Lentiviral Vector & Busulfan Conditioning Agent Cleared In bluebird bio Case
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
The news out of bluebird bio this week has certainly been a boon to the gene therapy industry at large. As I shared on LinkedIn, the LV vector has been redeemed (though, really, it had hardly fallen from grace — except maybe in the views of some overly excitable analysts). As FiercePharma reported, more is now known about the vector’s integration site and, in turn, insertional oncogenesis has been ruled out for these recently diagnoses cancer cases.
bluebird has identified the VAMP4 gene as the site of vector integration. VAMP4 has no known link to the development of AML or processes such as cellular proliferation or genome stability. Bluebird also ran analyses that found no evidence insertion into VAMP4 could affect the regulation or expression of nearby genes, suggesting the therapy is unlikely to have caused the cancer. The suggestion is also supported by the discovery of ‘several well-known genetic mutations and gross chromosomal abnormalities commonly observed in AML’ in the patient.
It goes without saying this is fantastic news, especially for the many other companies working with LV vectors in this space. As you may have noted from some of my previous posts on the topic, a certain amount of hope and optimism is necessary — even if the worst-case scenario should come to pass.
While the vector has taken the spotlight, busulfan should also be getting some attention here, as well. As I shared in a post earlier this week, the conditioning agent was another factor being investigated as a cause of these cancer cases. Given that a number of companies use this conditioning agent prior to administering their ATMPs, there was some concern about the continued use of busulfan for preconditioning. However, as a less widely covered article from Evaluate shared:
There was another vital snippet of information in today’s analyst call on the matter…. On the call, seemingly convened to formalize what the company had controversially told an investor conference two weeks ago, Bluebird’s chief medical officer, Dave Davidson, said vector was present in the AML blasts. This suggested that these cells were not in the patient during preconditioning so, barring a role for residual busulfan, preconditioning was not to blame.
After a tough 2020 in the gene therapy space, this is definitely some cake-worthy news for your Q1’21. In the meantime, while you’re no doubt scraping every bit of spare icing possible from the knife and the sides of the cake box onto your plate (#respect), the EMA is reviewing Zynteglo, bluebird’s currently marketed gene therapy. The agency hopes to conclude its safety investigation by June.