Weekly reads: Verve Therapeutics, Casgevy UK OK, GDNF, MYC

Some folks can view data from early, small clinical trials too skeptically or overly enthusiastically, and maybe that’s going on with some preliminary results from Verve Therapeutics. Good news? Bad news? I’m going to start with two articles about the same news that have very different vibes. What do I think?

On the whole, I feel like it’s good news, but it’s early trial news. So some caution and balance are needed.

The Verve investigational therapy had big positive effects on some participants’ LDL cholesterol. While two participants died, the group had serious heart disease to start with and it’s unclear if the deaths were treatment-related. This was an N=10 trial.

For context, statins work incredibly well to lower LDL. Some people do have side effects from statins though. Others don’t want to take a pill every day or forget. This LDL-lowering gene therapy, if it is ultimately successfully approved as safe and effective, might be a one-and-done approach, which has appeal.

2 opposite vibes on Verve Therapeutics gene editing for  cholesterol

• First trial of ‘base editing’ in humans lowers cholesterol — but raises safety concerns, Nature.
• New Gene Editing Treatment Cuts Dangerous Cholesterol in Small Study, NYT. Subtitle: “The trial involved only 10 patients, but it suggests cholesterol can be permanently reduced with a single treatment for patients at risk of heart disease.”

These two article titles feel very different, right? I found yet another one more focused on the deaths.

Where do you land on Verve’s data?

Gene therapy field moves forward

Overall, I feel optimistic about clinical use of gene editing as a field in the long run including the exciting sickle cell work. However, it’s not going to be as simple or quick as some seem to think. Many trials will fail. There are likely to be some serious side effects in certain cases. Even some investigational therapy-related deaths. However, on the whole, with what will be hundreds of trials, in the end, I predict that many more lives will be improved and saved.

You could say the same thing about the hundreds of clinical trials on stem cells and other cell therapies. We’ve already seen how hard the trial process can be there.

Here’s another new gene therapy item: In analysis of gene therapy deaths, Astellas points to underlying liver issues, Fierce Biotech.

Even for the successes, cost will be a big issue, potentially around a million or even millions a pop.

Casgevy gets UK OK for sickle cell disease & β-thalassaemia

Speaking of price tags, the cost of the first approved gene editing therapy will likely be around $2 million USD per treatment.

Yes, there is now an approved CRISPR therapy as of this week. The UK just okayed Casgevy for sickle cell disease & β-thalassaemia. 

Vertex and CRISPR Therapeutics make Casgevy. I just highlighted Vertex this week as a cell therapy company that is doing well. In my yearly predictions for the stem cell and regenerative medicine field for 2023, I also predicted a good year for CRISPR Therapeutics.

Other recommended reads

• Stem cell–like reprogramming is required for leukemia-initiating activity in B-ALL, JEM.
• Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration, Stem Cells.
• A Germline Point Mutation in the MYC-FBW7 Phosphodegron Initiates Hematopoietic Malignancies., bioRxiv. This preprint is from my old postdoc mentor Bob Eisenman at The Hutch. I’ve also co-authored work with a couple of the other authors from Irvine Berstein’s lab. Cool work on MYC. When I read a paper like this I wish my own lab was doing more on MYC still. We’ve been focusing relatively more on histone H3.3.
• Ethical, legal and social aspects of human cerebral organoids and their governance in Germany, the United Kingdom and the United States, Frontiers in Cell and Developmental Biology.