Complex gene therapies are starting to hit the market but all have faced the same reality: a tepid reception from the healthcare system and a cloudy path to profitability.
CRISPR Therapeutics and Vertex Pharmaceuticals made history with the first approval of a CRISPR-Cas9 gene editing therapy, Casgevy, for sickle cell disease in December 2023. However, the companies' second quarter earnings report in 2024 revealed that no patients had been treated yet.
Patient Preparation and Treatment Timeline
Jen Klarer, managing partner at The Dedham Group, noted that it takes about a year for a patient to go through the necessary preparations to receive the treatment. Vertex reported that 20 patients are "in the funnel" to receive Casgevy, meaning they have signed up and undergone the cell collection process, which can take multiple attempts to gather enough healthy cells. These cells are then sent to CRISPR’s lab for editing to encourage the expression of fetal hemoglobin before being transfused back into the patient.
The timeline for treating patients remains unclear. Myles Minter, a research analyst with William Blair, indicated that investors are concerned about the lack of information on when revenue might start flowing back to the companies. The period from cell collection to infusion can range from one to nine months.
Reimbursement Challenges and Access
A major challenge for Casgevy is securing insurance coverage, given its list price of $2.2 million. While the therapy offers a one-time curative intent, potentially avoiding a lifetime of healthcare costs associated with sickle cell disease, the healthcare system is not structured to easily accommodate such high upfront costs.
Klarer explained that patients with commercial payers are likely to be the first to access Casgevy, with coverage decisions typically made within three to six months of approval. Medicaid and Medicare patients, however, may face longer delays, potentially up to a year, before coverage is approved. The Centers for Medicare and Medicaid Services (CMS) has introduced the Cell and Gene Therapy (CGT) Access Model to address these issues, tying payments to outcomes to facilitate state coverage of expensive treatments, initially focusing on sickle cell disease.
Fertility Treatment Coverage
Another significant hurdle is the coverage of fertility treatments, which patients may need alongside Casgevy due to the therapy's potential impact on fertility. Both Vertex and bluebird bio have been vocal about the challenges in obtaining coverage for fertility preservation. Vertex even filed a class action lawsuit against the HHS' Officer of Inspector General over the inability to offer fertility support programs to federally insured patients without facing penalties.
Market Dynamics and Future Prospects
While smaller companies like CRISPR and bluebird are pioneering complex gene therapies, larger pharmaceutical companies such as Eli Lilly and Pfizer, with gene therapies in their pipelines, may be better positioned to navigate the initial commercial challenges. CRISPR benefits from its partnership with Vertex, which has a well-established cystic fibrosis franchise. However, the profits are split 60/40, with Vertex handling commercialization.
Minter remains confident that Casgevy can eventually generate $3 billion or more in annualized revenue, with William Blair estimating peak sales at $3.6 billion. He emphasized that Casgevy's success is more significant as the first approved CRISPR gene editing drug launch than for its immediate impact on Vertex's profit and loss statement.
Klarer stressed the importance of gathering meaningful clinical data and streamlining manufacturing processes to ensure scalability for future gene therapies.
