Traditional gene therapy has seen numerous challenges during its decades of development, but scientists seem to have finally figured out how to get the treatment to work with regulatory approvals for Novartis' (NYSE:NVS) Zolgensma and bluebird bio's (NASDAQ:BLUE) Zynteglo this year. The process involves inserting genes into diseased cells to express missing or mutated proteins.
Storming onto the scene over the past few years, CRISPR/Cas9, championed by CRISPR Therapeutics (NASDAQ:CRSP), Editas Medicine (NASDAQ:EDIT) and Intellia Therapeutics (NASDAQ:NTLA), offered hope for more precise gene editing. At the very least, the process can insert the gene into a precise location in the genome. More impressive -- and something that traditional gene therapy can't readily do -- CRISPR/Cas9 offers the possibility of deleting problematic genes or making specific changes to mutated genes to restore their functions.
CRISPR/Cas9 appeared to be working well in preclinical models, and last week, investors got a first look at how the therapy is working in humans with CRISPR Therapeutics and its development Vertex Pharmaceuticals (NASDAQ:VRTX) announcing results for the first two patients treated with CTX001.
One patient with a blood disorder called transfusion-dependent beta thalassemia (TDT) required 16.5 transfusions per year over the two years before being treated with CTX001, but nine months after treatment, the patient was transfusion independent with high expression of fetal hemoglobin, the gene inserted into the patients' cells.
The other patient had sickle cell disease (SCD) with an average of seven vaso-occlusive crises (VOCs) per year over the two years before the study started. Four months after being treated with CTX001, the patient was free of VOCs, which are caused by sickle-shaped red blood cells that block blood vessels. Like the beta thalassemia patient, the SCD patient had expression of fetal hemoglobin.
The results from the first two patients look comparable to Bluebird's Zynteglo, which also treats TDT and SCD by increasing hemoglobin levels. But this was data from just two patients, and investors should still have plenty of questions as we get additional data:
Consistency: One patient in each disease doesn't say much about how well the treatment works in the average patient. What will the efficacy look like after the treatment of a few dozen patients?
Durability: Gene editing and gene therapy are designed to be cures. Do both last forever?
Manufacturing: Bluebird had to adjust its manufacturing procedure to increase expression to treat patients requiring higher expression. Will the initial CRISPR/Cas9 manufacturing procedure work for all patients?
In vivo/ex vivo: That's Latin for in or outside of a living thing -- in this case a human being. CTX001 and Zynteglo are ex vivo treatments because cells are taken from the patient, manipulated to express the gene of interest, and put back into the patient. Novartis has shown that gene therapy can work in vivo with Zolgensma delivered via an injection of a viral vector. Can CRISPR/Cas9 work in vivo in humans? Editas Medicine hopes so, but the company still hasn't advanced a treatment into the clinic.
Last week's data release offers plenty of hope for investors in CRISPR/Cas9 and traditional gene therapy companies should certainly be looking in the rearview mirror at the technology coming up from behind, but it's still way too early to pick a winner between traditional gene therapy and CRISPR/Cas9.
The right answer for investors in biotech companies might end up being to buy both. The upside potential for curing diseases may end up outweighing the downside if one technology doesn't end up working out.