A long-anticipated pruning back of the ev vivo gene therapy pipeline for sickle cell disease has arrived with Novartis, Graphite Bio and Sangamo each dropping projects, but some challengers are looking ahead to a future of in vivo approaches to the condition.

The firms’ one-time hemophilia B gene therapy has been approved in the EU just months after a US nod, but concerns remain about its prospects on a market that has seen several setbacks for other gene therapies.

Retiring Office of Tissues and Advanced Therapies’ Director Wilson Bryan expects the expedited pathway will be used more frequently moving forward, but worries that ambiguous confirmatory trial results many years down the line will still leave efficacy questions unanswered.

Pfizer joined Novartis as the market leader in sickle cell disease when it acquired Global Blood Therapeutics last year. The US giant's Oxbryta may now move ahead following a clinical and regulatory setback for the Swiss major's Adakveo.