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Matthew Pech: The failure of ex vivo gene therapy for sickle cell and the role of the TPP in the drug development process

Matthew Pech/LinkedIn

Dec 31, 2024, 03:37

Matthew Pech: The failure of ex vivo gene therapy for sickle cell and the role of the TPP in the drug development process

Matthew Pech, Cofounder and VP of Newco, shared a post on LinkedIn:

“The failure of ex vivo gene therapy for sickle cell and the role of the TPP in the drug development process.

By failure, I mean how a treatment that is highly efficacious and seemingly the poster child for the promise of gene therapy has had such limited patient adoption.

~60 patients in total got dosed with casgevy in 2024…

While Vertex is still ramping up, I’m pessimistic that this ends up being the ‘multi $B opportunity’ vertex highlighted in their investor updates; I’d guess a 1-2000 patients max ever get this drug – in other words, the uptake of gene-edited auto-BMTs to cure SCD ends up being about as (un)popular as the approach it replaces (allo BMTs).

With these numbers you can see why Editas just pulled the plug on its analogous program…

What went wrong, and were these failures foreseeable?

Developing drugs is the process of creating safe and efficacious therapies, that are convenient and tolerable, and that society wants to pay for. Target product profiles (TPPs) are essentially the quantitative version of that previous statement, in which you lay out the series of attributes you think the drug will need to meet to rationalize further development.

In casgevy, I see a failure of the TPP process – people not stepping in early in the development process to say ‘Look, for SCD, ex vivo gene therapy with myeloablative conditioning isn’t good enough.

Even if the therapy works, we won’t be able to convince (young) patients to put their life on hold for 6-12months as they undergo a lengthy and difficult mobilization and conditioning treatment, all while risking going infertile, while navigating huge price tag for both the therapy and all the time in the hospital, all while knowing better therapies may be coming down the pipeline in the next 5-10years.’ “