Thread by @DrTiffanyL

Queuing up Dr. Kwiatkowski's of @CHOP_Research giving updated results of the #HGB-206 lentiglobin gene therapy for #sicklecelldisease in today's plenary session at #ASPHO2021. Follow this thread for more 1/n

Why are we talking about gene therapy for #sicklecell. It's estimated <15% of patients have a sibling matched stem cell transplant donor! 2/n

Today's talk is going over group C - eligibility included here. Enrollment has been completed. This is for SS and S beta0 and S beta+ genotypes. 3/n

Lentiglobin modified stem cells are infused after busulfan myeloblative conditioning. There will be 13 years of long term follow-up - 32 have completed infusion thus far with 13 month follow-up.

Complete resolution of the VOE's 6 months after post-lentiglobin treatment in these patients. Of note, you can follow HbA^T87Q is the transduced product - its's in Red here. Median hgb ~11 at 6 months 5/n

Markers of hemolysis significantly improved (to near-normal) - retic, LDH, and total bilirubin. 6/n

Safety data is important for our patients - see this slide for more. No insertional mutagenesis. Many adverse events related to treatment with conditioning regimen. 7/n

There is a CLINICAL HOLD on bluebird bio studies with bb1111 (this lentiglobin therapy). See details of this below -- transfusion dependent anemia is the revised diagnosis for the prior reported MDS case possibly related to the lentiglobin therapy. More information is needed! 8/n

And the conclusions -- Thank you Dr. Kwiatkowski for your summary of this result. Stay tuned for Q&A. 9/n

Q&A thoughts: a) Adol had higher Hgb levels (~13) - still need more numbers to figure out why. b) Busulfan is myeloablative so they anticipated it can/will impact fertility and fert. preservation was offered/taken up by all patients. 10/n

c) Allowed stroke pts initially but subsequently did not allow -- but as of now, no cases of stroke. d) Asking whether the two cases that led to the hold was above busulfan-related known rates. Says it's unclear at this point - concerning that we've seen a couple events. 11/n

e) The patient with AML has checked where integration occurred - in the AML blasts there was insertion in VAMP4 gene (but no known association in this gene with cancer per their review) but this doesn't mean that the gene therapy wasn't the problem - must research more. 12/n

Of note, they are checking every 6 months for insertional data collection and monitoring closely.
Okay, that's it folks! Stay tuned and follow me for more from #ASPHO2021. 13/13 (end!)