Vertex and CRISPR Advance First-In-Kind Therapeutic for SCD

Craig F. Walker/The Boston Globe via Getty

Craig F. Walker/The Boston Globe via Getty

In a potential leap forward for sickle cell disease, Vertex moved closer to launching its one-time treatment for sickle cell disease and transfusion-dependent beta-thalassemia.

Pictured: Vertex Headquarters sign on building/The Boston Globe/Getty Images

In a potential leap forward in treating sickle cell disease (SCD), Vertex Pharmaceuticals moved closer to launching exagamglogene autotemcel (exa-cel)— its one-time treatment for SCD and transfusion-dependent beta-thalassemia (TDT).

In partnership with CRISPR Therapeutics, Vertex completed its rolling submission of a Biologics License Application to the FDA for exa-cel. The companies requested Priority Review.

The therapy is Vertex’s most advanced candidate outside its cystic fibrosis program and is poised to be the first CRISPR-based gene editing therapeutic approved by the FDA. Two ongoing Phase III trials and a long-term study bolster the application.

As a sign of the potential exa-cel has to alter the space, the FDA granted the therapeutic Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations for SCD and TDT.

These exa-cel global regulatory filings are a historic milestone, Carmen Bozic, chief medical officer at Vertex, said in a statement. 

SCD and TDT are caused by mutations in the beta-globin gene, which produces a protein crucial to hemoglobin function. The faulty protein gives rise to abnormal hemoglobin, leading to the trademark anemia seen in both conditions.

With exa-cel, Vertex and CRISPR aim to address the underlying cause of SCD and TDT. The candidate is an autologous and ex vivo gene-edited therapy that uses the CRISPR/Cas9 system to edit a patient’s own hematopoietic stem cells to produce high levels of fetal hemoglobin. This version of the protein is a more-efficient oxygen carrier than adult hemoglobin, and higher levels of the fetal protein can diminish anemia, potentially reducing patients’ need for blood transfusions and easing painful and debilitating episodes in SCD.

Vertex is running five studies examining exa-cel: the Phase I/II/III open-label CLIMB-111 and CLIMB-121 trials, the Phase III open-label CLIMB-141 and CLIMB-151 trials and the long-term open-label CLIMB-131 trial.