The State Of CRISPR Clinical Trials And Their Future Potentials

CRISPR, short for “Clustered Regularly Interspaced Short Palindromic Repeats” - and more specifically CRISPR–Cas9 - relates to a gene-editing method that gained popularity in the past decade; and not for trivial reasons. Being the most efficient and accurate method to edit a cell’s genome, CRISPR holds potentials that range from treating conditions such as HIV to finding new drug targets.

While such potentials are real and are being actively investigated, you might be curious about more practical examples of CRISPR applications. By taking the US Clinical Trials registry as an example, we consider listed clinical trials that involve CRISPR technology as of late November 2023. Such an undertaking can provide a better appreciation of the state of CRISPR potential, as well as practical use cases that we can expect in the coming years.

Clinical trials involving CRISPR?

For this analysis, we looked at the CRISPR entries on ClinicalTrials.gov, which is an online database of clinical research studies and shares information about their results. This database is maintained by the United States National Library of Medicine at the National Institutes of Health and holds registrations from over 444,000 trials from 221 countries. At the time of writing, 51 CRISPR/Cas9-related studies were identified on ClinicalTrials.gov and they could roughly be categorised as completed, ongoing, or terminated based on their statuses.

1. Completed CRISPR clinical trials

Considering that clinical trials can take over 10 years to complete, it is no surprise to see that from the database, the minority of the entries (only 6) are listed as complete. Most of them studied the safety and efficacy of potential new treatments involving CRISPR, whether it was modified cells or a new product targeting viral cells.?

For example, one completed Phase I clinical trial involved CRISPR-edited T cells in patients with advanced non-small-cell lung cancer; with endpoints being the safety, feasibility and efficacy of these modified T cells. The results indicated that the clinical application of CRISPR gene-edited T cells is generally safe and feasible; while the therapeutic efficacy could be improved.

Notably, half of the completed trials investigated interventions for advanced cancer types. The remaining involved either diabetes, viral eye infection or Kabuki syndrome (a rare genetic disorder).

2. Ongoing CRISPR clinical trials

The vast majority of the CRISPR clinical trials on the database, or 30 of them, are ongoing, whether they are actively recruiting or not. They are mostly investigating the safety of CRISPR-based therapies either for cancer treatment ranging from renal cell carcinoma to lymphomas or genetic disorders such as thalassemia and sickle cell disease.

To illustrate one of the areas of focus, one of the listed trials is following up with patients who received CRISPR-modified hematopoietic stem infusion for either β-thalassemia or severe sickle cell disease. The aim is to determine the long-term safety and efficacy of the treatment. In particular, the researchers are interested in determining the occurrence of new or worsening conditions, as well as severe adverse events up to 15 years after the treatment.

As for the remaining trials, one is studying the effects of CRISPR-modified pancreatic cells for Type 1 diabetic patients; and another trial is investigating a new CRISPR-based drug for HIV treatment.

3. Terminated CRISPR clinical trials?

15 of the entries are either labeled as terminated, suspended, withdrawn or have an unknown status. Nearly all of them investigated the treatment of cancers, but their outcomes will likely remain unknown considering the statuses of the trials.?

As there are some overlaps with conditions of focus in ongoing trials, the less positive outcomes of terminated trials do not mean that other therapies aren’t possible. It means the approach of a certain trial did not pan out as initially planned, which could be due to several causes from lack of funding to poor recruitment of participants.?

What to expect from CRISPR in healthcare

As the database indicates, CRISPR’s potential to devise new treatments is actively being investigated by researchers. In particular, we can expect a more significant impact of CRISPR in the potential treatment of cancers and genetic disorders, as the majority of trials currently have such a focus. Interest in such conditions is understandable considering that there are over 18 million cancer cases worldwide and 2–5% of all live births are affected by hereditary diseases.

However, CRISPR-based treatments for less prevalent conditions are also gaining interest. For instance, the database lists a completed observational study around gene therapy for Kabuki syndrome, a rare genetic condition that affects children at an estimated frequency of 1:32,000 to 1:86,000. This indicates that the efficacy of CRISPR-based therapies could be assessed for a wider pool of conditions in the coming years.?

It should be noted that even if a trial has been completed, the proposed therapy might undergo further rounds of assessments to minimize identified risks and side effects. Furthermore, upon completion of clinical trials, the treatment will need to get approval from relevant health authorities. This means more time before seeing marketable solutions for everyday patients.

But we might be on the cusp of having CRISPR-based treatments become more widely available. The technology has been refined, with the potential to be more specific and applied for common diseases such as high cholesterol. In late November 2023, the world’s first CRISPR therapy was approved by the UK’s regulator. Named Casgevy, the treatment is aimed at sickle cell disease and transfusion-dependent β-thalassemia.?

This is promising progress considering that CRISPR–Cas9 gene editing therapy was introduced 11 years ago. More might follow suit soon, enabling patients to benefit from treatments for otherwise incurable conditions.?