The Battle For Sickle Cell

I wrote here a couple of years ago about the problems being experienced by Bluebird Bio, pioneers in commercializing human gene therapies. The summary is that despite getting three of these through FDA approval, the company was in desperate conditions and heading for bankruptcy, because none of them were being taken up by potential patients in enough numbers to justify the costs.

They went public back in 2013, and at one point their stock was nearly $50/share. But those difficulties sank them, and last year they were acquired by a private equity group at what must have been well under a dollar per share. They’ve been renamed back to their original “Genetix” in an attempt to leave the bad times behind.

Have they? Stat has an interesting interview with their current CEO, David Meek, who has adopted a tone for it that is well-characterized as “swaggering”. He says that by 2030 they’ll be treating 1,000 sickle cell patients per year, and that the company is already profitable. Doubt is admissible about both those claims. Last year they say that they treated somewhere over 100 patients (and if it was as many as 150, believe me,  they’d have said so). There are a lot of challenges in raising that number by a factor of ten - manufacturing (which is absolutely no joke in this area), finding suitable patients, collecting their cells, expanding hospital capacity for the labor-intensive treatment process, and more. These are all pretty chewy, and solving them simultaneously would be a remarkable achievement. I think that Meek is engaging in the sort of braggadocio that makes you wonder how much substance  is really behind it, and I think that he has only his own statements to blame for such skepticism. We’ll revisit eventually and see who’s wrong.

To get another vantage point, take a look at the other sickle-cell gene therapy on the market, Vertex’s Casgevy. They say that they treated 64 people last year, but apparently 30 of those were in the fourth quarter of the year. Whether that indicates an upsurge or not is up for debate. And it’s also an open question how many patients Vertex needs to be treating for Casgevy to be profitable at all. Some economies of scale will have to kick in, because even at $2.2 million per treatment it’s unlikely that they’re making much profit so far (if indeed they’re making any at all). My guess is that they aren’t.

Add to this the hoofbeats coming up behind both companies from Beam Therapeutics, with their own sickle cell therapy “Risto-cel”. This is a stem-cell transplant therapy where a patient’s CD34+ cells have been base-edited to interfere with BCL11A activity, which should allow fetal hemoglobin (non-sickling!) to be produced again and take over the oxygen-carrying duties. A lot of people have worked on BCL11A therapy ideas over the years, but this a direct shot on that mechanism. Beam is hoping to get approval next year, and their version of gene therapy could prove to be easier to realize than either Genetix’s or Vertex’s. No one knows yet, but you’d want to be ready for that possibility if you’re in the business.

So the whole curing-sickle-cell-through-gene-therapy story is a long way from being written. But it’s for sure that it has not gone like some of its participants have wanted it to. There are patients out there who have had their lives changed, but there are plenty more who could potentially be in that category. Will they ever get the opportunity to try?