The gene editing therapy Casgevy is gaining momentum in the marketplace, with CRISPR Therapeutics and partner Vertex Pharmaceuticals reporting an expanding treatment network and early revenue growth. Simultaneously, CRISPR's pipeline is advancing with promising data from its liver-targeting gene therapy program, potentially signaling a broader application of the company's gene editing technology.
Vertex reported this week that 65 treatment centers for Casgevy have been activated globally, approaching their target of 75 centers. This infrastructure development is critical for the gene therapy, which received FDA approval in December 2023 for sickle cell disease and beta-thalassemia but faced a slow commercial launch.
The companies reported $14.2 million in Casgevy revenue for the first quarter of 2024, representing a 4% increase that analysts at William Blair interpreted as a positive sign that "the ramp in patient starts is beginning to convert to a ramp in cell infusions."
Patient Adoption Gradually Building
Patient adoption metrics show early progress in the treatment pipeline. According to Stuart Arbuckle, Vertex's Chief Operating Officer, approximately 90 patients have undergone the initial cell collection process necessary for the gene therapy, while more than twice that number have been referred to begin treatment. To date, eight patients have completed the full treatment course.
"Casgevy truly does have the potential to be a multibillion-dollar product for Vertex," Arbuckle stated during the company's first quarter earnings call. "It's been inspiring to hear that Casgevy patients now feel able to live their lives in ways they never have before, whether that means having the energy to play with their kids, taking up snowboarding without fear that the cold might bring on a pain crisis, or investing in their education and careers given expectations now for a longer and healthier life."
The progress comes against a challenging backdrop for gene therapies broadly. Competitor bluebird bio, once a promising player in the space, recently sold to private equity for just $30 million after failing to achieve profitability. Gene therapies face significant hurdles including high costs, complex administration requirements, and the need for specialized treatment centers.
Expanding the Gene Editing Portfolio
While Vertex leads commercialization efforts for Casgevy, CRISPR Therapeutics is advancing its broader pipeline. The company recently reported encouraging Phase I data for CTX310, an in vivo liver-editing therapy targeting the ANGPTL3 gene, which regulates lipoprotein (LDL) and triglyceride (TG) levels.
In the small first-in-human trial involving 10 patients with elevated lipid levels, a single dose of CTX310 successfully decreased ANGPTL3 gene expression, resulting in reduced LDL and triglyceride levels. Notably, one patient with severe hypertriglyceridemia experienced an 82% reduction in triglycerides, while another with heterozygous familial hypercholesterolemia showed an 81% reduction in LDL-C.
William Blair analysts noted that the data "looks competitive" with reductions seen in other therapies, including Arrowhead Therapeutics' ARO-ANG3 and Regeneron's approved therapy Evkeeza. Importantly, CTX310 was well-tolerated with no severe adverse events reported and no elevation in liver enzymes across all dose levels.
Future Pipeline Developments
CRISPR Therapeutics characterized the CTX310 results as a "significant milestone" for its proprietary lipid nanoparticle (LNP) delivery technology for gene editing in the liver. The company plans to present more comprehensive data from the Phase I trial at an upcoming medical meeting later this year.
The pipeline continues to expand with CTX320 for cardiovascular disease, which is expected to yield Phase I results in the second quarter. Analysts at William Blair suggested that the safety profile demonstrated by CTX310 "de-risks the upcoming readout from CTX320," noting that CRISPR is "the only company with an in vivo gene-editing candidate targeting Lp(a) in the clinic."
Additional programs in development include CTX340 for refractory hypertension and CTX450 for acute hepatic porphyrias, both in preclinical stages. In oncology, CRISPR anticipates a readout for a Phase I trial of CTX131 in solid tumors and blood cancers later this year. The company also expects to provide an update on CTX211, its regenerative medicine approach for diabetes, before the end of 2025.
As CRISPR Therapeutics continues to demonstrate the versatility of its gene editing platform across multiple therapeutic areas, the gradual commercial progress of Casgevy provides an important test case for the viability of gene therapies in the marketplace. The next 12-18 months will be critical in determining whether the promise of these transformative treatments can overcome the practical challenges of bringing them to patients at scale.
