Friday was a monumental day for those living with sickle cell and those pursuing cell and gene therapy solutions for various diseases. Earlier this year, December 8th was announced as the date for the FDA’s official decision on Casgevy for the treatment of sickle cell disease (SCD) — a decision that the world of healthcare, including HDMZ, awaited with bated breath. And now, following on the heels of a November approval in the UK, the day has arrived: For the first time, FDA regulators have approved a medicine based on CRISPR gene-editing technology.
SCD is a genetic blood disorder involving a mutated form of hemoglobin that causes red blood cells to form a sickle-like shape. These abnormal cells are unable to carry oxygen, and result in blockages that can cause pain and significant disruptions to everyday life. Casgevy (also known as exa-cel) directly edits the DNA in a patient’s blood stem cells, using CRISPR-Cas9 technology. This enables the cells to produce fetal hemoglobin, a functional form of hemoglobin that is normally not produced after birth.
In all, it took just under a decade for the development and approval of Casgevy, a joint collaboration between Vertex Pharmaceuticals and CRISPR Therapeutics: Development began in 2015, while clinical trials involving human patients began in 2019. Though ten years is not typically considered a particularly short period of time, by the standards of drug discovery, this was an incredibly swift timeline. The speed becomes even more remarkable when considering the fact that seminal studies on the use of CRISPR-cas9 on human or animal cells were published in 2013, only two years prior to the start of work on Casgevy.
Watching history in the making
When the FDA convened an advisory committee to debate the therapy’s approval on October 31, it was akin to watching history in the making, with insights from thought leaders in the field, personal accounts from patients with SCD, perspectives from representatives of Vertex, and critiques on the data from regulators.
A key point of discussion was concern about the long-term effects of the therapy. Some felt that the data was insufficient, with not enough participants in the study. Additionally, there was some criticism of the depth of the initial study’s investigation of off-target effects in a relevant population. However, the ultimate sentiment of the committee was that it should “be careful to not let the perfect be the enemy of the good.” In other words, the search for perfection should not be an impediment to FDA approval and, ultimately, the therapy’s overall benefits — particularly when there has been a large unmet need in treating sickle cell disease.
Although Casgevy has been approved, Vertex will continue to conduct long-term studies to ensure the ongoing safety of the treatment, and to address the above concerns. These will consist of two 15-year studies: one registry-based and one as follow-up for an ongoing trial.
A new era in medicine
Ultimately, the approval of Casgevy represents a future in which we can think about not just treating the symptoms of genetic diseases, but also resolving them entirely. With just one treatment, patients can be cured of diseases that were previously considered incurable. HDMZ has been proud to partner with giants in the field of CRISPR and gene editing, and to contribute to the enormous strides being made to change the course of human medicine.