT-101 aims to cut the HIV virus from the genome of human cells using CRISPR-Cas9, offering the potential for a functional cure for HIV (2).

Similarly, Tune Therapeutics' TUNE-401 utilizes CRISPR epigenetic editing to silence all forms of the hepatitis B virus in the human liver, presenting a promising avenue for treating this chronic infection (2).

Commercialization and Investment

Challenges

• Small Markets: Initially, the commercialization of CRISPR-based therapies will be the small market for therapies targeting rare genetic disorders. While these barriers may disappear as therapies expand beyond rare disorders, limited patient populations make it difficult to enroll enough participants for clinical trials.
  

• Scalability: The personalized nature of these treatments can hinder scalability. Much like CAR-T therapies, CRISPR-based therapies may require autologous processing and handling, which complicates manufacturing and distribution. This results in higher operational costs and logistical barriers, similar to what has been observed with CAR-T therapies such as Kymriah and Yescarta. The ability to develop an allogeneic approach will enable scaling CRISPR.
  

• Licensing and Royalties: Companies will have to license the CRISPR technology and pay royalties, creating additional costs.

CRISPR-based therapies may require autologous processing and handling, which complicates manufacturing and distribution. The ability to develop an allogeneic approach will enable scaling CRISPR.

Benefits

• Investor Appeal: CRISPR-based therapies hold considerable promise, offering one-time, potentially curative treatments that can command premium prices and attract significant investor interest.
  

• Orphan Drug Status: CRISPR therapies currently target rare diseases, which can qualify for orphan drug status with its associated exclusivity and financial benefits.

Access, Pricing, and Reimbursement Challenges

The high cost of CRISPR therapies will present significant pricing and reimbursement challenges similar to those faced by other gene therapies (3, 4). Innovative payment models are needed to address these disparities and ensure equitable access (5):

• Amortization, for instance, could spread the cost of therapies over time, easing the immediate financial burden on payers.
  

• Risk spreading models involve pooling resources or purchasing reinsurance to cover high-cost claims.
  

• Performance-based payment models offer alternative solutions by adjusting costs based on the therapy’s effectiveness.
  

• However, implementing amortization or performance-based-payment models in the U.S. multi-payer system poses significant challenges due to the need for standardization across various insurance entities, as each entity would need to agree on the terms and structure of the payments.

• The risk-sharing model would require collaboration between payors; achieving consensus on the terms of risk sharing agreements would be challenging, and the administrative overhead associated with coordinating and managing pooled resources or reinsurance policies could further complicate implementation.

The View from the Crow’s Nest

The advent of CRISPR-based therapeutics has been more than a decade in the making, and with Casgevy’s recent approval, we are beginning to see what a world with these treatments looks like. While CRISPR Therapeutics and others continue to race towards treatments for other indications, some challenges will need to be addressed. High development costs and the prospect of one-and-done treatment contribute to eye-watering therapy prices, which have insurers concerned and could limit utilization.

We’ll be monitoring the evolution of this promising new technology and are hopeful that some of the challenges we’ve outlined can be addressed.

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If you are interested in learning more, get in touch at strategy@spinnakerLS.com. 

Spinnaker offers true partnership and comprehensive guidance to help leaders navigate the complexities of the Life Sciences industry and chart a path to success. From early-stage market assessment through commercial execution and ongoing lifecycle management, we deliver tailored solutions to ensure optimized practicable results.

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Sources:  

1.      A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity (https://pubmed.ncbi.nlm.nih.gov/22745249/)

2.      CRISPR Clinical Trials to Follow in 2024 and Beyond (https://www.synthego.com/blog/crispr-clinical-trials-2024)

3.      A look at how payer executives are thinking about novel, high-cost therapeutics (https://www.fiercehealthcare.com/payers/look-how-payer-executives-are-thinking-about-novel-high-cost-therapeutics)

4.      The gene-therapy revolution risks stalling if we don’t talk about drug pricing (https://www.nature.com/articles/d41586-023-01389-z)

5.      Confronting high costs and clinical uncertainty: Innovative payment models for gene therapies (https://pubmed.ncbi.nlm.nih.gov/37931198/)