Watch Out bluebird bio, CRISPR Is on Your Heels

For many years bluebird bio (BLUE 1.78%) has been in the lead for developing a potential cure for beta thalassemia and sickle cell disease. But CRISPR Therapeutics (CRSP 1.35%) and its partner Vertex Pharmaceuticals (VRTX 1.25%) are looking to compete with a potential cure of their own. In this video from Motley Fool Live recorded on Dec. 7, Corinne Cardina, bureau chief of healthcare and cannabis, and Fool.com Contributor Brian Orelli discuss the differences between the two treatments and the data updates from the American Society of Hematology (ASH) annual meeting.

Corinne Cardina: So we got some exciting updates at ASH, particularly in the battle for a cure for two genetic blood diseases. The first one is sickle cell disease and the second, you mentioned, beta thalassemia. CRISPR Therapeutics and Vertex Pharmaceuticals, they have a candidate called CTX001. They gave us an update, and then we also got an update from bluebird bio, their candidate is called beti-cel. Brian, what can you tell us about what these two treatments are and where they are in development?

Brian Orelli: Bluebird's beti-cel is definitely in the lead. That's the generic name. It used to go by the codename LentiGlobin, so if you were trying to figure out what that beti-cel is, it's the same thing as LentiGlobin. Then the beti-cel is short for a really long name that starts in beti and ends in cel. We'll just call it beti-cel because that's what the company is referring to it as. That's already approved in the EU under another brand name -- because we definitely need another brand name -- called Zynteglo for patients with transfusion-dependent beta thalassemia who don't have the worst genotype. Beta thalassemia comes in different genotypes. The worst one wasn't covered under that approval. But they are working on getting it approved through that one as well. They're looking for an FDA marketing application for beta thalassemia in the US in mid-2021.

Then the sickle cell application was just recently delayed, and so it's not going to be able to be for application until late 2022. The FDA had some issues with the commercial stage manufacturing. I think we talked last week about a vaccine maker that was delaying their phase 3. They had their commercial manufacturing setup, so bluebird didn't do that, and so now they have to approve that their old manufacturing setup and their commercial manufacturing set up are equivalent.

Then CRISPR and Vertex's drug is still in phase 1 development and they are running clinical trials for both of the diseases separately.

Cardina: Both of these drugs edit the DNA of patients' cells, but do they work in the same way? Are these equivalent treatments?

Orelli: Yeah, no, they definitely work. They're definitely different. Bluebird is sort of a traditional gene therapy, so they are basically just adding back in hemoglobin, that's the problem in both beta thalassemia and in sickle cell diseases that patients' red blood cells don't have enough hemoglobin. In sickle cell, they sickle and then they bind up and they cause problems in the vascular system. Then for beta thalassemia, they're not carrying enough hemoglobin. Bluebird's puts hemoglobin back in in traditional gene-therapy way.

CRISPR, obviously, used its CRISPR-Cas9, which edit DNA so that's different. But then what they are doing is they're disrupting a gene called BCL11A. What BCL11A does is when you're born, it turns off fetal hemoglobin and then that results in your, they call it adult hemoglobin, comes on, and so by deleting, making the mutation in BCL11A, it turns off BCL11A and that results in the patients expressing fetal hemoglobin, which appears to be working to compensate for the lack of the adult hemoglobin in beta thalassemia patients.

They are both ex vivo, so that means you take the cells out of the patient, you manipulate them in a laboratory and then put them back in versus in vivo, where you have to try to get the gene editing to the right cells within the body, which is obviously harder.

Cardina: Great. What data did each company release at ASH? What's the top-line news here?

Orelli: The CRISPR data is obviously, because it's earlier stage, it's a lot more important. They have seven patients that have been treated with beta-thalassemia, they were treated 3-18 months ago, and all of those patients don't need new transfusions of red blood cells. That's basically the marker whether you're cured or not, is whether you don't need the transfusions. Then three patients have been treated with sickle cell disease. They're all free from vascular occlusive, that's the crisis where the sickled red blood cells mess up the vascular system and then you have problems that can be life-threatening. Those patients have been treated for 3-15 months. Then they have nine other patients that have been treated, but there was no efficacy data for them.

On Bluebird side, it was mostly long-term data in Beta-thalassemia. Thirty two patients, 22 from the phase 1/2 study, and 10 from the phase 4 study. Sixty four percent of the phase 1/2 and 90% of those 10 patients in the phase 3 are transfusion independent, so they've treated for quite a while. They've been followed for 19.4 months, all the way up to 69.4 months, so over a year without needing transfusions. It appears that it's a cure for most patients.

Cardina: Excellent. What more information will be needed to show that these experimental gene therapies are safe and effective? What will be the next catalyst?

Orelli: I think Bluebird has enough data that I'm convinced that it works and that it's safe. They probably need a little bit more time, more patients need to go through the whole year before you're going to be fairly convinced. CRISPR obviously needs a lot more data. Once we see that data from those nine patients have been treated, but we don't have efficacy data on them yet. I think that will certainly help the situation.

Cardina: Awesome. Are any of these stocks; Vertex, CRISPR, Bluebird, are any of them a particularly compelling investment today in your opinion?

Orelli: I've not been a big fan of of CRISPR/Cas9 stocks in general, just because I feel like the technology hadn't played itself out, plus CRISPR has some data in can't for cancer, cells that appeared that it's at least working, although there was a death in one of the patients. That's given me more hope that there won't be any snags along the line. A lot of times, if you look at RNAi, RNAi looked impressive in the very beginning, but it took a really long time for Alnylam to develop RNAi and to get a drug on the market, a decade or more. So I think that that's the one issue with CRISPR/Cas9.

Bluebird has definitely proved out gene therapy, but their biggest concern is manufacturing, I think, because you have to develop these for each individual patient. It's not like a traditional manufacturing, where we can just batch up everything. They have to make the cells individually for each individual patient.